Cross_talk_ID m6A_Regulator_ID m6A_Target_ID Epigenetic_Regulation_Type_all Epigenetic_Regulator_ID Regulated_Target_ID Downstream Gene ID m6A_Methylation_Regulation Cross_talk_Relationship_1 Cross_talk_Relationship_2 Cross_talk_Relationship_3 Cross_talk_Relationship_4 Crosstalk_Mechanism Cross_talk_Summary Disease_ID PMID Drug_ID M6ACROT03001 REG00007 . Histone modification / Methylation EPIREG00031 EPITAR00201 . . m6A Direct Enhancement Histone modification m6A modification directly impacts histone modification through recruiting histone-associated enzymes "METTL3 interacts physically with the histone 3 lysine 9 (H3K9) tri-methyltransferase SETDB1 and its cofactor TRIM28 to modulate Histone H3 lysine 9 trimethylation (H3K9me3), and is important for their localization to IAPs. Our findings demonstrate that METTL3-catalysed m6A modification of RNA is important for the integrity of IAP heterochromatin in mouse embryonic stem cells, revealing a mechanism of heterochromatin regulation in mammals." . 33505026 . M6ACROT03002 REG00022 . Histone modification / Methylation EPIREG00032 EPITAR00202 . . m6A Direct Enhancement Histone modification m6A modification directly impacts histone modification through recruiting histone-associated enzymes "We demonstrate that the methyltransferase METTL3/METTL14 regulates Histone H3 lysine 9 dimethylation (H3K9me2) modification. We observe a genome-wide correlation between m6A and occupancy by the H3K9me2 demethylase KDM3B, and we find that the m6A reader YTHDC1 physically interacts with and recruits KDM3B to m6A-associated chromatin regions, promoting H3K9me2 demethylation and gene expression. This study establishes a direct link between m6A and dynamic chromatin modification and provides mechanistic insight into the co-transcriptional interplay between RNA modifications and histone modifications." . 32778823 . M6ACROT03003 REG00006 . Histone modification / Methylation EPIREG00032 EPITAR00202 . . m6A Indirect Enhancement Histone modification m6A modification indirectly regulates histone modification through downstream signaling pathways "We demonstrate that the methyltransferase METTL3/METTL14 regulates Histone H3 lysine 9 dimethylation (H3K9me2) modification. We observe a genome-wide correlation between m6A and occupancy by the H3K9me2 demethylase KDM3B, and we find that the m6A reader YTHDC1 physically interacts with and recruits KDM3B to m6A-associated chromatin regions, promoting H3K9me2 demethylation and gene expression. This study establishes a direct link between m6A and dynamic chromatin modification and provides mechanistic insight into the co-transcriptional interplay between RNA modifications and histone modifications." . 32778823 . M6ACROT03004 REG00007 . Histone modification / Methylation EPIREG00032 EPITAR00202 . . m6A Indirect Enhancement Histone modification m6A modification indirectly regulates histone modification through downstream signaling pathways "We demonstrate that the methyltransferase METTL3/METTL14 regulates Histone H3 lysine 9 dimethylation (H3K9me2) modification. We observe a genome-wide correlation between m6A and occupancy by the H3K9me2 demethylase KDM3B, and we find that the m6A reader YTHDC1 physically interacts with and recruits KDM3B to m6A-associated chromatin regions, promoting H3K9me2 demethylation and gene expression. This study establishes a direct link between m6A and dynamic chromatin modification and provides mechanistic insight into the co-transcriptional interplay between RNA modifications and histone modifications." . 32778823 . M6ACROT03005 REG00005 M6ATAR00658 Histone modification / Methylation EPIREG00033 EPITAR00201 EPITAR00183 Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "Expression of ALKBH5 is enhanced during IVD degeneration and NPC senescence, due to decreased KDM4A-mediated Histone H3 lysine 9 trimethylation (H3K9me3) modification. Functionally, ALKBH5 causes NPC senescence by demethylating DNA (cytosine-5)-methyltransferase 3B (DNMT3B) transcripts and in turn promoting its expression via less YTHDF2 recognition and following degradation due to transcript hypomethylation in vitro and in vivo. Increased DNMT3B promotes the development of IVD degeneration and NPC senescence, mechanistically by methylating CpG islands of E4F1 at the promoter region and thus restraining its transcription and expression." M6ADIS0168 35340126 . M6ACROT03006 REG00008 M6ATAR00658 Histone modification / Methylation EPIREG00033 EPITAR00201 EPITAR00183 Down regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "Expression of ALKBH5 is enhanced during IVD degeneration and NPC senescence, due to decreased KDM4A-mediated Histone H3 lysine 9 trimethylation (H3K9me3) modification. Functionally, ALKBH5 causes NPC senescence by demethylating DNA (cytosine-5)-methyltransferase 3B (DNMT3B) transcripts and in turn promoting its expression via less YTHDF2 recognition and following degradation due to transcript hypomethylation in vitro and in vivo. Increased DNMT3B promotes the development of IVD degeneration and NPC senescence, mechanistically by methylating CpG islands of E4F1 at the promoter region and thus restraining its transcription and expression." M6ADIS0168 35340126 . M6ACROT03007 REG00006 M6ATAR01597 Histone modification / Acetylation EPIREG00034 EPITAR00203 . Down regulation m6A Direct Inhibition Histone modification m6A modification impacts directly histone modification through modulating the expression level of histone-associated enzymes "The downregulation of Phosphoprotein associated with glycosphingolipid-enriched microdomains 1 (CBP) and p300 by METTL14 serves as a regulatory mechanism for the modulation of specific histone modifications, namely H3K27me3, Histone H3 lysine 27 acetylation (H3K27ac), and H3K4me3. This regulatory action underscores the role of METTL14 in epigenetic control through the influence of m6A RNA methylation on histone modification patterns." . 29335608 . M6ACROT03008 REG00006 M6ATAR01598 Histone modification / Acetylation EPIREG00035 EPITAR00203 . Down regulation m6A Direct Inhibition Histone modification m6A modification impacts directly histone modification through modulating the expression level of histone-associated enzymes "The downregulation of CBP and Histone acetyltransferase p300 (P300) by METTL14 serves as a regulatory mechanism for the modulation of specific histone modifications, namely H3K27me3, Histone H3 lysine 27 acetylation (H3K27ac), and H3K4me3. This regulatory action underscores the role of METTL14 in epigenetic control through the influence of m6A RNA methylation on histone modification patterns." . 29335608 . M6ACROT03009 REG00006 M6ATAR01597 Histone modification / Methylation EPIREG00034 EPITAR00204 . Down regulation m6A Direct Inhibition Histone modification m6A modification impacts directly histone modification through modulating the expression level of histone-associated enzymes "The downregulation of Phosphoprotein associated with glycosphingolipid-enriched microdomains 1 (CBP) and p300 by METTL14 serves as a regulatory mechanism for the modulation of specific histone modifications, namely H3K27me3, H3K27ac, and Histone H3 lysine 4 trimethylation (H3K4me3). This regulatory action underscores the role of METTL14 in epigenetic control through the influence of m6A RNA methylation on histone modification patterns." . 29335608 . M6ACROT03010 REG00006 M6ATAR01598 Histone modification / Methylation EPIREG00035 EPITAR00204 . Down regulation m6A Direct Inhibition Histone modification m6A modification impacts directly histone modification through modulating the expression level of histone-associated enzymes "The downregulation of CBP and Histone acetyltransferase p300 (P300) by METTL14 serves as a regulatory mechanism for the modulation of specific histone modifications, namely H3K27me3, H3K27ac, and Histone H3 lysine 4 trimethylation (H3K4me3). This regulatory action underscores the role of METTL14 in epigenetic control through the influence of m6A RNA methylation on histone modification patterns." . 29335608 . M6ACROT03011 REG00006 M6ATAR01597 Histone modification / Methylation EPIREG00034 EPITAR00205 . Down regulation m6A Direct Inhibition Histone modification m6A modification impacts directly histone modification through modulating the expression level of histone-associated enzymes "The downregulation of Phosphoprotein associated with glycosphingolipid-enriched microdomains 1 (CBP) and p300 by METTL14 serves as a regulatory mechanism for the modulation of specific histone modifications, namely Histone H3 lysine 27 trimethylation (H3K27me3), H3K27ac, and H3K4me3. This regulatory action underscores the role of METTL14 in epigenetic control through the influence of m6A RNA methylation on histone modification patterns." . 29335608 . M6ACROT03012 REG00006 M6ATAR01598 Histone modification / Methylation EPIREG00035 EPITAR00205 . Down regulation m6A Direct Inhibition Histone modification m6A modification impacts directly histone modification through modulating the expression level of histone-associated enzymes "The downregulation of CBP and Histone acetyltransferase p300 (P300) by METTL14 serves as a regulatory mechanism for the modulation of specific histone modifications, namely Histone H3 lysine 27 trimethylation (H3K27me3), H3K27ac, and H3K4me3. This regulatory action underscores the role of METTL14 in epigenetic control through the influence of m6A RNA methylation on histone modification patterns." . 29335608 . M6ACROT03013 REG00007 M6ATAR00249 Histone modification / Methylation EPIREG00036 EPITAR00205 . Up regulation m6A Direct Enhancement Histone modification m6A modification impacts directly histone modification through modulating the expression level of histone-associated enzymes "m6A was present on the transcripts of histone methyltransferase Histone-lysine N-methyltransferase EZH2 (EZH2), and its reduction upon METTL3 knockdown decreased both Ezh2 protein expression and consequent Histone H3 lysine 27 trimethylation (H3K27me3) levels. The defects of neurogenesis and neuronal development induced by Mettl3-depletion could be rescued by Ezh2 overexpression. Collectively, our results uncover a crosstalk between RNA and histone modifications and indicate that Mettl3-mediated m6A modification plays an important role in regulating neurogenesis and neuronal development through modulating Ezh2." . 31154015 . M6ACROT03014 REG00008 M6ATAR01264 Histone modification / Methylation EPIREG00037 EPITAR00205 EPITAR00170 Down regulation m6A Direct Inhibition Histone modification m6A modification impacts directly histone modification through modulating the expression level of histone-associated enzymes "The mRNA of Lysine-specific demethylase 6B (KDM6B) was m6A-modified by METTL3/METTL14 and its decay mediated by YTHDF2. YTHDF2 deficiency stabilized KDM6B to promote Histone H3 lysine 27 trimethylation (H3K27me3) demethylation of multiple proinflammatory cytokines and subsequently enhanced their transcription. Knockout (KO) of YTHDF2, an m6A reader, markedly enhanced demethylation of H3K27me3 on the promoters of proinflammatory cytokines (e.g., IL6 and IL-12B). Furthermore, we identified H3K27me3 as a barrier for m6A modification during transcription. KDM6B recruits the m6A methyltransferase complex to facilitate the methylation of m6A in transcribing mRNA by removing adjacent H3K27me3 barriers. These results revealed cross-talk between m6A and H3K27me3 during bacterial infection, which has broader implications for deciphering epitranscriptomics in immune homeostasis." M6ADIS0125 32875102 . M6ACROT03015 REG00007 M6ATAR01264 Histone modification / Methylation EPIREG00037 EPITAR00205 EPITAR00170 Down regulation m6A Direct Inhibition Histone modification m6A modification impacts directly histone modification through modulating the expression level of histone-associated enzymes "The mRNA of Lysine-specific demethylase 6B (KDM6B) was m6A-modified by METTL3/METTL14 and its decay mediated by YTHDF2. YTHDF2 deficiency stabilized KDM6B to promote Histone H3 lysine 27 trimethylation (H3K27me3) demethylation of multiple proinflammatory cytokines and subsequently enhanced their transcription. Knockout (KO) of YTHDF2, an m6A reader, markedly enhanced demethylation of H3K27me3 on the promoters of proinflammatory cytokines (e.g., IL6 and IL-12B). Furthermore, we identified H3K27me3 as a barrier for m6A modification during transcription. KDM6B recruits the m6A methyltransferase complex to facilitate the methylation of m6A in transcribing mRNA by removing adjacent H3K27me3 barriers. These results revealed cross-talk between m6A and H3K27me3 during bacterial infection, which has broader implications for deciphering epitranscriptomics in immune homeostasis." M6ADIS0125 32875102 . M6ACROT03016 REG00006 M6ATAR01264 Histone modification / Methylation EPIREG00037 EPITAR00205 EPITAR00170 Down regulation m6A Direct Inhibition Histone modification m6A modification impacts directly histone modification through modulating the expression level of histone-associated enzymes "The mRNA of Lysine-specific demethylase 6B (KDM6B) was m6A-modified by METTL3/METTL14 and its decay mediated by YTHDF2. YTHDF2 deficiency stabilized KDM6B to promote Histone H3 lysine 27 trimethylation (H3K27me3) demethylation of multiple proinflammatory cytokines and subsequently enhanced their transcription. Knockout (KO) of YTHDF2, an m6A reader, markedly enhanced demethylation of H3K27me3 on the promoters of proinflammatory cytokines (e.g., IL6 and IL-12B). Furthermore, we identified H3K27me3 as a barrier for m6A modification during transcription. KDM6B recruits the m6A methyltransferase complex to facilitate the methylation of m6A in transcribing mRNA by removing adjacent H3K27me3 barriers. These results revealed cross-talk between m6A and H3K27me3 during bacterial infection, which has broader implications for deciphering epitranscriptomics in immune homeostasis." M6ADIS0125 32875102 . M6ACROT03017 REG00009 M6ATAR00529 Histone modification / Methylation EPIREG00037 EPITAR00205 EPITAR00170 . Histone modification Direct Enhancement m6A Histone modification directly impacts m6A modification through recruiting m6A regulator "Knockout (KO) of YTHDF2, an m6A reader, markedly enhanced demethylation of Histone H3 lysine 27 trimethylation (H3K27me3) on the promoters of proinflammatory cytokines (e.g., Interleukin-6 (IL-6) and IL-12B). Furthermore, we identified H3K27me3 as a barrier for m6A modification during transcription. KDM6B recruits the m6A methyltransferase complex (METTL3/METTL14/WTAP) to facilitate the methylation of m6A in transcribing mRNA by removing adjacent H3K27me3 barriers. These results revealed cross-talk between m6A and H3K27me3 during bacterial infection, which has broader implications for deciphering epitranscriptomics in immune homeostasis." M6ADIS0125 32875102 . M6ACROT03018 REG00007 M6ATAR00529 Histone modification / Methylation EPIREG00037 EPITAR00205 EPITAR00170 . Histone modification Direct Enhancement m6A Histone modification directly impacts m6A modification through recruiting m6A regulator "Knockout (KO) of YTHDF2, an m6A reader, markedly enhanced demethylation of Histone H3 lysine 27 trimethylation (H3K27me3) on the promoters of proinflammatory cytokines (e.g., Interleukin-6 (IL-6) and IL-12B). Furthermore, we identified H3K27me3 as a barrier for m6A modification during transcription. KDM6B recruits the m6A methyltransferase complex (METTL3/METTL14/WTAP) to facilitate the methylation of m6A in transcribing mRNA by removing adjacent H3K27me3 barriers. These results revealed cross-talk between m6A and H3K27me3 during bacterial infection, which has broader implications for deciphering epitranscriptomics in immune homeostasis." M6ADIS0125 32875102 . M6ACROT03019 REG00006 M6ATAR00529 Histone modification / Methylation EPIREG00037 EPITAR00205 EPITAR00170 . Histone modification Direct Enhancement m6A Histone modification directly impacts m6A modification through recruiting m6A regulator "Knockout (KO) of YTHDF2, an m6A reader, markedly enhanced demethylation of Histone H3 lysine 27 trimethylation (H3K27me3) on the promoters of proinflammatory cytokines (e.g., Interleukin-6 (IL-6) and IL-12B). Furthermore, we identified H3K27me3 as a barrier for m6A modification during transcription. KDM6B recruits the m6A methyltransferase complex (METTL3/METTL14/WTAP) to facilitate the methylation of m6A in transcribing mRNA by removing adjacent H3K27me3 barriers. These results revealed cross-talk between m6A and H3K27me3 during bacterial infection, which has broader implications for deciphering epitranscriptomics in immune homeostasis." M6ADIS0125 32875102 . M6ACROT03020 REG00005 M6ATAR00443 Histone modification / Methylation EPIREG00038 EPITAR00201 EPITAR00183 Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "KDM4C regulates ALKBH5 expression via increasing chromatin accessibility of ALKBH5 locus, by reducing Histone H3 lysine 9 trimethylation (H3K9me3) levels and promoting recruitment of MYB and Pol II. Moreover, ALKBH5 affects mRNA stability of receptor tyrosine kinase Tyrosine-protein kinase receptor UFO (AXL) in an m6A-dependent way." M6ADIS0046 32402251 . M6ACROT03021 REG00005 M6ATAR00443 Histone modification / Methylation EPIREG00039 EPITAR00204 EPITAR00183 Up regulation Histone modification Direct Inhibition m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "KMT2A regulates ALKBH5 expression via decreasing chromatin accessibility of ALKBH5 locus, by increasing Histone H3 lysine 4 trimethylation (H3K4me3) levels and inhibiting recruitment of MYB and Pol II. Moreover, ALKBH5 affects mRNA stability of receptor tyrosine kinase Tyrosine-protein kinase receptor UFO (AXL) in an m6A-dependent way." M6ADIS0046 32402251 . M6ACROT03022 REG00005 M6ATAR00443 Histone modification / Methylation EPIREG00040 EPITAR00204 EPITAR00183 Up regulation Histone modification Direct Inhibition m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "KMT2C regulates ALKBH5 expression via decreasing chromatin accessibility of ALKBH5 locus, by increasing Histone H3 lysine 4 trimethylation (H3K4me3) levels and inhibiting recruitment of MYB and Pol II. Moreover, ALKBH5 affects mRNA stability of receptor tyrosine kinase Tyrosine-protein kinase receptor UFO (AXL) in an m6A-dependent way." M6ADIS0046 32402251 . M6ACROT03023 REG00005 M6ATAR00443 Histone modification / Methylation EPIREG00041 EPITAR00201 EPITAR00183 Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "KDM4B regulates ALKBH5 expression via increasing chromatin accessibility of ALKBH5 locus, by reducing Histone H3 lysine 9 trimethylation (H3K9me3) levels and promoting recruitment of MYB and Pol II. Moreover, ALKBH5 affects mRNA stability of receptor tyrosine kinase Tyrosine-protein kinase receptor UFO (AXL) in an m6A-dependent way." M6ADIS0046 32402251 . M6ACROT03024 REG00005 M6ATAR00443 Histone modification / Methylation EPIREG00042 EPITAR00201 EPITAR00183 Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "JMJD1C regulates ALKBH5 expression via increasing chromatin accessibility of ALKBH5 locus, by reducing Histone H3 lysine 9 trimethylation (H3K9me3) levels and promoting recruitment of MYB and Pol II. Moreover, ALKBH5 affects mRNA stability of receptor tyrosine kinase Tyrosine-protein kinase receptor UFO (AXL) in an m6A-dependent way." M6ADIS0046 32402251 . M6ACROT03025 REG00006 . Histone modification / Methylation EPIREG00043 EPITAR00206 . Up regulation Histone modification Direct Enhancement m6A Histone modification directly impacts m6A modification through recruiting m6A regulator "The identification of the SETD2-mediated histone mark Histone H3 lysine 36 trimethylation (H3K36me3) as a determinant of m6A RNA modification via Methyltransferase complex (METTL14, METTL3 and WTAP) reveals a cross-talk between histone modification and RNA methylation, and adds another layer of complexity to the control of gene expression in normal and pathological biological processes." . 30867593 . M6ACROT03026 REG00007 . Histone modification / Methylation EPIREG00043 EPITAR00206 . Up regulation Histone modification Direct Enhancement m6A Histone modification directly impacts m6A modification through recruiting m6A regulator "The identification of the SETD2-mediated histone mark Histone H3 lysine 36 trimethylation (H3K36me3) as a determinant of m6A RNA modification via Methyltransferase complex (METTL14, METTL3 and WTAP) reveals a cross-talk between histone modification and RNA methylation, and adds another layer of complexity to the control of gene expression in normal and pathological biological processes." . 30867593 . M6ACROT03027 REG00006 M6ATAR01599 Histone modification / Methylation EPIREG00044 EPITAR00204 EPITAR00553 Up regulation m6A Direct Enhancement Histone modification m6A modification impacts directly histone modification through modulating the expression level of histone-associated enzymes "Among validating hits are genes coding for the N6-methyladenosine (m6A) mRNA methyltransferase (MTase) complex, including, METTL14, METTL3, and WTAP. We demonstrate that m6A MTase activity promotes erythroid gene expression programs through selective translation of ~300 m6A marked mRNAs, including those coding for Histone-lysine N-methyltransferase SETD1A (SETD1A), SETD1B and KTM2D. Remarkably, loss of m6A marks results in dramatic loss of Histone H3 lysine 4 trimethylation (H3K4me3) marks across key erythroid-specific KLF1 transcriptional targets" . 31601799 . M6ACROT03028 REG00006 M6ATAR01600 Histone modification / Methylation EPIREG00045 EPITAR00204 EPITAR00553 Up regulation m6A Direct Enhancement Histone modification m6A modification impacts directly histone modification through modulating the expression level of histone-associated enzymes "Among validating hits are genes coding for the N6-methyladenosine (m6A) mRNA methyltransferase (MTase) complex, including, METTL14, METTL3, and WTAP. We demonstrate that m6A MTase activity promotes erythroid gene expression programs through selective translation of ~300 m6A marked mRNAs, including those coding for SETD1A, Histone-lysine N-methyltransferase SETD1B (SETD1B) and KTM2D. Remarkably, loss of m6A marks results in dramatic loss of Histone H3 lysine 4 trimethylation (H3K4me3) marks across key erythroid-specific KLF1 transcriptional targets" . 31601799 . M6ACROT03029 REG00006 M6ATAR01601 Histone modification / Methylation EPIREG00046 EPITAR00204 EPITAR00553 Up regulation m6A Direct Enhancement Histone modification m6A modification impacts directly histone modification through modulating the expression level of histone-associated enzymes "Among validating hits are genes coding for the N6-methyladenosine (m6A) mRNA methyltransferase (MTase) complex, including, METTL14, METTL3, and WTAP. We demonstrate that m6A MTase activity promotes erythroid gene expression programs through selective translation of ~300 m6A marked mRNAs, including those coding for SETD1A, SETD1B and Histone-lysine N-methyltransferase 2D (KMT2D). Remarkably, loss of m6A marks results in dramatic loss of Histone H3 lysine 4 trimethylation (H3K4me3) marks across key erythroid-specific KLF1 transcriptional targets" . 31601799 . M6ACROT03030 REG00007 M6ATAR01599 Histone modification / Methylation EPIREG00044 EPITAR00204 EPITAR00553 Up regulation m6A Direct Enhancement Histone modification m6A modification impacts directly histone modification through modulating the expression level of histone-associated enzymes "Among validating hits are genes coding for the N6-methyladenosine (m6A) mRNA methyltransferase (MTase) complex, including, METTL14, METTL3, and WTAP. We demonstrate that m6A MTase activity promotes erythroid gene expression programs through selective translation of ~300 m6A marked mRNAs, including those coding for Histone-lysine N-methyltransferase SETD1A (SETD1A), SETD1B and KTM2D. Remarkably, loss of m6A marks results in dramatic loss of Histone H3 lysine 4 trimethylation (H3K4me3) marks across key erythroid-specific KLF1 transcriptional targets" . 31601799 . M6ACROT03031 REG00007 M6ATAR01600 Histone modification / Methylation EPIREG00045 EPITAR00204 EPITAR00553 Up regulation m6A Direct Enhancement Histone modification m6A modification impacts directly histone modification through modulating the expression level of histone-associated enzymes "Among validating hits are genes coding for the N6-methyladenosine (m6A) mRNA methyltransferase (MTase) complex, including, METTL14, METTL3, and WTAP. We demonstrate that m6A MTase activity promotes erythroid gene expression programs through selective translation of ~300 m6A marked mRNAs, including those coding for SETD1A, Histone-lysine N-methyltransferase SETD1B (SETD1B) and KTM2D. Remarkably, loss of m6A marks results in dramatic loss of Histone H3 lysine 4 trimethylation (H3K4me3) marks across key erythroid-specific KLF1 transcriptional targets" . 31601799 . M6ACROT03032 REG00007 M6ATAR01601 Histone modification / Methylation EPIREG00046 EPITAR00204 EPITAR00553 Up regulation m6A Direct Enhancement Histone modification m6A modification impacts directly histone modification through modulating the expression level of histone-associated enzymes "Among validating hits are genes coding for the N6-methyladenosine (m6A) mRNA methyltransferase (MTase) complex, including, METTL14, METTL3, and WTAP. We demonstrate that m6A MTase activity promotes erythroid gene expression programs through selective translation of ~300 m6A marked mRNAs, including those coding for SETD1A, SETD1B and Histone-lysine N-methyltransferase 2D (KMT2D). Remarkably, loss of m6A marks results in dramatic loss of Histone H3 lysine 4 trimethylation (H3K4me3) marks across key erythroid-specific KLF1 transcriptional targets" . 31601799 . M6ACROT03033 REG00009 M6ATAR01599 Histone modification / Methylation EPIREG00044 EPITAR00204 EPITAR00553 Up regulation m6A Direct Enhancement Histone modification m6A modification impacts directly histone modification through modulating the expression level of histone-associated enzymes "Among validating hits are genes coding for the N6-methyladenosine (m6A) mRNA methyltransferase (MTase) complex, including, METTL14, METTL3, and WTAP. We demonstrate that m6A MTase activity promotes erythroid gene expression programs through selective translation of ~300 m6A marked mRNAs, including those coding for Histone-lysine N-methyltransferase SETD1A (SETD1A), SETD1B and KTM2D. Remarkably, loss of m6A marks results in dramatic loss of Histone H3 lysine 4 trimethylation (H3K4me3) marks across key erythroid-specific KLF1 transcriptional targets" . 31601799 . M6ACROT03034 REG00009 M6ATAR01600 Histone modification / Methylation EPIREG00045 EPITAR00204 EPITAR00553 Up regulation m6A Direct Enhancement Histone modification m6A modification impacts directly histone modification through modulating the expression level of histone-associated enzymes "Among validating hits are genes coding for the N6-methyladenosine (m6A) mRNA methyltransferase (MTase) complex, including, METTL14, METTL3, and WTAP. We demonstrate that m6A MTase activity promotes erythroid gene expression programs through selective translation of ~300 m6A marked mRNAs, including those coding for SETD1A, Histone-lysine N-methyltransferase SETD1B (SETD1B) and KTM2D. Remarkably, loss of m6A marks results in dramatic loss of Histone H3 lysine 4 trimethylation (H3K4me3) marks across key erythroid-specific KLF1 transcriptional targets" . 31601799 . M6ACROT03035 REG00009 M6ATAR01601 Histone modification / Methylation EPIREG00046 EPITAR00204 EPITAR00553 Up regulation m6A Direct Enhancement Histone modification m6A modification impacts directly histone modification through modulating the expression level of histone-associated enzymes "Among validating hits are genes coding for the N6-methyladenosine (m6A) mRNA methyltransferase (MTase) complex, including, METTL14, METTL3, and WTAP. We demonstrate that m6A MTase activity promotes erythroid gene expression programs through selective translation of ~300 m6A marked mRNAs, including those coding for SETD1A, SETD1B and Histone-lysine N-methyltransferase 2D (KMT2D). Remarkably, loss of m6A marks results in dramatic loss of Histone H3 lysine 4 trimethylation (H3K4me3) marks across key erythroid-specific KLF1 transcriptional targets" . 31601799 . M6ACROT03036 REG00006 M6ATAR00405 Histone modification / Methylation EPIREG00047 EPITAR00204 EPITAR00195 Down regulation Histone modification Direct Inhibition m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "Both the univariate and multivariate Cox regression analysis indicated that METTL14 was an independent prognostic factor in CRC. Moreover, KDM5C-mediated demethylation of Histone H3 lysine 36 trimethylation (H3K36me3) in the promoter of METTL14 inhibited METTL14 transcription. METTL14-mediated Transcription factor SOX-4 (SOX4) mRNA degradation relied on the YTHDF2-dependent pathway." M6ADIS0059 32552762 . M6ACROT03037 REG00008 M6ATAR00405 Histone modification / Methylation EPIREG00047 EPITAR00204 EPITAR00195 Down regulation Histone modification Indirect Inhibition m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "Both the univariate and multivariate Cox regression analysis indicated that METTL14 was an independent prognostic factor in CRC. Moreover, KDM5C-mediated demethylation of Histone H3 lysine 36 trimethylation (H3K36me3) in the promoter of METTL14 inhibited METTL14 transcription. METTL14-mediated Transcription factor SOX-4 (SOX4) mRNA degradation relied on the YTHDF2-dependent pathway." M6ADIS0059 32552762 . M6ACROT03038 REG00007 M6ATAR00249 Histone modification / Acetylation EPIREG00036 EPITAR00203 EPITAR00027 Down regulation m6A Direct Inhibition Histone modification m6A modification impacts directly histone modification through modulating the expression level of histone-associated enzymes "METTL3 is required to maintain the features of GBM stem cells. When combined with TMZ, METTL3 silencing suppressed orthotopic TMZ-resistant xenograft growth in a cooperative manner. Mechanistically, TMZ induced a SOX4-mediated increase in chromatin accessibility at the METTL3 locus by promoting Histone H3 lysine 27 acetylation (H3K27ac) levels and recruiting RNA polymerase II. Moreover, METTL3 depletion affected the deposition of m6A on histone modification-related gene transcripts, such as Histone-lysine N-methyltransferase EZH2 (EZH2), leading to nonsense-mediated mRNA decay." M6ADIS0001 34586728 M6ADRUG0010 M6ACROT03039 REG00007 M6ATAR00249 Histone modification / Acetylation EPIREG00036 EPITAR00203 EPITAR00027 Down regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "METTL3 is required to maintain the features of GBM stem cells. When combined with TMZ, METTL3 silencing suppressed orthotopic TMZ-resistant xenograft growth in a cooperative manner. Mechanistically, TMZ induced a SOX4-mediated increase in chromatin accessibility at the METTL3 locus by promoting Histone H3 lysine 27 acetylation (H3K27ac) levels and recruiting RNA polymerase II. Moreover, METTL3 depletion affected the deposition of m6A on histone modification-related gene transcripts, such as Histone-lysine N-methyltransferase EZH2 (EZH2), leading to nonsense-mediated mRNA decay." M6ADIS0001 34586728 M6ADRUG0010 M6ACROT03040 REG00005 M6ATAR00501 Histone modification / Ubiquitination EPIREG00048 EPITAR00207 . Up regulation m6A Direct Enhancement Histone modification m6A modification impacts directly histone modification through modulating the expression level of histone-associated enzymes "RNA demethylase ALKBH5 upregulates Ubiquitin carboxyl-terminal hydrolase 22 (USP22) and RNF40 to inhibit Histone H2A lysine 119 ubiquitination (H2AK119ub) and induces expression of key replication and DNA repair-associated genes, driving osteosarcoma progression." M6ADIS0051 35303054 . M6ACROT03041 REG00005 M6ATAR00502 Histone modification / Ubiquitination EPIREG00049 EPITAR00207 . Up regulation m6A Direct Enhancement Histone modification m6A modification impacts directly histone modification through modulating the expression level of histone-associated enzymes "RNA demethylase ALKBH5 upregulates USP22 and E3 ubiquitin-protein ligase BRE1B (RNF40) to inhibit Histone H2A lysine 119 ubiquitination (H2AK119ub) and induces expression of key replication and DNA repair-associated genes, driving osteosarcoma progression." M6ADIS0051 35303054 . M6ACROT03042 REG00007 M6ATAR01602 Histone modification / Methylation EPIREG00043 EPITAR00206 EPITAR00465 Down regulation m6A Direct Inhibition Histone modification m6A modification impacts directly histone modification through modulating the expression level of histone-associated enzymes "METTL3 knockdown also reduced VGF expression by increasing Histone H3 lysine 36 trimethylation (H3K36me3) modification at the VGF promoter. Further research revealed that METTL3 knockdown upregulated the expression of histone methylase Histone-lysine N-methyltransferase SETD2 (SETD2), the major H3K36me3 methyltransferase, by methylating the m6A site in the 3'UTR of SETD2 mRNA in LUAD cells." M6ADIS0007 37742030 . M6ACROT03043 REG00023 M6ATAR00375 Histone modification / Methylation EPIREG00050 EPITAR00205 . Down regulation m6A Indirect Enhancement Histone modification m6A modification indirectly regulates histone modification through downstream signaling pathways We discovered that YTHDC2 inhibition increased the expression of Mutated in multiple advanced cancers 1 (PTEN) while it decreased the expression of the PRC2 component SUZ12 and the levels of the histone modification Histone H3 lysine 27 trimethylation (H3K27me3). M6ADIS0308 38190286 . M6ACROT03044 REG00007 M6ATAR00200 Histone modification / Lactylation EPIREG00051 EPITAR00208 EPITAR00027 Up regulation Histone modification Direct Enhancement m6A Histone modification directly impacts m6A modification through modulating the level of m6A regulator "LDHA knockdown-mediated inhibition of endogenous Histone H3 lysine 18 lactylation (H3K18la) suppressed osteogenic differentiation, a phenotype that was rescued by METTL3 overexpression. In conclusion, this study elucidates that histone lactylation-mediated upregulation of METTL3 promotes OLF progression through IGF2BP1-dependent m6A methylation of Bone morphogenetic protein 2 (BMP2), providing novel insights into potential therapeutic strategies for OLF management." M6ADIS0113 40133819 . M6ACROT03045 REG00012 M6ATAR00200 Histone modification / Lactylation EPIREG00051 EPITAR00208 EPITAR00027 Up regulation Histone modification Indirect Enhancement m6A Histone modification indirectly regulates m6A modification through downstream signaling pathways "LDHA knockdown-mediated inhibition of endogenous Histone H3 lysine 18 lactylation (H3K18la) suppressed osteogenic differentiation, a phenotype that was rescued by METTL3 overexpression. In conclusion, this study elucidates that histone lactylation-mediated upregulation of METTL3 promotes OLF progression through IGF2BP1-dependent m6A methylation of Bone morphogenetic protein 2 (BMP2), providing novel insights into potential therapeutic strategies for OLF management." M6ADIS0113 40133819 . M6ACROT03046 REG00017 M6ATAR01602 Histone modification / Methylation EPIREG00043 EPITAR00206 EPITAR00466 Down regulation m6A Direct Inhibition Histone modification m6A modification impacts directly histone modification through modulating the expression level of histone-associated enzymes "Furthermore, through the MeRIP-qPCR and dual-luciferase reporter assays, we found that knocking down METTL16 reduced the m6A modification level of the UBXN1 coding sequence in GC. Interestingly, the silencing of METTL16 upregulated the expression of the major Histone H3 lysine 36 trimethylation (H3K36me3) methyltransferase Histone-lysine N-methyltransferase SETD2 (SETD2) in GC cells by methylating the m6A site in the mRNA coding sequence of SETD2 and also downregulated UBXN1 expression by promoting H3K36me3 modification at the UBXN1 promoter." M6ADIS0057 40095756 . M6ACROT03047 REG00008 M6ATAR00364 Histone modification / Lactylation EPIREG00051 EPITAR00208 EPITAR00232 Down regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "Here, we show histone lactylation is elevated in tumors and is associated with poor prognosis of ocular melanoma. Target correction of aberrant histone lactylation triggers therapeutic efficacy both in vitro and in vivo. Mechanistically, LDHA/LDHB-mediated Histone H3 lysine 18 lactylation (H3K18la) contributes to tumorigenesis by facilitating YTHDF2 expression. Moreover, YTHDF2 recognizes the m6A modified Period circadian protein homolog 1 (PER1) and TP53 mRNAs and promotes their degradation, which accelerates tumorigenesis of ocular melanoma." M6ADIS0072 33726814 . M6ACROT03048 REG00008 M6ATAR00364 Histone modification / Lactylation EPIREG00052 EPITAR00208 EPITAR00232 Down regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "Here, we show histone lactylation is elevated in tumors and is associated with poor prognosis of ocular melanoma. Target correction of aberrant histone lactylation triggers therapeutic efficacy both in vitro and in vivo. Mechanistically, LDHA/LDHB-mediated Histone H3 lysine 18 lactylation (H3K18la) contributes to tumorigenesis by facilitating YTHDF2 expression. Moreover, YTHDF2 recognizes the m6A modified Period circadian protein homolog 1 (PER1) and TP53 mRNAs and promotes their degradation, which accelerates tumorigenesis of ocular melanoma." M6ADIS0072 33726814 . M6ACROT03049 REG00008 M6ATAR00356 Histone modification / Lactylation EPIREG00051 EPITAR00208 EPITAR00232 Down regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "Here, we show histone lactylation is elevated in tumors and is associated with poor prognosis of ocular melanoma. Target correction of aberrant histone lactylation triggers therapeutic efficacy both in vitro and in vivo. Mechanistically, LDHA/LDHB-mediated Histone H3 lysine 18 lactylation (H3K18la) contributes to tumorigenesis by facilitating YTHDF2 expression. Moreover, YTHDF2 recognizes the m6A modified PER1 and Cellular tumor antigen p53 (TP53/p53) mRNAs and promotes their degradation, which accelerates tumorigenesis of ocular melanoma." M6ADIS0072 33726814 . M6ACROT03050 REG00008 M6ATAR00356 Histone modification / Lactylation EPIREG00052 EPITAR00208 EPITAR00232 Down regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "Here, we show histone lactylation is elevated in tumors and is associated with poor prognosis of ocular melanoma. Target correction of aberrant histone lactylation triggers therapeutic efficacy both in vitro and in vivo. Mechanistically, LDHA/LDHB-mediated Histone H3 lysine 18 lactylation (H3K18la) contributes to tumorigenesis by facilitating YTHDF2 expression. Moreover, YTHDF2 recognizes the m6A modified PER1 and Cellular tumor antigen p53 (TP53/p53) mRNAs and promotes their degradation, which accelerates tumorigenesis of ocular melanoma." M6ADIS0072 33726814 . M6ACROT03051 REG00006 M6ATAR00619 Histone modification / Acetylation EPIREG00091 EPITAR00203 EPITAR00195 Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "First, we found that ocular melanoma cells presented vulnerability towards HDACis. HDACis triggered the elevation of m6A RNA modification in ocular melanoma. Further studies revealed that METTL14 served as a downstream candidate for HDACis. METTL14 was silenced by the hypo-histone acetylation status, whereas HDACi restored the normal histone acetylation (Histone H3 lysine 27 acetylation (H3K27ac)/H3K9ac) level of METTL14, thereby inducing its expression. Subsequently, METTL14 served as a tumor suppressor by promoting the expression of Protocadherin Fat 4 (FAT4), a tumor suppressor, in a m6A-YTHDF1-dependent manner. Taken together, we found that HDACi restored the histone acetylation level of METTL14 and subsequently elicited METTL14-mediated m6A modification in tumorigenesis." M6ADIS0072 37466203 . M6ACROT03052 REG00006 M6ATAR00619 Histone modification / Acetylation EPIREG00091 EPITAR00209 EPITAR00195 Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "First, we found that ocular melanoma cells presented vulnerability towards HDACis. HDACis triggered the elevation of m6A RNA modification in ocular melanoma. Further studies revealed that METTL14 served as a downstream candidate for HDACis. METTL14 was silenced by the hypo-histone acetylation status, whereas HDACi restored the normal histone acetylation (H3K27ac/Histone H3 lysine 9 acetylation (H3K9ac)) level of METTL14, thereby inducing its expression. Subsequently, METTL14 served as a tumor suppressor by promoting the expression of Protocadherin Fat 4 (FAT4), a tumor suppressor, in a m6A-YTHDF1-dependent manner. Taken together, we found that HDACi restored the histone acetylation level of METTL14 and subsequently elicited METTL14-mediated m6A modification in tumorigenesis." M6ADIS0072 37466203 . M6ACROT03053 REG00024 M6ATAR00619 Histone modification / Acetylation EPIREG00091 EPITAR00203 EPITAR00195 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "First, we found that ocular melanoma cells presented vulnerability towards HDACis. HDACis triggered the elevation of m6A RNA modification in ocular melanoma. Further studies revealed that METTL14 served as a downstream candidate for HDACis. METTL14 was silenced by the hypo-histone acetylation status, whereas HDACi restored the normal histone acetylation (Histone H3 lysine 27 acetylation (H3K27ac)/H3K9ac) level of METTL14, thereby inducing its expression. Subsequently, METTL14 served as a tumor suppressor by promoting the expression of Protocadherin Fat 4 (FAT4), a tumor suppressor, in a m6A-YTHDF1-dependent manner. Taken together, we found that HDACi restored the histone acetylation level of METTL14 and subsequently elicited METTL14-mediated m6A modification in tumorigenesis." M6ADIS0072 37466203 . M6ACROT03054 REG00024 M6ATAR00619 Histone modification / Acetylation EPIREG00091 EPITAR00209 EPITAR00195 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "First, we found that ocular melanoma cells presented vulnerability towards HDACis. HDACis triggered the elevation of m6A RNA modification in ocular melanoma. Further studies revealed that METTL14 served as a downstream candidate for HDACis. METTL14 was silenced by the hypo-histone acetylation status, whereas HDACi restored the normal histone acetylation (H3K27ac/Histone H3 lysine 9 acetylation (H3K9ac)) level of METTL14, thereby inducing its expression. Subsequently, METTL14 served as a tumor suppressor by promoting the expression of Protocadherin Fat 4 (FAT4), a tumor suppressor, in a m6A-YTHDF1-dependent manner. Taken together, we found that HDACi restored the histone acetylation level of METTL14 and subsequently elicited METTL14-mediated m6A modification in tumorigenesis." M6ADIS0072 37466203 . M6ACROT03055 REG00006 . Histone modification / Methylation EPIREG00050 EPITAR00205 . . m6A Direct Enhancement Histone modification m6A modification directly impacts histone modification through recruiting histone-associated enzymes "METTL14 enhances Histone H3 lysine 27 trimethylation (H3K27me3) and reduces H3K4me3 by interacting with and probably recruiting the H3K27 methyltransferase polycomb repressive complex 2 (PRC2) and H3K4 demethylase KDM5B to chromatin. Our findings identify an METTL3-independent role of METTL14 in maintaining the integrity of bivalent domains in mESCs, thus indicating a mechanism of bivalent domain regulation in mammals." . 37314930 . M6ACROT03056 REG00006 . Histone modification / Methylation EPIREG00053 EPITAR00204 . . m6A Direct Enhancement Histone modification m6A modification directly impacts histone modification through recruiting histone-associated enzymes "METTL14 enhances H3K27me3 and reduces Histone H3 lysine 4 trimethylation (H3K4me3) by interacting with and probably recruiting the H3K27 methyltransferase polycomb repressive complex 2 (PRC2) and H3K4 demethylase KDM5B to chromatin. Our findings identify an METTL3-independent role of METTL14 in maintaining the integrity of bivalent domains in mESCs, thus indicating a mechanism of bivalent domain regulation in mammals." . 37314930 . M6ACROT03057 REG00006 . Histone modification / Methylation EPIREG00037 EPITAR00205 . . m6A Direct Enhancement Histone modification m6A modification directly impacts histone modification through recruiting histone-associated enzymes "METTL14, but not METTL3, binds Histone H3 lysine 27 trimethylation (H3K27me3) and recruits KDM6B to induce H3K27me3 demethylation independent of METTL3." . 37030005 . M6ACROT03058 REG00007 M6ATAR01488 Histone modification / Lactylation EPIREG00035 EPITAR00208 EPITAR00027 Down regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "Lactate regulates N6-methyladenosine (m6A) modification levels by facilitating p300/CBP-mediated Histone H3 lysine 18 lactylation (H3K18la) binding to the METTL3 promoter site. The METTL3-mediated m6A modification is enriched in Long-chain-fatty-acid--CoA ligase 4 (ACSL4), and its mRNA stability is regulated through a YTHDC1-dependent pathway." M6ADIS0180 38852200 . M6ACROT03059 REG00007 M6ATAR01488 Histone modification / Lactylation EPIREG00034 EPITAR00208 EPITAR00027 Down regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "Lactate regulates N6-methyladenosine (m6A) modification levels by facilitating p300/CREBBP-mediated Histone H3 lysine 18 lactylation (H3K18la) binding to the METTL3 promoter site. The METTL3-mediated m6A modification is enriched in Long-chain-fatty-acid--CoA ligase 4 (ACSL4), and its mRNA stability is regulated through a YTHDC1-dependent pathway." M6ADIS0180 38852200 . M6ACROT03060 REG00022 M6ATAR01488 Histone modification / Lactylation EPIREG00035 EPITAR00208 EPITAR00027 Down regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "Lactate regulates N6-methyladenosine (m6A) modification levels by facilitating p300/CBP-mediated Histone H3 lysine 18 lactylation (H3K18la) binding to the METTL3 promoter site. The METTL3-mediated m6A modification is enriched in Long-chain-fatty-acid--CoA ligase 4 (ACSL4), and its mRNA stability is regulated through a YTHDC1-dependent pathway." M6ADIS0180 38852200 . M6ACROT03061 REG00022 M6ATAR01488 Histone modification / Lactylation EPIREG00034 EPITAR00208 EPITAR00027 Down regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "Lactate regulates N6-methyladenosine (m6A) modification levels by facilitating p300/CREBBP-mediated Histone H3 lysine 18 lactylation (H3K18la) binding to the METTL3 promoter site. The METTL3-mediated m6A modification is enriched in Long-chain-fatty-acid--CoA ligase 4 (ACSL4), and its mRNA stability is regulated through a YTHDC1-dependent pathway." M6ADIS0180 38852200 . M6ACROT03062 REG00022 M6ATAR00150 Histone modification / Methylation EPIREG00036 EPITAR00205 EPITAR00467 . Histone modification Direct Inhibition m6A histone modification regulates m6A modification through both regulatory proteins targeting the same gene "Low expression of Maternally expressed 3 (MEG3) is caused by EZH2-mediated Histone H3 lysine 27 trimethylation (H3K27me3) modification of the MEG3 gene locus, and this is associated with the poor prognosis of OSCC. MEG3 was modified by m6A and bound to YTHDC1." M6ADIS0055 36468944 . M6ACROT03063 REG00006 M6ATAR01603 Histone modification / Methylation EPIREG00054 EPITAR00210 EPITAR00554 Up regulation m6A Indirect Enhancement Histone modification m6A modification indirectly regulates histone modification through downstream signaling pathways "METTL14-mediated upregulation of HOX transcript antisense RNA (HOTAIR) resulted in the repression of PPP1CA, which in turn facilitated the recruitment of KDM1A, thus catalyzing Histone H3 lysine 4 monomethylation (H3K4me1) demethylation and promoting oxycodone addiction." M6ADIS0398 39046182 M6ADRUG0212 M6ACROT03064 REG00006 M6ATAR01604 Histone modification / Methylation EPIREG00053 EPITAR00204 EPITAR00195 Up regulation Histone modification Direct Inhibition m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "KDM5B downregulated METTL14 expression at the transcriptional level in a Histone H3 lysine 4 trimethylation (H3K4me3)-dependent manner, while METTL14 modulated Long intergenic non-protein coding RNA 2747 (LINC02747) expression via m6A modification. Our results demonstrate a synergy of multiple mechanisms in regulating the malignant phenotype of NSCLC, revealing the complex regulation involved in the occurrence and development of cancer." M6ADIS0007 38888105 . M6ACROT03065 REG00009 M6ATAR00627 Histone modification / Acetylation EPIREG00034 EPITAR00203 EPITAR00269 Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator WTAP upregulated in NPC was fine-tuned by CREBBP-mediated Histone H3 lysine 27 acetylation (H3K27ac). WTAP-mediated m6A modification of lncRNA DIAPH1 antisense RNA 1 (DIAPH1-AS1) enhances its stability to facilitate nasopharyngeal carcinoma growth and metastasis M6ADIS0054 34999731 . M6ACROT03066 REG00005 M6ATAR01013 Histone modification / Methylation EPIREG00043 EPITAR00206 EPITAR00555 Up regulation m6A Direct Enhancement Histone modification m6A modification directly impacts histone modification through recruiting histone-associated enzymes ALKBH5-demethylated lncRNA small nucleolar RNA host gene 15 (SNHG15) promotes myeloma tumorigenicity by increasing chromatin accessibility and recruiting Histone H3 lysine 36 trimethylation (H3K36me3) modifier SETD2 to activate H3K36me3-associated downstream transcription such as CDH4. M6ADIS0048 38145297 . M6ACROT03067 REG00022 M6ATAR00979 Histone modification / Methylation EPIREG00032 EPITAR00202 EPITAR00468 . m6A Direct Enhancement Histone modification m6A modification directly impacts histone modification through recruiting histone-associated enzymes "m6A-modified FAM111A divergent transcript (FAM111A-DT) bound to FAM111A promoter and also interacted with m6A reader YTHDC1, which further bound and recruited histone demethylase KDM3B to FAM111A promoter, leading to the reduction of the repressive histone mark Histone H3 lysine 9 dimethylation (H3K9me2) and transcriptional activation of FAM111A." M6ADIS0006 37400994 . M6ACROT03068 REG00001 M6ATAR00098 Histone modification / Acetylation EPIREG00034 EPITAR00203 EPITAR00556 Up regulation m6A Indirect Enhancement Histone modification m6A modification indirectly regulates histone modification through downstream signaling pathways "HOXC13 antisense RNA (HOXC13-AS) augmented FZD through cAMP-response element binding protein-binding protein (CREBBP)-modulated histone H3 on lysine 27 acetylation (Histone H3 lysine 27 acetylation (H3K27ac)). Additionally, FTO-stabilized HOXC13-AS epigenetically up-regulated FZD6 and activated Wnt/beta-catenin signaling to drive CC proliferation, invasion, and EMT, suggesting HOXC13-AS as a potential target for CC treatment." M6ADIS0008 34564982 . M6ACROT03069 REG00017 M6ATAR01069 Histone modification / Acetylation EPIREG00035 EPITAR00203 EPITAR00186 Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator METTL16 regulated PR domain zinc finger protein 15 (PRDM15) protein expression via YTHDF1-dependent translation.the histone acetyltransferase p300 cooperated with the transcription factor YY1 to regulate METTL16 gene expression via Histone H3 lysine 27 acetylation (H3K27ac) in CCA cells. M6ADIS0006 37817227 . M6ACROT03070 REG00024 M6ATAR01069 Histone modification / Acetylation EPIREG00035 EPITAR00203 EPITAR00186 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways METTL16 regulated PR domain zinc finger protein 15 (PRDM15) protein expression via YTHDF1-dependent translation.the histone acetyltransferase p300 cooperated with the transcription factor YY1 to regulate METTL16 gene expression via Histone H3 lysine 27 acetylation (H3K27ac) in CCA cells. M6ADIS0006 37817227 . M6ACROT03071 REG00007 M6ATAR00717 Histone modification / Methylation EPIREG00039 EPITAR00204 EPITAR00027 . Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator KMT2A induced rapid Histone H3 lysine 4 trimethylation (H3K4me3) of the promoter of the methyltransferase-like 3 gene (METTL3) and resulted in its overexpression. METTL3 overexpression evokes N6-methyladenosine (m6A)-dependent miR-503 biogenesis in endothelial cells. M6ADIS0159 35452193 M6ADRUG0213 M6ACROT03072 REG00007 M6ATAR00401 Histone modification / Methylation EPIREG00042 EPITAR00211 EPITAR00109 Down regulation Histone modification Indirect Inhibition m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "JMJD1C increased MIR302A expression through promoting Histone H3 lysine 9 monomethylation (H3K9me1) demethylation at the miR-302a promoter region. miR-302a was identified to target METTL3, which could inhibit Suppressor of cytokine signaling 2 (SOCS2) expression via m6A modification." M6ADIS0001 34586733 . M6ACROT03073 REG00008 M6ATAR00336 Histone modification / Methylation EPIREG00055 EPITAR00204 EPITAR00470 Down regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "KDM5A, as a Histone H3 lysine 4 trimethylation (H3K4me3) demethylase, bound to the hsa-miR-495 promoter, which led to inhibition of its transcription and expression. As a target of miR-495, YTHDF2 could inhibit MOB kinase activator 3B (MOB3B) expression by recognizing m6A modification of MOB3B mRNA and inducing mRNA degradation." M6ADIS0068 33087165 . M6ACROT03074 REG00004 M6ATAR01471 Histone modification / Methylation EPIREG00056 EPITAR00212 . Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through recruiting m6A regulator "the arginine demethylase JMJD6 promotes the demethylation of HNRNPA2B1 at Arg226 and activates its translocation to cytoplasm, which further magnifies the expression of Cyclic GMP-AMP synthase (CGAS), IFI16, and STING" . 31320558 . M6ACROT03075 REG00004 M6ATAR01606 Histone modification / Methylation EPIREG00056 EPITAR00212 . Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through recruiting m6A regulator "the arginine demethylase JMJD6 promotes the demethylation of HNRNPA2B1 at Arg226 and activates its translocation to cytoplasm, which further magnifies the expression of CGAS, Gamma-interferon-inducible protein 16 (IFI16), and STING" . 31320558 . M6ACROT03076 REG00004 M6ATAR00419 Histone modification / Methylation EPIREG00056 EPITAR00212 . Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through recruiting m6A regulator "the arginine demethylase JMJD6 promotes the demethylation of HNRNPA2B1 at Arg226 and activates its translocation to cytoplasm, which further magnifies the expression of CGAS, IFI16, and Stimulator of interferon genes protein (STING1)" . 31320558 . M6ACROT03077 REG00007 M6ATAR01408 Histone modification / Propionylation . EPITAR00213 EPITAR00543 Up regulation m6A Indirect Enhancement Histone modification m6A modification indirectly regulates histone modification through downstream signaling pathways "RPN11 deubiquitinates and stabilizes METTL3 to enhance the m6A modification and expression of acyl-coenzyme A (CoA) synthetase short-chain family member 3 (Acyl-CoA synthetase short-chain family member 3, mitochondrial (ACSS3)), which generates propionyl-CoA to upregulate lipid metabolism genes (ACACB, Fasn, Me1, Mid1ip1) via Histone H3 lysine 14 propionylation (H3K14pr). The RPN11-METTL3-ACSS3-histone propionylation pathway is activated in the livers of patients with NAFLD." M6ADIS0107 39146936 . M6ACROT03078 REG00007 M6ATAR01408 Histone modification / Propionylation . EPITAR00214 EPITAR00543 Up regulation m6A Indirect Enhancement Histone modification m6A modification indirectly regulates histone modification through downstream signaling pathways "RPN11 deubiquitinates and stabilizes METTL3 to enhance the m6A modification and expression of acyl-coenzyme A (CoA) synthetase short-chain family member 3 (Acyl-CoA synthetase short-chain family member 3, mitochondrial (ACSS3)), which generates propionyl-CoA to upregulate lipid metabolism genes (ACACB, Fasn, Me1, Mid1ip1) via Histone H3 lysine 23 propionylation (H3k23pr). The RPN11-METTL3-ACSS3-histone propionylation pathway is activated in the livers of patients with NAFLD." M6ADIS0107 39146936 . M6ACROT03079 REG00013 M6ATAR01608 Histone modification / Lactylation . EPITAR00208 . Up regulation m6A Indirect Enhancement Histone modification m6A modification indirectly regulates histone modification through downstream signaling pathways "IGF2BP2 mediates Histone H3 lysine 18 lactylation (H3K18la) and regulates the expression of Fructose-bisphosphate aldolase A (ALDOA), a key target in the glycolytic metabolic pathway, which in turn regulates HSCs activation. " M6ADIS0017 38443347 . M6ACROT03080 REG00013 M6ATAR00510 Histone modification / Acetylation EPIREG00035 EPITAR00203 EPITAR00557 Up regulation m6A Indirect Enhancement Histone modification m6A modification indirectly regulates histone modification through downstream signaling pathways The promoter of PACERR was a target of Krueppel-like factor 12 (KLF12) and LncRNA-PACERR recruited p300 to increase Histone H3 lysine 27 acetylation (H3K27ac) by interacting with KLF12 in nucleus. The expression of LncRNA-PACERR is activated by EP300-mediated H3K27ac. LncRNA-PACERR induces pro-tumour macrophages via interacting with miR-671-3p and m6A-reader IGF2BP2 in pancreatic ductal adenocarcinoma M6ADIS0061 35526050 . M6ACROT03081 REG00005 M6ATAR00249 Histone modification / Methylation EPIREG00036 EPITAR00205 . Up regulation m6A Direct Enhancement Histone modification m6A modification impacts directly histone modification through modulating the expression level of histone-associated enzymes "Increased Histone-lysine N-methyltransferase EZH2 (EZH2) expression was due to the increased expression of m6A demethylase ALKBH5 and decreased expression of the m6A reader protein YTHDF2. YTHDF2 directly bind to the m6A modification site of EZH2 to promote EZH2 mRNA degradation in ESCs. Enhancer of zeste homology 2 (EZH2) is a methyltransferase which catalyses Histone H3 lysine 27 trimethylation (H3K27me3), leading to decreased expression levels of target genes." M6ADIS0144 38344897 . M6ACROT03082 REG00008 M6ATAR00249 Histone modification / Methylation EPIREG00036 EPITAR00205 . Down regulation m6A Direct Inhibition Histone modification m6A modification impacts directly histone modification through modulating the expression level of histone-associated enzymes "Increased Histone-lysine N-methyltransferase EZH2 (EZH2) expression was due to the increased expression of m6A demethylase ALKBH5 and decreased expression of the m6A reader protein YTHDF2. YTHDF2 directly bind to the m6A modification site of EZH2 to promote EZH2 mRNA degradation in ESCs. Enhancer of zeste homology 2 (EZH2) is a methyltransferase which catalyses Histone H3 lysine 27 trimethylation (H3K27me3), leading to decreased expression levels of target genes." M6ADIS0144 38344897 . M6ACROT03083 REG00008 M6ATAR00768 Histone modification / Acetylation EPIREG00057 EPITAR00148 . Up regulation m6A Direct Enhancement Histone modification m6A modification impacts directly histone modification through modulating the expression level of histone-associated enzymes "m6A methylation recognized by m6A reader-YTHDF2 enhanced the stability of Histone deacetylase 4 (HDAC4), and then promoted glycolytic metabolism and migration of PC cells. m6A methylation regulates hypoxia-induced pancreatic cancer glycolytic metabolism through ALKBH5-HDAC4-Hypoxia-inducible factor 1-alpha (HIF-1-Alpha/HIF1A) positive feedback loop" M6ADIS0061 37149664 . M6ACROT03084 REG00005 M6ATAR00768 Histone modification / Acetylation EPIREG00057 EPITAR00148 . Down regulation m6A Direct Inhibition Histone modification m6A modification impacts directly histone modification through modulating the expression level of histone-associated enzymes "m6A methylation recognized by m6A reader-YTHDF2 enhanced the stability of Histone deacetylase 4 (HDAC4), and then promoted glycolytic metabolism and migration of PC cells. m6A methylation regulates hypoxia-induced pancreatic cancer glycolytic metabolism through ALKBH5-HDAC4-Hypoxia-inducible factor 1-alpha (HIF-1-Alpha/HIF1A) positive feedback loop" M6ADIS0061 37149664 . M6ACROT03085 REG00008 M6ATAR01609 Histone modification / Lactylation EPIREG00035 EPITAR00208 EPITAR00232 Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator The m6A methyltransferase METTL3 modifies Potassium channel subfamily K member 6 (KCNK6) promoting on inflammation associated carcinogenesis is essential for colon homeostasis and defense system through histone lactylation dependent YTHDF2 binding. Histone lactylation activates the transcription of YTHDF2 through p300-mediated Histone H3 lysine 18 lactylation (H3K18la) modification. M6ADIS0059 39269733 . M6ACROT03086 REG00001 M6ATAR00210 Histone modification / Lactylation EPIREG00035 EPITAR00208 EPITAR00179 Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "FTO affected EC features via modulating Cyclin-dependent kinase 2 (CDK2) mRNA stability in an m6A-YTHDF2-dependent manner. FTO up-regulation under diabetic conditions was driven by p300-mediated Histone H3 lysine 18 lactylation (H3K18la). FB23-2, an inhibitor to FTO's m6A demethylase activity, suppressed angiogenic phenotypes in vitro." M6ADIS0015 40281307 M6ADRUG0152 M6ACROT03087 REG00008 M6ATAR00210 Histone modification / Lactylation EPIREG00035 EPITAR00208 EPITAR00179 Down regulation Histone modification Indirect Inhibition m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "FTO affected EC features via modulating Cyclin-dependent kinase 2 (CDK2) mRNA stability in an m6A-YTHDF2-dependent manner. FTO up-regulation under diabetic conditions was driven by p300-mediated Histone H3 lysine 18 lactylation (H3K18la). FB23-2, an inhibitor to FTO's m6A demethylase activity, suppressed angiogenic phenotypes in vitro." M6ADIS0015 40281307 M6ADRUG0152 M6ACROT03088 REG00005 M6ATAR01610 Histone modification / Acetylation EPIREG00058 EPITAR00203 EPITAR00547 Down regulation m6A Direct Inhibition Histone modification m6A modification impacts directly histone modification through modulating the expression level of histone-associated enzymes "ALKBH5 was found to reduce m6A methylation levels on Histone acetyltransferase KAT2A (KAT2A) mRNA, leading to its upregulation. YTHDF2 played a crucial role as an m6A reader protein mediating the degradation of Kat2a mRNA. Furthermore, Kat2a promoted ferroptosis by increasing TFRC and Hmox1 expression via enhancing the enrichment of Histone H3 lysine 27 acetylation (H3K27ac) and H3K9ac on their promoter regions. In conclusion, our findings unveil a novel role for the Kat2a-ferroptosis axis in DCM pathogenesis, providing valuable insights for potential clinical interventions." M6ADIS0142 38858351 . M6ACROT03089 REG00008 M6ATAR01610 Histone modification / Acetylation EPIREG00058 EPITAR00203 EPITAR00547 Up regulation m6A Direct Enhancement Histone modification m6A modification impacts directly histone modification through modulating the expression level of histone-associated enzymes "ALKBH5 was found to reduce m6A methylation levels on Histone acetyltransferase KAT2A (KAT2A) mRNA, leading to its upregulation. YTHDF2 played a crucial role as an m6A reader protein mediating the degradation of Kat2a mRNA. Furthermore, Kat2a promoted ferroptosis by increasing TFRC and Hmox1 expression via enhancing the enrichment of Histone H3 lysine 27 acetylation (H3K27ac) and H3K9ac on their promoter regions. In conclusion, our findings unveil a novel role for the Kat2a-ferroptosis axis in DCM pathogenesis, providing valuable insights for potential clinical interventions." M6ADIS0142 38858351 . M6ACROT03090 REG00005 M6ATAR01610 Histone modification / Acetylation EPIREG00058 EPITAR00209 EPITAR00547 Down regulation m6A Direct Inhibition Histone modification m6A modification impacts directly histone modification through modulating the expression level of histone-associated enzymes "ALKBH5 was found to reduce m6A methylation levels on Histone acetyltransferase KAT2A (KAT2A) mRNA, leading to its upregulation. YTHDF2 played a crucial role as an m6A reader protein mediating the degradation of Kat2a mRNA. Furthermore, Kat2a promoted ferroptosis by increasing TFRC and Hmox1 expression via enhancing the enrichment of H3K27ac and Histone H3 lysine 9 acetylation (H3K9ac) on their promoter regions. In conclusion, our findings unveil a novel role for the Kat2a-ferroptosis axis in DCM pathogenesis, providing valuable insights for potential clinical interventions." M6ADIS0142 38858351 . M6ACROT03091 REG00008 M6ATAR01610 Histone modification / Acetylation EPIREG00058 EPITAR00209 EPITAR00547 Up regulation m6A Direct Enhancement Histone modification m6A modification impacts directly histone modification through modulating the expression level of histone-associated enzymes "ALKBH5 was found to reduce m6A methylation levels on Histone acetyltransferase KAT2A (KAT2A) mRNA, leading to its upregulation. YTHDF2 played a crucial role as an m6A reader protein mediating the degradation of Kat2a mRNA. Furthermore, Kat2a promoted ferroptosis by increasing TFRC and Hmox1 expression via enhancing the enrichment of H3K27ac and Histone H3 lysine 9 acetylation (H3K9ac) on their promoter regions. In conclusion, our findings unveil a novel role for the Kat2a-ferroptosis axis in DCM pathogenesis, providing valuable insights for potential clinical interventions." M6ADIS0142 38858351 . M6ACROT03092 REG00005 M6ATAR01611 Histone modification / Ubiquitination EPIREG00059 EPITAR00216 EPITAR00283 Down regulation m6A Direct Inhibition Histone modification m6A modification impacts directly histone modification through modulating the expression level of histone-associated enzymes "Putative E3 ubiquitin-protein ligase UBR7 (UBR7) regulates Histone H2B lysine 120 ubiquitination (H2BK120ub) to bind to KEAP1 promoter through H2BK120ub monoubiquitination, thereby modulating Keap1 expression and downstream Nrf2/Bach1/HK2 signaling. Pharmaceutical and genetic inhibition of glycolytic enzymes attenuate the promoting effect of UBR7 deficiency on tumor growth. In addition, methyltransferase ALKBH5, downregulated in HCC, regulated UBR7 expression in an m6A-dependent manner." M6ADIS0006 36419136 . M6ACROT03093 REG00022 M6ATAR01612 Histone modification / Methylation EPIREG00031 EPITAR00201 . Up regulation m6A Indirect Inhibition Histone modification m6A modification indirectly regulates histone modification through downstream signaling pathways "YTHDC1 binds to the transcripts of retrotransposons (such as intracisternal A particles, Endogenous Retrovirus-K (ERVK) and LINE1) in mouse ES cells and its depletion results in the reactivation of these silenced retrotransposons, accompanied by a global decrease in SETDB1-mediated Histone H3 lysine 9 trimethylation (H3K9me3)." . 33658714 . M6ACROT03094 REG00022 M6ATAR01613 Histone modification / Methylation EPIREG00031 EPITAR00201 . Up regulation m6A Indirect Inhibition Histone modification m6A modification indirectly regulates histone modification through downstream signaling pathways "YTHDC1 binds to the transcripts of retrotransposons (such as intracisternal A particles, ERVK and LINE-1 retrotransposable element ORF1 protein (LINE1)) in mouse ES cells and its depletion results in the reactivation of these silenced retrotransposons, accompanied by a global decrease in SETDB1-mediated Histone H3 lysine 9 trimethylation (H3K9me3)." . 33658714 . M6ACROT03095 REG00009 M6ATAR00605 Histone modification / Acetylation EPIREG00035 EPITAR00203 EPITAR00269 Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "Histone acetyltransferase p300 promotes WTAP transcription through Histone H3 lysine 27 acetylation (H3K27ac). WTAP-mediated N6-methyladenosine modification of NACHT, LRR and PYD domains-containing protein 3 (NLRP3) mRNA in kidney injury of diabetic nephropathy. WTAP expression in HK-2 cells was examined with the introduction of C646, a histone acetyltransferase p300 inhibitor." M6ADIS0117 35761192 M6ADRUG0214 M6ACROT03096 REG00007 M6ATAR01614 Histone modification / Methylation EPIREG00060 EPITAR00201 . . m6A Direct Inhibition Histone modification m6A modification directly impacts histone modification through recruiting histone-associated enzymes "SUV39H1/H2 protein, the methyltransferases catalyzing Histone H3 lysine 9 trimethylation (H3K9me3) were dramatically elevated in METTL3/METTL14 deficient cells, which causes an accumulation and infiltration of H3K9me3 across the whole nucleolus and impairs the LLPS. Mechanistically, METTL3/METTL14 complex serves as an essential adapter for CRL4 E3 ubiquitin ligase targeting SUV39H1/SUV39H2 for polyubiquitination and proteasomal degradation and therefore prevents H3K9me3 accumulation in nucleoli. " . 39169036 . M6ACROT03097 REG00007 M6ATAR01614 Histone modification / Methylation EPIREG00061 EPITAR00201 . . m6A Direct Inhibition Histone modification m6A modification directly impacts histone modification through recruiting histone-associated enzymes "SUV39H1/H2 protein, the methyltransferases catalyzing Histone H3 lysine 9 trimethylation (H3K9me3) were dramatically elevated in METTL3/METTL14 deficient cells, which causes an accumulation and infiltration of H3K9me3 across the whole nucleolus and impairs the LLPS. Mechanistically, METTL3/METTL14 complex serves as an essential adapter for CRL4 E3 ubiquitin ligase targeting SUV39H1/SUV39H2 for polyubiquitination and proteasomal degradation and therefore prevents H3K9me3 accumulation in nucleoli. " . 39169036 . M6ACROT03098 REG00006 M6ATAR01614 Histone modification / Methylation EPIREG00060 EPITAR00201 . . m6A Direct Inhibition Histone modification m6A modification directly impacts histone modification through recruiting histone-associated enzymes "SUV39H1/H2 protein, the methyltransferases catalyzing Histone H3 lysine 9 trimethylation (H3K9me3) were dramatically elevated in METTL3/METTL14 deficient cells, which causes an accumulation and infiltration of H3K9me3 across the whole nucleolus and impairs the LLPS. Mechanistically, METTL3/METTL14 complex serves as an essential adapter for CRL4 E3 ubiquitin ligase targeting SUV39H1/SUV39H2 for polyubiquitination and proteasomal degradation and therefore prevents H3K9me3 accumulation in nucleoli. " . 39169036 . M6ACROT03099 REG00006 M6ATAR01614 Histone modification / Methylation EPIREG00061 EPITAR00201 . . m6A Direct Inhibition Histone modification m6A modification directly impacts histone modification through recruiting histone-associated enzymes "SUV39H1/H2 protein, the methyltransferases catalyzing Histone H3 lysine 9 trimethylation (H3K9me3) were dramatically elevated in METTL3/METTL14 deficient cells, which causes an accumulation and infiltration of H3K9me3 across the whole nucleolus and impairs the LLPS. Mechanistically, METTL3/METTL14 complex serves as an essential adapter for CRL4 E3 ubiquitin ligase targeting SUV39H1/SUV39H2 for polyubiquitination and proteasomal degradation and therefore prevents H3K9me3 accumulation in nucleoli. " . 39169036 . M6ACROT03100 REG00005 M6ATAR01012 Histone modification / Acetylation EPIREG00062 EPITAR00203 EPITAR00183 Down regulation Histone modification Direct Inhibition m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "Mechanically, HDAC2-reduced Histone H3 lysine 27 acetylation (H3K27ac) inhibits ALKBH5 transcription in CRC, whereas ectopic ALKBH5 expression decreases tumorigenesis of CRC cells and protects mice from colitis-associated tumor development.METTL14/ALKBH5/IGF2BPs combine to modulate JmjC domain-containing protein 8 (JMJD8) stability in an m6A-dependent manner, which increases glycolysis and accelerates the development of CRC by enhancing the enzymatic activity of PKM2." M6ADIS0059 37310898 . M6ACROT03101 REG00012 M6ATAR01012 Histone modification / Acetylation EPIREG00062 EPITAR00203 EPITAR00183 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "Mechanically, HDAC2-reduced Histone H3 lysine 27 acetylation (H3K27ac) inhibits ALKBH5 transcription in CRC, whereas ectopic ALKBH5 expression decreases tumorigenesis of CRC cells and protects mice from colitis-associated tumor development.METTL14/ALKBH5/IGF2BP1 combine to modulate JmjC domain-containing protein 8 (JMJD8) stability in an m6A-dependent manner, which increases glycolysis and accelerates the development of CRC by enhancing the enzymatic activity of PKM2." M6ADIS0059 37310898 . M6ACROT03102 REG00013 M6ATAR01012 Histone modification / Acetylation EPIREG00062 EPITAR00203 EPITAR00183 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "Mechanically, HDAC2-reduced Histone H3 lysine 27 acetylation (H3K27ac) inhibits ALKBH5 transcription in CRC, whereas ectopic ALKBH5 expression decreases tumorigenesis of CRC cells and protects mice from colitis-associated tumor development.METTL14/ALKBH5/IGF2BP2 combine to modulate JmjC domain-containing protein 8 (JMJD8) stability in an m6A-dependent manner, which increases glycolysis and accelerates the development of CRC by enhancing the enzymatic activity of PKM2." M6ADIS0059 37310898 . M6ACROT03103 REG00014 M6ATAR01012 Histone modification / Acetylation EPIREG00062 EPITAR00203 EPITAR00183 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "Mechanically, HDAC2-reduced Histone H3 lysine 27 acetylation (H3K27ac) inhibits ALKBH5 transcription in CRC, whereas ectopic ALKBH5 expression decreases tumorigenesis of CRC cells and protects mice from colitis-associated tumor development.METTL14/ALKBH5/IGF2BP3 combine to modulate JmjC domain-containing protein 8 (JMJD8) stability in an m6A-dependent manner, which increases glycolysis and accelerates the development of CRC by enhancing the enzymatic activity of PKM2." M6ADIS0059 37310898 . M6ACROT03104 REG00005 M6ATAR01615 Histone modification / Methylation EPIREG00031 EPITAR00217 . Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "Polo like kinase 3 (PLK3) methylation decreases PLK3 phosphorylation of HIF1alpha and thereby increases HIF1alpha stability. HIF1alpha, in turn, upregulates ALKBH5 to reduce m6A modification of Long intergenic non-protein coding RNA 115 (LINC00115), resulting in attenuated degradation of YTHDF2-dependent m6A-modified RNA and enhanced LINC00115 stability. Thus, this positive feedback loop provokes BCSC phenotypes and enhances chemoresistance and metastasis in triple-negative breast cancer. SETDB1 inhibitor TTD-IN with LINC00115 ASO sensitizes PTX-resistant cell response to chemotherapy in a xenograft animal model. Correlative expression of LINC00115, methylation PLK3, SETDB1, and HIF1alpha are prognostic for clinical triple-negative breast cancers." M6ADIS0184 38520019 M6ADRUG0215 M6ACROT03105 REG00008 M6ATAR01615 Histone modification / Methylation EPIREG00031 EPITAR00217 . Down regulation Histone modification Indirect Inhibition m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "Polo like kinase 3 (PLK3) methylation decreases PLK3 phosphorylation of HIF1alpha and thereby increases HIF1alpha stability. HIF1alpha, in turn, upregulates ALKBH5 to reduce m6A modification of Long intergenic non-protein coding RNA 115 (LINC00115), resulting in attenuated degradation of YTHDF2-dependent m6A-modified RNA and enhanced LINC00115 stability. Thus, this positive feedback loop provokes BCSC phenotypes and enhances chemoresistance and metastasis in triple-negative breast cancer. SETDB1 inhibitor TTD-IN with LINC00115 ASO sensitizes PTX-resistant cell response to chemotherapy in a xenograft animal model. Correlative expression of LINC00115, methylation PLK3, SETDB1, and HIF1alpha are prognostic for clinical triple-negative breast cancers." M6ADIS0184 38520019 M6ADRUG0215 M6ACROT03106 REG00007 M6ATAR00341 Histone modification / Lactylation . EPITAR00208 EPITAR00473 Up regulation Histone modification Indirect Enhancement m6A Histone modification indirectly regulates m6A modification through downstream signaling pathways "AP001885.4 was overexpressed in ESCC cells because of a higher Histone H3 lysine 18 lactylation (H3K18la) level in the promoter and amplification, then enhanced histone lactylation- and NF-kappaB (p65)-dependent transcription activation and METTL3-mediated mRNA stability of c-myc eventually upregulated Myc proto-oncogene protein (MYC) and promoted cell proliferation" M6ADIS0056 39502790 . M6ACROT03107 REG00007 M6ATAR00605 Histone modification / Acetylation . EPITAR00203 EPITAR00474 Down regulation Histone modification Indirect Enhancement m6A Histone modification indirectly regulates m6A modification through downstream signaling pathways "Gain of H3K4me1 and Gain of H3K4me1 and Histone H3 lysine 27 acetylation (H3K27ac) led to the activation of MIR570HG expression. LINC00969 interacts with EZH2 and METTL3, transcriptionally regulates the level of H3K27me3 in the NACHT, LRR and PYD domains-containing protein 3 (NLRP3) promoter region, and posttranscriptionally modifies the m6A level of NLRP3 in an m6A-YTHDF2-dependent manner" M6ADIS0007 37156816 M6ADRUG0030 M6ACROT03108 REG00008 M6ATAR00605 Histone modification / Acetylation . EPITAR00203 EPITAR00474 Down regulation Histone modification Indirect Enhancement m6A Histone modification indirectly regulates m6A modification through downstream signaling pathways "Gain of H3K4me1 and Gain of H3K4me1 and Histone H3 lysine 27 acetylation (H3K27ac) led to the activation of MIR570HG expression. LINC00969 interacts with EZH2 and METTL3, transcriptionally regulates the level of H3K27me3 in the NACHT, LRR and PYD domains-containing protein 3 (NLRP3) promoter region, and posttranscriptionally modifies the m6A level of NLRP3 in an m6A-YTHDF2-dependent manner" M6ADIS0007 37156816 M6ADRUG0030 M6ACROT03109 REG00007 M6ATAR00605 Histone modification / Methylation . EPITAR00210 EPITAR00474 Down regulation Histone modification Indirect Enhancement m6A Histone modification indirectly regulates m6A modification through downstream signaling pathways "Gain of Histone H3 lysine 4 monomethylation (H3K4me1) and Gain of H3K4me1 and H3K27ac led to the activation of MIR570HG expression. LINC00969 interacts with EZH2 and METTL3, transcriptionally regulates the level of H3K27me3 in the NACHT, LRR and PYD domains-containing protein 3 (NLRP3) promoter region, and posttranscriptionally modifies the m6A level of NLRP3 in an m6A-YTHDF2-dependent manner" M6ADIS0007 37156816 M6ADRUG0030 M6ACROT03110 REG00008 M6ATAR00605 Histone modification / Methylation . EPITAR00210 EPITAR00474 Down regulation Histone modification Indirect Enhancement m6A Histone modification indirectly regulates m6A modification through downstream signaling pathways "Gain of Histone H3 lysine 4 monomethylation (H3K4me1) and Gain of H3K4me1 and H3K27ac led to the activation of MIR570HG expression. LINC00969 interacts with EZH2 and METTL3, transcriptionally regulates the level of H3K27me3 in the NACHT, LRR and PYD domains-containing protein 3 (NLRP3) promoter region, and posttranscriptionally modifies the m6A level of NLRP3 in an m6A-YTHDF2-dependent manner" M6ADIS0007 37156816 M6ADRUG0030 M6ACROT03111 REG00007 M6ATAR01616 Histone modification / Methylation EPIREG00063 EPITAR00218 EPITAR00475 Up regulation m6A Direct Enhancement Histone modification m6A modification impacts directly histone modification through modulating the expression level of histone-associated enzymes "Mechanistically, Histone-lysine N-methyltransferase SETMAR (SETMAR) methylates Histone H3 lysine 36 dimethylation (H3K36me2) in the SMARCA2 promoter region to promote SMARCA2 transcription. SMARCA2 can increase H3K27Ac enrichment and bind to enhancers of the thyroid differentiation transcription factors (PAX8 and FOXE1) to promote their expression by enhancing chromatin accessibility. Moreover, METTL3-mediated m6A methylation of SETAMR mRNA is observed and showed that this medication can affect SETMAR expression in an IGF2BP3-dependent manner. " M6ADIS0073 38900084 . M6ACROT03112 REG00014 M6ATAR01616 Histone modification / Methylation EPIREG00063 EPITAR00218 EPITAR00475 Up regulation m6A Direct Enhancement Histone modification m6A modification impacts directly histone modification through modulating the expression level of histone-associated enzymes "Mechanistically, Histone-lysine N-methyltransferase SETMAR (SETMAR) methylates Histone H3 lysine 36 dimethylation (H3K36me2) in the SMARCA2 promoter region to promote SMARCA2 transcription. SMARCA2 can increase H3K27Ac enrichment and bind to enhancers of the thyroid differentiation transcription factors (PAX8 and FOXE1) to promote their expression by enhancing chromatin accessibility. Moreover, METTL3-mediated m6A methylation of SETAMR mRNA is observed and showed that this medication can affect SETMAR expression in an IGF2BP3-dependent manner. " M6ADIS0073 38900084 . M6ACROT03113 REG00007 M6ATAR01616 Histone modification / Acetylation EPIREG00064 EPITAR00203 EPITAR00549 Up regulation m6A Indirect Enhancement Histone modification m6A modification indirectly regulates histone modification through downstream signaling pathways "Mechanistically, Histone-lysine N-methyltransferase SETMAR (SETMAR) methylates H3K36me2 in the SMARCA2 promoter region to promote SMARCA2 transcription. SMARCA2 can increase Histone H3 lysine 27 acetylation (H3K27ac) enrichment and bind to enhancers of the thyroid differentiation transcription factors (PAX8 and FOXE1) to promote their expression by enhancing chromatin accessibility. Moreover, METTL3-mediated m6A methylation of SETAMR mRNA is observed and showed that this medication can affect SETMAR expression in an IGF2BP3-dependent manner. " M6ADIS0073 38900084 . M6ACROT03114 REG00014 M6ATAR01616 Histone modification / Acetylation EPIREG00064 EPITAR00203 EPITAR00549 Up regulation m6A Indirect Enhancement Histone modification m6A modification indirectly regulates histone modification through downstream signaling pathways "Mechanistically, Histone-lysine N-methyltransferase SETMAR (SETMAR) methylates H3K36me2 in the SMARCA2 promoter region to promote SMARCA2 transcription. SMARCA2 can increase Histone H3 lysine 27 acetylation (H3K27ac) enrichment and bind to enhancers of the thyroid differentiation transcription factors (PAX8 and FOXE1) to promote their expression by enhancing chromatin accessibility. Moreover, METTL3-mediated m6A methylation of SETAMR mRNA is observed and showed that this medication can affect SETMAR expression in an IGF2BP3-dependent manner. " M6ADIS0073 38900084 . M6ACROT03115 REG00014 M6ATAR00800 Histone modification / Acetylation EPIREG00062 EPITAR00219 . Up regulation m6A Indirect Enhancement Histone modification m6A modification indirectly regulates histone modification through downstream signaling pathways "SUMO specific peptidase 1 (SENP1) can desumoylate HDAC2, which enhances Epidermal growth factor receptor (EGFR) transcription and activates the AKT pathway. In addition, we found that IGF2BP3 expression was upregulated in high-risk AML patients and was positively correlated with SENP1 expression. MERIP-qPCR and RIP-qPCR showed that IGF2BP3 binds SENP1 3-UTR in an m6A manner, enhances SENP1 expression, and promotes AKT pathway conduction." M6ADIS0046 38822351 . M6ACROT03116 REG00006 M6ATAR00141 Histone modification / Methylation EPIREG00065 . . Up regulation m6A Indirect Enhancement Histone modification m6A modification indirectly regulates histone modification through downstream signaling pathways "Overall, our findings verified the therapeutic role of silencing METTL14 in OSCC treatment through the Metastasis associated lung adenocarcinoma transcript 1 (MALAT1)/miR-224-5p/KDM2A axis" M6ADIS0055 35467063 . M6ACROT03117 REG00005 M6ATAR00892 Histone modification / Methylation EPIREG00035 EPITAR00203 EPITAR00183 Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "E7 increased ALKBH5 expression through E2F1-mediated activation of the H3K27ac and Histone H3 lysine 4 trimethylation (H3K4me3) histone modifications, as well as post-translational modification mediated by DDX3. ALKBH5-mediated m6A demethylation enhanced the expression of Serine/threonine-protein kinase PAK 6 (PAK5). The m6A reader YTHDF2 bound to PAK5 mRNA and regulated its stability in an m6A-dependent manner. Our data provide evidence that E2F1 promotes ALKBH5 transcription by the p300-mediated H3K27ac and WDR5-mediated H3K4me3 mechanisms." M6ADIS0008 37480971 . M6ACROT03118 REG00008 M6ATAR00892 Histone modification / Methylation EPIREG00035 EPITAR00203 EPITAR00183 Down regulation Histone modification Indirect Inhibition m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "E7 increased ALKBH5 expression through E2F1-mediated activation of the H3K27ac and Histone H3 lysine 4 trimethylation (H3K4me3) histone modifications, as well as post-translational modification mediated by DDX3. ALKBH5-mediated m6A demethylation enhanced the expression of Serine/threonine-protein kinase PAK 6 (PAK5). The m6A reader YTHDF2 bound to PAK5 mRNA and regulated its stability in an m6A-dependent manner. Our data provide evidence that E2F1 promotes ALKBH5 transcription by the p300-mediated H3K27ac and WDR5-mediated H3K4me3 mechanisms." M6ADIS0008 37480971 . M6ACROT03119 REG00005 M6ATAR00892 Histone modification / Acetylation EPIREG00066 EPITAR00204 EPITAR00183 Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "E7 increased ALKBH5 expression through E2F1-mediated activation of the Histone H3 lysine 27 acetylation (H3K27ac) and H3K4me3 histone modifications, as well as post-translational modification mediated by DDX3. ALKBH5-mediated m6A demethylation enhanced the expression of Serine/threonine-protein kinase PAK 6 (PAK5). The m6A reader YTHDF2 bound to PAK5 mRNA and regulated its stability in an m6A-dependent manner. Our data provide evidence that E2F1 promotes ALKBH5 transcription by the p300-mediated H3K27ac and WDR5-mediated H3K4me3 mechanisms." M6ADIS0008 37480971 . M6ACROT03120 REG00008 M6ATAR00892 Histone modification / Acetylation EPIREG00066 EPITAR00204 EPITAR00183 Down regulation Histone modification Indirect Inhibition m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "E7 increased ALKBH5 expression through E2F1-mediated activation of the Histone H3 lysine 27 acetylation (H3K27ac) and H3K4me3 histone modifications, as well as post-translational modification mediated by DDX3. ALKBH5-mediated m6A demethylation enhanced the expression of Serine/threonine-protein kinase PAK 6 (PAK5). The m6A reader YTHDF2 bound to PAK5 mRNA and regulated its stability in an m6A-dependent manner. Our data provide evidence that E2F1 promotes ALKBH5 transcription by the p300-mediated H3K27ac and WDR5-mediated H3K4me3 mechanisms." M6ADIS0008 37480971 . M6ACROT03121 REG00022 M6ATAR01617 Histone modification / Acetylation EPIREG00062 . . Down regulation Histone modification Indirect Inhibition m6A Histone modification indirectly regulates m6A modification through downstream signaling pathways We identified a novel YY1/HDAC2/YTHDC1/Annexin A1 (ANXA1) axis modulating the progression and chemosensitivity of ccRCC. M6ADIS0343 35974388 M6ADRUG0093 M6ACROT03122 REG00008 M6ATAR01618 Histone modification / Methylation . EPITAR00204 EPITAR00232 Up regulation Histone modification Direct Enhancement m6A Histone modification directly impacts m6A modification through modulating the level of m6A regulator "Histone H3 lysine 4 trimethylation (H3K4me3) and H3K27ac modification in the promoter region of YTHDF2 enhanced its expression in HCC, and upregulated YTHDF2 in HCC predicted a worse prognosis. YTHDF2 recognized the m6A modification in the 5'-untranslational region of ETS translocation variant 5 (ETV5) mRNA and recruited eukaryotic translation initiation factor 3 subunit B to facilitate its translation." M6ADIS0006 38247171 . M6ACROT03123 REG00008 M6ATAR01618 Histone modification / Acetylation . EPITAR00203 EPITAR00232 Up regulation Histone modification Direct Enhancement m6A Histone modification directly impacts m6A modification through modulating the level of m6A regulator "H3K4me3 and Histone H3 lysine 27 acetylation (H3K27ac) modification in the promoter region of YTHDF2 enhanced its expression in HCC, and upregulated YTHDF2 in HCC predicted a worse prognosis. YTHDF2 recognized the m6A modification in the 5'-untranslational region of ETS translocation variant 5 (ETV5) mRNA and recruited eukaryotic translation initiation factor 3 subunit B to facilitate its translation." M6ADIS0006 38247171 . M6ACROT03124 REG00001 M6ATAR01486 Histone modification / Acetylation EPIREG00067 EPITAR00203 EPITAR00179 Down regulation Histone modification Direct Inhibition m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "HDACi reduces Ferroptosis suppressor protein 1 (AIFM2) by promoting its mRNA degradation. Specifically, it is confirmed that HDACi specifically targets HDAC1 and promotes the Histone H3 lysine 27 acetylation (H3K27ac) modification of fat mass- and obesity-associated gene (FTO) and AlkB Homolog 5, RNA Demethylase (ALKBH5), which results in significant activation of FTO and ALKBH5. The activation of FTO and ALKBH5 reduces N6-methyladenosine (m6A) modification on FSP1 mRNA, leading to its degradation in an IGF2BP1-dependent manner. Crucially, lactylation of HDAC1 K412 is essential for ferroptosis regulation. Both Vorinostat (SAHA) and Trichostatin A (TSA) notably diminish HDAC1 K412 lactylation in comparison to other HDAC1 inhibitors, exhibiting a consistent trend of increasing susceptibility to ferroptosis. " M6ADIS0059 39888307 M6ADRUG0261 M6ACROT03125 REG00005 M6ATAR01486 Histone modification / Acetylation EPIREG00067 EPITAR00203 EPITAR00183 Down regulation Histone modification Direct Inhibition m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "HDACi reduces Ferroptosis suppressor protein 1 (AIFM2) by promoting its mRNA degradation. Specifically, it is confirmed that HDACi specifically targets HDAC1 and promotes the Histone H3 lysine 27 acetylation (H3K27ac) modification of fat mass- and obesity-associated gene (FTO) and AlkB Homolog 5, RNA Demethylase (ALKBH5), which results in significant activation of FTO and ALKBH5. The activation of FTO and ALKBH5 reduces N6-methyladenosine (m6A) modification on FSP1 mRNA, leading to its degradation in an IGF2BP1-dependent manner. Crucially, lactylation of HDAC1 K412 is essential for ferroptosis regulation. Both Vorinostat (SAHA) and Trichostatin A (TSA) notably diminish HDAC1 K412 lactylation in comparison to other HDAC1 inhibitors, exhibiting a consistent trend of increasing susceptibility to ferroptosis. " M6ADIS0059 39888307 M6ADRUG0261 M6ACROT03126 REG00012 M6ATAR01486 Histone modification / Acetylation EPIREG00067 EPITAR00203 EPITAR00179 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "HDACi reduces Ferroptosis suppressor protein 1 (AIFM2) by promoting its mRNA degradation. Specifically, it is confirmed that HDACi specifically targets HDAC1 and promotes the Histone H3 lysine 27 acetylation (H3K27ac) modification of fat mass- and obesity-associated gene (FTO) and AlkB Homolog 5, RNA Demethylase (ALKBH5), which results in significant activation of FTO and ALKBH5. The activation of FTO and ALKBH5 reduces N6-methyladenosine (m6A) modification on FSP1 mRNA, leading to its degradation in an IGF2BP1-dependent manner. Crucially, lactylation of HDAC1 K412 is essential for ferroptosis regulation. Both Vorinostat (SAHA) and Trichostatin A (TSA) notably diminish HDAC1 K412 lactylation in comparison to other HDAC1 inhibitors, exhibiting a consistent trend of increasing susceptibility to ferroptosis. " M6ADIS0059 39888307 M6ADRUG0261 M6ACROT03127 REG00005 . Histone modification / Acetylation EPIREG00068 EPITAR00183 . . Histone modification Direct Inhibition m6A Histone modification directly impacts m6A modification through recruiting m6A regulator ALKBH5 is acetylated at lysine 235 (K235) by lysine acetyltransferase 8 and deacetylated by HDAC7. The m6A demethylation activity of ALKBH5 is orchestrated by its K235 acetylation and regulatory subunit PSPC1 and that K235 acetylation is necessary for the m6A demethylase activity and oncogenic roles of ALKBH5. . 37369679 . M6ACROT03128 REG00013 M6ATAR01619 Histone modification / Methylation EPIREG00044 EPITAR00204 EPITAR00028 Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator This feeds back upon the IGF2BP2 promoter region by further increasing SETD1A-mediated Histone H3 lysine 4 trimethylation (H3K4me3) level to upregulate IGF2BP2 expression. We demonstrated that this positive feedback loop between IGF2BP2 and Large neutral amino acids transporter small subunit 1 (SLC7A5) promotes lung cancer radioresistance through the AKT/mTOR pathway. M6ADIS0007 38281999 . M6ACROT03129 REG00005 M6ATAR01620 Histone modification / Acetylation EPIREG00069 EPITAR00203 EPITAR00183 Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "HDAC11 downregulation induced by nerve injury increases Histone H3 lysine 27 acetylation (H3K27ac), facilitating the binding of the transcription factor forkhead box protein D3 (FOXD3) to the ALKBH5 promoter and promoting Alkbh5 transcription. The increased ALKBH5 erases m6A sites in 5-hydroxytryptamine receptor 3A (HTR3A) messenger RNA (mRNA), resulting in an inability of YT521-B homology domain 2 (YTHDF2) to bind to Htr3a mRNA, thus causing an increase in 5-HT3A protein expression and 5-HT3 channel currents. " M6ADIS0161 38285939 . M6ACROT03130 REG00008 M6ATAR01620 Histone modification / Acetylation EPIREG00069 EPITAR00203 EPITAR00183 Down regulation Histone modification Indirect Inhibition m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "HDAC11 downregulation induced by nerve injury increases Histone H3 lysine 27 acetylation (H3K27ac), facilitating the binding of the transcription factor forkhead box protein D3 (FOXD3) to the ALKBH5 promoter and promoting Alkbh5 transcription. The increased ALKBH5 erases m6A sites in 5-hydroxytryptamine receptor 3A (HTR3A) messenger RNA (mRNA), resulting in an inability of YT521-B homology domain 2 (YTHDF2) to bind to Htr3a mRNA, thus causing an increase in 5-HT3A protein expression and 5-HT3 channel currents. " M6ADIS0161 38285939 . M6ACROT03131 REG00005 M6ATAR01621 Histone modification / Acetylation EPIREG00035 EPITAR00203 EPITAR00478 Down regulation Histone modification Indirect Enhancement m6A Histone modification indirectly regulates m6A modification through downstream signaling pathways Histone acetylation causes HSPA4 upregulation in GC tumor tissues. HSPA4 upregulation increases the protein stability of m6A demethylase ALKBH5. ALKBH5 decreases Lymphocyte function-associated antigen 3 (CD58) in GC cells through m6A methylation regulation. p300/CREBBP-mediated Histone H3 lysine 27 acetylation (H3K27ac) modification plays an important role in HSPA4 overexpression in GC tissues. M6ADIS0057 38589927 . M6ACROT03132 REG00013 M6ATAR01536 Histone modification / Lactylation EPIREG00035 EPITAR00208 EPITAR00028 Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "CTCF interacts with HNRNPU through a FLG-AS1-dependent mechanism, facilitating the recruitment of p300 and activation of the m6A reader IGF2BP2 by Histone H3 lysine 18 lactylation (H3K18la). This activation promotes histone lactylation at the promoter region of IGF2BP2 stimulating the proliferation of PDAC cells. IGF2BP2 enhanced the mRNA stability of Macrophage colony-stimulating factor 1 (CSF1) and MYC." M6ADIS0061 39616247 . M6ACROT03133 REG00013 M6ATAR00341 Histone modification / Lactylation EPIREG00035 EPITAR00208 EPITAR00028 Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "CTCF interacts with HNRNPU through a FLG-AS1-dependent mechanism, facilitating the recruitment of p300 and activation of the m6A reader IGF2BP2 by Histone H3 lysine 18 lactylation (H3K18la). This activation promotes histone lactylation at the promoter region of IGF2BP2 stimulating the proliferation of PDAC cells. IGF2BP2 enhanced the mRNA stability of CSF1 and Myc proto-oncogene protein (MYC)." M6ADIS0061 39616247 . M6ACROT03134 REG00007 M6ATAR00388 Histone modification / Lactylation EPIREG00051 EPITAR00220 EPITAR00027 Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "LDHA-induced Histone H3 lysine 18 lactylation (H3K18lac) promoted NAFLD progression, where LDHA-induced H3K18lac in METTL3 promoter elevated METTL3 expression, thereby promoting m6A methylation and stabilizing Stearoyl-CoA desaturase (SCD) via a YTHDF1-dependent manner. Keywords: Nonalcoholic fatty liver disease, LDHA, METTL3, YTHDF1, Histone lactylation." M6ADIS0107 39903889 . M6ACROT03135 REG00024 M6ATAR00388 Histone modification / Lactylation EPIREG00051 EPITAR00220 EPITAR00027 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "LDHA-induced Histone H3 lysine 18 lactylation (H3K18lac) promoted NAFLD progression, where LDHA-induced H3K18lac in METTL3 promoter elevated METTL3 expression, thereby promoting m6A methylation and stabilizing Stearoyl-CoA desaturase (SCD) via a YTHDF1-dependent manner. Keywords: Nonalcoholic fatty liver disease, LDHA, METTL3, YTHDF1, Histone lactylation." M6ADIS0107 39903889 . M6ACROT03136 REG00022 M6ATAR00140 Histone modification / Lactylation EPIREG00035 EPITAR00208 EPITAR00238 Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "Histone H3 lysine 18 lactylation (H3K18la) in HCC induces increased expression of YTHDC1, increasing the stability of m6A-modified Nuclear paraspeckle assembly transcript 1 (NEAT1). The histone acetyltransferase p300 is then recruited by NEAT1 and activates SCD by increasing the level of histone acetylation at the SCD promoter, thus facilitating HCC progression via hepatocellular lipid metabolism remodeling. Taken together, these discoveries suggest a close link between the epigenetic machinery and lipid metabolic abnormalities, which promotes cancer progression." M6ADIS0006 39725144 . M6ACROT03137 REG00022 M6ATAR00140 Histone modification / Acetylation EPIREG00035 EPITAR00203 EPITAR00558 Up regulation m6A Indirect Enhancement Histone modification m6A modification indirectly regulates histone modification through downstream signaling pathways "H3K18la in HCC induces increased expression of YTHDC1, increasing the stability of m6A-modified Nuclear paraspeckle assembly transcript 1 (NEAT1). The histone acetyltransferase p300 is then recruited by NEAT1 and activates SCD by increasing the level of Histone H3 lysine 27 acetylation (H3K27ac) at the SCD promoter, thus facilitating HCC progression via hepatocellular lipid metabolism remodeling. Taken together, these discoveries suggest a close link between the epigenetic machinery and lipid metabolic abnormalities, which promotes cancer progression." M6ADIS0006 39725144 . M6ACROT03138 REG00025 M6ATAR01622 Histone modification / Lactylation EPIREG00035 EPITAR00208 EPITAR00249 Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "p300 is responsible for catalyzing the H3K18ac modification. Histone H3 lysine 18 lactylation (H3K18la)-regulated YTHDF3 is involved in SEV-induced microglial pyroptosis. YTHDF3 stabilizes Thioredoxin-dependent peroxide reductase, mitochondrial (PRDX3) mRNA through m6A modification. H3K18la regulates YTHDF3/PRDX3 mediated pyroptosis to mitigating SEV-induced cognitive dysfunction in neonatal mice." M6ADIS0342 40022822 . M6ACROT03139 REG00006 M6ATAR00451 Histone modification / Methylation EPIREG00054 EPITAR00221 EPITAR00195 Down regulation Histone modification Direct Inhibition m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "METTL14 suppresses the expression of Transcriptional coactivator YAP1 (YAP1) in a YTHDF2 dependent manner. The loss of METTL14 expression results from KDM1A-mediated removal of Histone H3 lysine 4 dimethylation (H3K4me2) at the promoter region, which is critical for LSD1-driven stemness in TNBC." M6ADIS0184 39563370 . M6ACROT03140 REG00008 M6ATAR00451 Histone modification / Methylation EPIREG00054 EPITAR00221 EPITAR00195 Down regulation Histone modification Indirect Inhibition m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "METTL14 suppresses the expression of Transcriptional coactivator YAP1 (YAP1) in a YTHDF2 dependent manner. The loss of METTL14 expression results from KDM1A-mediated removal of Histone H3 lysine 4 dimethylation (H3K4me2) at the promoter region, which is critical for LSD1-driven stemness in TNBC." M6ADIS0184 39563370 . M6ACROT03141 REG00007 M6ATAR00140 Histone modification / Acetylation EPIREG00070 EPITAR00203 . Up regulation m6A Indirect Enhancement Histone modification m6A modification indirectly regulates histone modification through downstream signaling pathways The genome-protective role of Nuclear paraspeckle assembly transcript 1 (NEAT1) is mediated by the RNA methyltransferase 3 (METTL3) and involves the release of the chromodomain helicase DNA binding protein 4 (CHD4) from NEAT1 to fine-tune Histone H3 lysine 27 acetylation (H3K27ac) at DSBs. Our data suggest a direct role for NEAT1 in DDR. . 39362776 . M6ACROT03142 REG00007 . Histone modification / Methylation EPIREG00071 EPITAR00222 EPITAR00027 . Histone modification Direct Enhancement m6A Histone modification directly impacts m6A modification through modulating the level of m6A regulator "Histone H3 lysine 36 monomethylation (H3K36me1) plays an important role in HSCR, confirming that the methyltransferase SMYD2 can affect m6A methylation levels and intestinal nervous system development by regulating METTL3 expression." M6ADIS0374 39109795 . M6ACROT03143 REG00007 M6ATAR00197 Histone modification / Acetylation EPIREG00058 EPITAR00203 EPITAR00027 Down regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "CAT upregulated NRF1, NRF1 activated METTL3 via Kat2a transcription, and METTL3 inhibited Beclin-1 (BECN1) via m6A modification. KAT2A could increase the Histone H3 lysine 27 acetylation (H3K27ac) level in the METTL3 promoter region to activate METTL3 transcription." . 38773376 . M6ACROT03144 REG00007 M6ATAR01624 Histone modification / Acetylation EPIREG00067 . . Up regulation m6A Direct Enhancement Histone modification m6A modification impacts directly histone modification through modulating the expression level of histone-associated enzymes METTL3 determines endocrine lineage by modulating Histone deacetylase 1 (HDAC1) activity during the transition of bipotent progenitors might help in the development of targeted endocrine cell protocols for diabetes treatment. . 37963393 . M6ACROT03145 REG00052 M6ATAR01625 Histone modification / Lactylation EPIREG00072 EPITAR00208 . Down regulation m6A Indirect Inhibition Histone modification m6A modification indirectly regulates histone modification through downstream signaling pathways "METTL7B suppressed the expression of Ubiquitin carboxyl-terminal hydrolase 38 (USP38) via m6A dependent mRNA degradation, resulting in increasing ubiquitylation of HDAC3, which decreasing Histone H3 lysine 18 lactylation (H3K18la) and H4K5la level." . 40068772 . M6ACROT03146 REG00052 M6ATAR01625 Histone modification / Lactylation EPIREG00072 EPITAR00223 . Down regulation m6A Indirect Inhibition Histone modification m6A modification indirectly regulates histone modification through downstream signaling pathways "METTL7B suppressed the expression of Ubiquitin carboxyl-terminal hydrolase 38 (USP38) via m6A dependent mRNA degradation, resulting in increasing ubiquitylation of HDAC3, which decreasing H3K18la and Histone H4 lysine 5 lactylation (H4K5la) level." . 40068772 . M6ACROT03147 REG00007 M6ATAR01610 Histone modification / Acetylation EPIREG00058 . . Down regulation m6A Direct Inhibition Histone modification m6A modification impacts directly histone modification through modulating the expression level of histone-associated enzymes "METTL3 regulates the expression of Histone acetyltransferase KAT2A (KAT2A), a histone acetyltransferase, by methylating the m6A site in the 3'UTR of KAT2A mRNA in NSCLC cells. Intriguingly, NFIC was also found to negatively regulate the expression of KAT2A by directly binding to its promoter region." M6ADIS0007 38943137 . M6ACROT03148 REG00007 M6ATAR01626 Histone modification / Acetylation EPIREG00073 EPITAR00224 . Up regulation m6A Direct Enhancement Histone modification m6A modification impacts directly histone modification through modulating the expression level of histone-associated enzymes "Depletion of METTL3-mediated m6A modification leads to abnormally elongated cilia via suppressing Protein deacetylase HDAC6 (HDAC6)-dependent deacetylation of axonemal alpha-tubulin, ultimately attenuating cell growth and cervical cancer development." . 39535388 . M6ACROT03149 REG00007 M6ATAR00360 Histone modification / Methylation EPIREG00074 EPITAR00202 EPITAR00027 . Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "EHMT2 promotes m6A methyltransferase activity of METTL3, which upregulates Programmed cell death 1 ligand 1 (CD274/PD-L1), CX3CR1 and CASP1, at translational/post-translational level by regulating Histone H3 lysine 9 dimethylation (H3K9me2) level during ET." M6ADIS0125 37858336 . M6ACROT03150 REG00007 M6ATAR01369 Histone modification / Methylation EPIREG00074 EPITAR00202 EPITAR00027 . Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "EHMT2 promotes m6A methyltransferase activity of METTL3, which upregulates PD-L1, CX3C chemokine receptor 1 (CX3CR1) and CASP1, at translational/post-translational level by regulating Histone H3 lysine 9 dimethylation (H3K9me2) level during ET." M6ADIS0125 37858336 . M6ACROT03151 REG00007 M6ATAR01282 Histone modification / Methylation EPIREG00074 EPITAR00202 EPITAR00027 . Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "EHMT2 promotes m6A methyltransferase activity of METTL3, which upregulates PD-L1, CX3CR1 and Caspase-1 (CASP1), at translational/post-translational level by regulating Histone H3 lysine 9 dimethylation (H3K9me2) level during ET." M6ADIS0125 37858336 . M6ACROT03152 REG00006 M6ATAR01628 Histone modification / Acetylation . EPITAR00203 EPITAR00195 Up regulation Histone modification Direct Enhancement m6A Histone modification directly impacts m6A modification through modulating the level of m6A regulator "METTL14 catalysed m6A modification on Ankyrin repeat domain-containing protein 22 (ANKRD22) messenger ribonucleic acid (mRNA), recognized by the reader IGF2BP2, leading to increased mRNA stability and higher translational efficiency.our findings highlighted elevated ANKRD22-mediated Histone H3 lysine 27 acetylation (H3K27ac) signals near the METTL14 promoter, which contributes to a positive feedback loop perpetuating malignant progression in NPC." M6ADIS0054 39021049 . M6ACROT03153 REG00013 M6ATAR01628 Histone modification / Acetylation . EPITAR00203 EPITAR00195 Up regulation Histone modification Indirect Enhancement m6A Histone modification indirectly regulates m6A modification through downstream signaling pathways "METTL14 catalysed m6A modification on Ankyrin repeat domain-containing protein 22 (ANKRD22) messenger ribonucleic acid (mRNA), recognized by the reader IGF2BP2, leading to increased mRNA stability and higher translational efficiency.our findings highlighted elevated ANKRD22-mediated Histone H3 lysine 27 acetylation (H3K27ac) signals near the METTL14 promoter, which contributes to a positive feedback loop perpetuating malignant progression in NPC." M6ADIS0054 39021049 . M6ACROT03154 REG00005 M6ATAR00605 Histone modification / Lactylation . EPITAR00208 EPITAR00183 Down regulation Histone modification Direct Enhancement m6A Histone modification directly impacts m6A modification through modulating the level of m6A regulator "G6PT deficiency induces intracellular lactate accumulation, which enhances histone Histone H3 lysine 18 lactylation (H3K18la) and upregulates ALKBH5 expression; ALKBH5 demethylates m6A modification on NACHT, LRR and PYD domains-containing protein 3 (NLRP3) mRNA, leading to NLRP3 mRNA degradation and diminished inflammasome activation." . 39900266 . M6ACROT03155 REG00012 M6ATAR00341 Histone modification / Acetylation EPIREG00035 EPITAR00203 EPITAR00234 Up regulation Histone modification Direct Enhancement m6A Histone modification directly impacts m6A modification through modulating the level of m6A regulator "IGF2BP1 expression was upregulated by p300-mediated Histone H3 lysine 27 acetylation (H3K27ac) enrichment of its promoter, which positively correlated with poor clinicopathological characteristics and survival. IGF2BP1 not only regulated the Myc proto-oncogene protein (MYC)/p16 axis to promote iCCA growth and inhibit senescence, but also activated the ZIC2/PAK4/AKT/MMP2 axis to induce tumor metastasis. " M6ADIS0006 36736530 . M6ACROT03156 REG00006 M6ATAR01629 Histone modification / Methylation EPIREG00056 EPITAR00225 EPITAR00195 Down regulation Histone modification Direct Inhibition m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "JMJD6 affects METTL14 expression in an arginine Histone H4 arginine 3 symmetric dimethylation (H4R3me2a) dependent manner, and mediates m6A modification of Amino acid transporter heavy chain SLC3A2 (SLC3A2) to regulate its expression level, thereby affecting the sensitivity of lung cancer cells to ferroptosis" M6ADIS0007 40011892 . M6ACROT03157 REG00006 M6ATAR01630 Histone modification / Lactylation . EPITAR00208 EPITAR00195 Down regulation Histone modification Direct Enhancement m6A Histone modification directly impacts m6A modification through modulating the level of m6A regulator "Histone H3 lysine 18 lactylation (H3K18la) was found to upregulate METTL14 expression. In conclusion, METTL14 knockdown promotes stemness in GC by mediating m6A modification of Cyclic AMP-dependent transcription factor ATF-5 (ATF5) mRNA, which activates the WDR74/beta-catenin axis, making METTL14 a potential therapeutic target for gastric cancer treatment." M6ADIS0057 39497511 . M6ACROT03158 REG00020 . Histone modification / Acetylation EPIREG00072 EPITAR00226 . . Histone modification Direct Enhancement m6A Histone modification directly impacts m6A modification through recruiting m6A regulator "Lactate uptake mediated by Monocarboxylate transporter 1 (MCT1) is essential for RBM15 induction. Subsequent investigations revealed that L-lactate promotes lactylation of RBM15 majorly at Lys850 (K850), while histone deacetylase 3 (HDAC3) acts as the delactylase for RBM15. Importantly, lactylation of RBM15 stabilizes itself by inhibiting proteasome-mediated ubiquitin degradation. Mutation of the lactylation site K850R disrupts the association between RBM15 and METTL3, leading to a reduction in global m6A levels. Moreover, K850R significantly abrogated RBM15-mediated cell proliferation and migration in LUAD cells. Collectively, these findings unveil lactylation as a novel regulatory mechanism affecting both stability and m6A methylation activity of RBM15 in LUAD cells." M6ADIS0007 40135634 . M6ACROT03159 REG00005 M6ATAR00399 Histone modification / Methylation EPIREG00038 EPITAR00201 . Down regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "KDM4C decreases Histone H3 lysine 9 trimethylation (H3K9me3) methylation to upregulate ALKBH5 and subsequently inhibits Zinc finger protein SNAI1 (SNAI1), ultimately impeding liver fibrosis." M6ADIS0017 38938016 . M6ACROT03160 REG00007 M6ATAR01632 Histone modification / Methylation EPIREG00039 EPITAR00204 EPITAR00027 Down regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator KMT2A-mediated Histone H3 lysine 4 trimethylation (H3K4me3) regulates the autophagy-GATA4 axis through METTL3-mediated m6A modification of Cysteine protease ATG4A (ATG4A) in a YTHDF2 dependent manner to promote NPCs senescence and IVDD progression M6ADIS0168 39572532 . M6ACROT03161 REG00008 M6ATAR01632 Histone modification / Methylation EPIREG00039 EPITAR00204 EPITAR00027 Down regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways KMT2A-mediated Histone H3 lysine 4 trimethylation (H3K4me3) regulates the autophagy-GATA4 axis through METTL3-mediated m6A modification of Cysteine protease ATG4A (ATG4A) in a YTHDF2 dependent manner to promote NPCs senescence and IVDD progression M6ADIS0168 39572532 . M6ACROT03162 REG00022 M6ATAR01633 Histone modification / Methylation EPIREG00040 EPITAR00210 EPITAR00163 Up regulation m6A Direct Enhancement Histone modification m6A modification impacts directly histone modification through modulating the expression level of histone-associated enzymes YTHDC1 is a therapeutic target for B-cell acute lymphoblastic leukemia by attenuating DNA damage response through the Histone-lysine N-methyltransferase 2C (KMT2C)-Histone H3 lysine 4 monomethylation (H3K4me1)/H3K4me3 epigenetic axis. BRCA1 is a downstream gene of H3K4me1. M6ADIS0348 39501105 . M6ACROT03163 REG00022 M6ATAR01633 Histone modification / Methylation EPIREG00040 EPITAR00204 EPITAR00559 Up regulation m6A Direct Enhancement Histone modification m6A modification impacts directly histone modification through modulating the expression level of histone-associated enzymes YTHDC1 is a therapeutic target for B-cell acute lymphoblastic leukemia by attenuating DNA damage response through the Histone-lysine N-methyltransferase 2C (KMT2C)-H3K4me1/Histone H3 lysine 4 trimethylation (H3K4me3) epigenetic axis. RAD51 is a downstream gene of H3K4me3. M6ADIS0348 39501105 . M6ACROT03164 REG00008 M6ATAR01634 Histone modification / Acetylation EPIREG00075 EPITAR00227 EPITAR00479 Down regulation m6A Indirect Inhibition Histone modification m6A modification indirectly regulates histone modification through downstream signaling pathways YTHDF2-mediated degradation of m6A-modified Circ_SLC9A6 was found to be essential for the regulation of SLC9A6-126aa expression. Nuclear SLC9A6-126aa promotes transcriptional activation of the target gene CD36 and enhances its occupancy of the CD36 promoter locus by regulating KAT8-mediated histone Histone H4 lysine 16 acetylation (H4K16ac). M6ADIS0107 39107881 . M6ACROT03165 REG00007 M6ATAR01635 Histone modification / Methylation EPIREG00036 EPITAR00205 . Down regulation m6A Indirect Inhibition Histone modification m6A modification indirectly regulates histone modification through downstream signaling pathways "METTL3 deletion in the endometrium alters mRNA m6A methylation via Polycomb protein EED (EED) interaction. This reduces m6A recognized by YTHDC1, which recruits Eed to suppress EZH2-mediated Histone H3 lysine 27 trimethylation (H3K27me3) modification co-transcriptionally. The reduction of H3K27me3 disrupts chromatin accessibility and impairs transcription of genes critical for endometrial receptivity. Collectively, these results shed light on a Mettl3-Eed-m6A-Ythdc1 axis that links m6A and histone modification in regulating local chromatin state and gene expression, advancing our understanding of the epigenetic crosstalk between RNA and DNA modification in infertility disease." . 39934221 . M6ACROT03166 REG00007 . Histone modification / Acetylation . EPITAR00209 . . Histone modification Direct Enhancement m6A Histone modification directly impacts m6A modification through recruiting m6A regulator "METTL3 interacts with RNA polymerase II and active histone modifications such as Histone H3 lysine 9 acetylation (H3K9ac), H3K27ac, and H3K36me3 to maintain the expression of proteasome-related genes." M6ADIS0042 37456679 M6ADRUG0216 M6ACROT03167 REG00007 . Histone modification / Acetylation . EPITAR00203 . . Histone modification Direct Enhancement m6A Histone modification directly impacts m6A modification through recruiting m6A regulator "METTL3 interacts with RNA polymerase II and active histone modifications such as H3K9ac, Histone H3 lysine 27 acetylation (H3K27ac), and H3K36me3 to maintain the expression of proteasome-related genes." M6ADIS0042 37456679 M6ADRUG0216 M6ACROT03168 REG00007 . Histone modification / Methylation . EPITAR00206 . . Histone modification Direct Enhancement m6A Histone modification directly impacts m6A modification through recruiting m6A regulator "METTL3 interacts with RNA polymerase II and active histone modifications such as H3K9ac, H3K27ac, and Histone H3 lysine 36 trimethylation (H3K36me3) to maintain the expression of proteasome-related genes." M6ADIS0042 37456679 M6ADRUG0216 M6ACROT03169 REG00007 M6ATAR00578 Histone modification / Acetylation EPIREG00035 EPITAR00203 EPITAR00027 . Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "The transcription factor ETS1 recruited p300 and WDR5 which separately mediated Histone H3 lysine 27 acetylation (H3K27ac) and H3K4me3 histone modification in the promoter of METTL3 and induced METTL3 transcription activation. Furthermore, we identified Thioredoxin domain-containing protein 5 (TXNDC5) as a target of METTL3-mediated m6A modification through MeRIP-seq, and revealed that METTL3-mediated TXNDC5 expression relied on the m6A reader-dependent manner." M6ADIS0008 35987795 . M6ACROT03170 REG00007 M6ATAR00578 Histone modification / Methylation EPIREG00066 EPITAR00204 EPITAR00027 . Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "The transcription factor ETS1 recruited P300 and WDR5 which separately mediated H3K27ac and Histone H3 lysine 4 trimethylation (H3K4me3) histone modification in the promoter of METTL3 and induced METTL3 transcription activation. Furthermore, we identified Thioredoxin domain-containing protein 5 (TXNDC5) as a target of METTL3-mediated m6A modification through MeRIP-seq, and revealed that METTL3-mediated TXNDC5 expression relied on the m6A reader-dependent manner." M6ADIS0008 35987795 . M6ACROT03171 REG00008 M6ATAR00578 Histone modification / Acetylation EPIREG00035 EPITAR00203 EPITAR00027 . Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "The transcription factor ETS1 recruited p300 and WDR5 which separately mediated Histone H3 lysine 27 acetylation (H3K27ac) and H3K4me3 histone modification in the promoter of METTL3 and induced METTL3 transcription activation. Furthermore, we identified Thioredoxin domain-containing protein 5 (TXNDC5) as a target of METTL3-mediated m6A modification through MeRIP-seq, and revealed that METTL3-mediated TXNDC5 expression relied on YTHDF2-dependent manner." M6ADIS0008 35987795 . M6ACROT03172 REG00008 M6ATAR00578 Histone modification / Methylation EPIREG00066 EPITAR00204 EPITAR00027 . Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "The transcription factor ETS1 recruited P300 and WDR5 which separately mediated H3K27ac and Histone H3 lysine 4 trimethylation (H3K4me3) histone modification in the promoter of METTL3 and induced METTL3 transcription activation. Furthermore, we identified Thioredoxin domain-containing protein 5 (TXNDC5) as a target of METTL3-mediated m6A modification through MeRIP-seq, and revealed that METTL3-mediated TXNDC5 expression relied on YTHDF2-dependent manner." M6ADIS0008 35987795 . M6ACROT03173 REG00020 M6ATAR00516 Histone modification / Acetylation EPIREG00035 EPITAR00203 EPITAR00226 Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "Epigenetic activation of RBM15 promotes clear cell renal cell carcinoma growth, metastasis and macrophage infiltration by regulating the m6A modification of C-X-C motif chemokine 11 (CXCL11). Enhanced RBM15 was caused by the abundant Histone H3 lysine 27 acetylation (H3K27ac)/H3K9ac of the RBM15 promoter induced by p300/CBP." M6ADIS0010 35381326 M6ADRUG0214 M6ACROT03174 REG00020 M6ATAR00516 Histone modification / Acetylation EPIREG00035 EPITAR00209 EPITAR00226 Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "Epigenetic activation of RBM15 promotes clear cell renal cell carcinoma growth, metastasis and macrophage infiltration by regulating the m6A modification of C-X-C motif chemokine 11 (CXCL11). Enhanced RBM15 was caused by the abundant H3K27ac/Histone H3 lysine 9 acetylation (H3K9ac) of the RBM15 promoter induced by p300/CBP." M6ADIS0010 35381326 M6ADRUG0214 M6ACROT03175 REG00020 M6ATAR00516 Histone modification / Acetylation EPIREG00034 EPITAR00203 EPITAR00226 Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "Epigenetic activation of RBM15 promotes clear cell renal cell carcinoma growth, metastasis and macrophage infiltration by regulating the m6A modification of C-X-C motif chemokine 11 (CXCL11). Enhanced RBM15 was caused by the abundant Histone H3 lysine 27 acetylation (H3K27ac)/H3K9ac of the RBM15 promoter induced by EP300/CREBBP." M6ADIS0010 35381326 M6ADRUG0214 M6ACROT03176 REG00020 M6ATAR00516 Histone modification / Acetylation EPIREG00034 EPITAR00209 EPITAR00226 Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "Epigenetic activation of RBM15 promotes clear cell renal cell carcinoma growth, metastasis and macrophage infiltration by regulating the m6A modification of C-X-C motif chemokine 11 (CXCL11). Enhanced RBM15 was caused by the abundant H3K27ac/Histone H3 lysine 9 acetylation (H3K9ac) of the RBM15 promoter induced by EP300/CREBBP." M6ADIS0010 35381326 M6ADRUG0214 M6ACROT03177 REG00007 M6ATAR01477 Histone modification / Methylation EPIREG00054 EPITAR00201 EPITAR00027 Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "KDM1A-mediated upregulation of METTL3, which is caused by the abundant Histone H3 lysine 9 trimethylation (H3K9me3), ameliorates Alzheimer's disease via enhancing autophagic clearance of p-Tau through m6A-dependent regulation of E3 ubiquitin-protein ligase CHIP (STUB1)." M6ADIS0089 36587923 . M6ACROT03178 REG00022 M6ATAR01635 Histone modification / Methylation EPIREG00036 EPITAR00205 . Down regulation m6A Indirect Inhibition Histone modification m6A modification indirectly regulates histone modification through downstream signaling pathways "METTL3 deletion in the endometrium alters mRNA m6A methylation via Polycomb protein EED (EED) interaction. This reduces m6A recognized by YTHDC1, which recruits Eed to suppress EZH2-mediated Histone H3 lysine 27 trimethylation (H3K27me3) modification co-transcriptionally. The reduction of H3K27me3 disrupts chromatin accessibility and impairs transcription of genes critical for endometrial receptivity. Collectively, these results shed light on a Mettl3-Eed-m6A-Ythdc1 axis that links m6A and histone modification in regulating local chromatin state and gene expression, advancing our understanding of the epigenetic crosstalk between RNA and DNA modification in infertility disease." . 39934221 . M6ACROT03179 REG00001 M6ATAR01460 Histone modification / Methylation EPIREG00060 EPITAR00201 EPITAR00176 Down regulation m6A Direct Inhibition Histone modification m6A modification impacts directly histone modification through modulating the expression level of histone-associated enzymes "FTO deletion and METTL16 overexpression significantly increased m6A levels. This led to the downregulation of the methyltransferase Histone-lysine N-methyltransferase SUV39H1 (SUV39H1), resulting in reduced Histone H3 lysine 9 trimethylation (H3K9me3) expression, which activated LTR7 and LTR12, subsequently activating ERV1." M6ADIS0094 39410722 . M6ACROT03180 REG00017 M6ATAR01460 Histone modification / Methylation EPIREG00060 EPITAR00201 EPITAR00176 Up regulation m6A Direct Enhancement Histone modification m6A modification impacts directly histone modification through modulating the expression level of histone-associated enzymes "FTO deletion and METTL16 overexpression significantly increased m6A levels. This led to the downregulation of the methyltransferase Histone-lysine N-methyltransferase SUV39H1 (SUV39H1), resulting in reduced Histone H3 lysine 9 trimethylation (H3K9me3) expression, which activated LTR7 and LTR12, subsequently activating ERV1." M6ADIS0094 39410722 . M6ACROT03181 REG00009 M6ATAR00939 Histone modification / Methylation EPIREG00041 EPITAR00201 . Down regulation m6A Direct Inhibition Histone modification m6A modification impacts directly histone modification through modulating the expression level of histone-associated enzymes "Pharmacological or genetic intervention in the HIF1alpha-WTAP axis results in the reduction of m6A level on Lysine-specific demethylase 4B (KDM4B) transcripts and increased its degradation, correlated with lower expression of KDM4B and higher trimethylation levels of Histone H3 lysine 9 trimethylation (H3K9me3)." M6ADIS0046 37087529 . M6ACROT03182 REG00007 M6ATAR00637 Histone modification / Methylation EPIREG00020 EPITAR00204 EPITAR00027 Down regulation Histone modification Direct Inhibition m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "Methylcytosine dioxygenase TET1 (TET1) knockdown contributed to the binding of Histone H3 lysine 4 trimethylation (H3K4me3) and H3K27me3 to METTL3 DNA. Our results revealed a negative feedback regulatory loop between TET1 and METTL3/YTHDF2 in myoblast differentiation, which unveiled the interplay among DNA methylation, RNA methylation and histone methylation in skeletal myogenesis." . 36375665 . M6ACROT03183 REG00007 M6ATAR00637 Histone modification / Methylation EPIREG00020 EPITAR00205 EPITAR00027 Down regulation Histone modification Direct Inhibition m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "Methylcytosine dioxygenase TET1 (TET1) knockdown contributed to the binding of H3K4me3 and Histone H3 lysine 27 trimethylation (H3K27me3) to METTL3 DNA. Our results revealed a negative feedback regulatory loop between TET1 and METTL3/YTHDF2 in myoblast differentiation, which unveiled the interplay among DNA methylation, RNA methylation and histone methylation in skeletal myogenesis." . 36375665 . M6ACROT03184 REG00008 M6ATAR00637 Histone modification / Methylation EPIREG00020 EPITAR00204 EPITAR00027 Down regulation Histone modification Indirect Inhibition m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "Methylcytosine dioxygenase TET1 (TET1) knockdown contributed to the binding of Histone H3 lysine 4 trimethylation (H3K4me3) and H3K27me3 to METTL3 DNA. Our results revealed a negative feedback regulatory loop between TET1 and METTL3/YTHDF2 in myoblast differentiation, which unveiled the interplay among DNA methylation, RNA methylation and histone methylation in skeletal myogenesis." . 36375665 . M6ACROT03185 REG00008 M6ATAR00637 Histone modification / Methylation EPIREG00020 EPITAR00205 EPITAR00027 Down regulation Histone modification Indirect Inhibition m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "Methylcytosine dioxygenase TET1 (TET1) knockdown contributed to the binding of H3K4me3 and Histone H3 lysine 27 trimethylation (H3K27me3) to METTL3 DNA. Our results revealed a negative feedback regulatory loop between TET1 and METTL3/YTHDF2 in myoblast differentiation, which unveiled the interplay among DNA methylation, RNA methylation and histone methylation in skeletal myogenesis." . 36375665 . M6ACROT03186 REG00025 M6ATAR01636 Histone modification / Methylation EPIREG00076 EPITAR00201 EPITAR00480 Down regulation m6A Direct Inhibition Histone modification m6A modification impacts directly histone modification through modulating the expression level of histone-associated enzymes "The m6A-modified Chromobox protein homolog 1 (CBX1) mRNA transcript is recognized and destabilized by the m6A reader YTHDF3. Furthermore, it is revealed that CBX1 promotes NPC cell migration, invasion, and proliferation through transcriptional repression of MAP7 via Histone H3 lysine 9 trimethylation (H3K9me3)-mediated heterochromatin formation." M6ADIS0054 36310139 . M6ACROT03187 REG00007 M6ATAR01383 Histone modification / Acetylation EPIREG00077 EPITAR00228 EPITAR00481 Up regulation m6A Direct Enhancement Histone modification m6A modification impacts directly histone modification through modulating the expression level of histone-associated enzymes PM exposure increased the expression of histone deacetylase 9 (Histone deacetylase 9 (HDAC9)) in human bronchial epithelial cells and mouse airway epithelium through the METTL3/m6A methylation/IGF2BP3 pathway. HDAC9 modulated the deacetylation of Histone H4 lysine 12 acetylation (H4K12ac) in the promoter region of DUSP9 to repress the expression of DUSP9 and resulting in the activation of MAPK signaling pathway M6ADIS0397 39088948 . M6ACROT03188 REG00014 M6ATAR01383 Histone modification / Acetylation EPIREG00077 EPITAR00228 EPITAR00481 Up regulation m6A Direct Enhancement Histone modification m6A modification impacts directly histone modification through modulating the expression level of histone-associated enzymes PM exposure increased the expression of histone deacetylase 9 (Histone deacetylase 9 (HDAC9)) in human bronchial epithelial cells and mouse airway epithelium through the METTL3/m6A methylation/IGF2BP3 pathway. HDAC9 modulated the deacetylation of Histone H4 lysine 12 acetylation (H4K12ac) in the promoter region of DUSP9 to repress the expression of DUSP9 and resulting in the activation of MAPK signaling pathway M6ADIS0397 39088948 . M6ACROT03189 REG00005 M6ATAR00768 Histone modification / Acetylation EPIREG00057 EPITAR00184 . Up regulation m6A Direct Enhancement Histone modification m6A modification impacts directly histone modification through modulating the expression level of histone-associated enzymes "ALKBH5 demethylates and stabilizes Hdac4 mRNA. Histone deacetylase 4 (HDAC4) interacts with and deacetylates Forkhead box protein O3 (FOXO3), resulting in a significant increase in FoxO3 expression" M6ADIS0135 35142084 . M6ACROT03190 REG00007 M6ATAR01496 Histone modification / Methylation EPIREG00061 EPITAR00201 EPITAR00482 Up regulation m6A Direct Enhancement Histone modification m6A modification impacts directly histone modification through modulating the expression level of histone-associated enzymes "METTL3-mediated m6A modification promotes mRNA stability of Histone-lysine N-methyltransferase SUV39H2 (SUV39H2) in an IGF2BP2 dependent manner, resulting in upregulated mRNA expression of SUV39H2. As a histone methyltransferase, SUV39H2 was verified to increase the phosphorylation level of ATM through transcriptional repression of DUSP6 by modulating Histone H3 lysine 9 trimethylation (H3K9me3) levels, thereby promoting HRR and ultimately inhibiting GC chemosensitivity to cisplatin." M6ADIS0057 36806557 M6ADRUG0047 M6ACROT03191 REG00013 M6ATAR01496 Histone modification / Methylation EPIREG00061 EPITAR00201 EPITAR00482 Up regulation m6A Direct Enhancement Histone modification m6A modification impacts directly histone modification through modulating the expression level of histone-associated enzymes "METTL3-mediated m6A modification promotes mRNA stability of Histone-lysine N-methyltransferase SUV39H2 (SUV39H2) in an IGF2BP2 dependent manner, resulting in upregulated mRNA expression of SUV39H2. As a histone methyltransferase, SUV39H2 was verified to increase the phosphorylation level of ATM through transcriptional repression of DUSP6 by modulating Histone H3 lysine 9 trimethylation (H3K9me3) levels, thereby promoting HRR and ultimately inhibiting GC chemosensitivity to cisplatin." M6ADIS0057 36806557 M6ADRUG0047 M6ACROT03192 REG00022 M6ATAR00860 Histone modification / Methylation EPIREG00032 EPITAR00202 EPITAR00022 Up regulation m6A Indirect Enhancement Histone modification m6A modification indirectly regulates histone modification through downstream signaling pathways "m6A-modified ATP8B1 antisense RNA 1 (ATP8B1-AS1) interacts with and recruits m6A reader YTHDC1 and histone demethylase KDM3B to MYC promoter region, leading to the reduction of Histone H3 lysine 9 dimethylation (H3K9me2) level at MYC promoter region and activation of MYC transcription." M6ADIS0006 37701563 . M6ACROT03193 REG00018 . Histone modification / Methylation . EPITAR00205 . . m6A Indirect Enhancement Histone modification m6A modification indirectly regulates histone modification through downstream signaling pathways "Inhibition of METTL5 reduced the activity of phosphorylated ribosomal protein S6, decreased the levels of the repressive histone modification Histone H3 lysine 27 trimethylation (H3K27me3) and increased the expression of activating histone modifications H3K27ac and H3K4me3 and mRNA levels of some 2-cell-specific genes." . 36111643 . M6ACROT03194 REG00018 . Histone modification / Acetylation . EPITAR00203 . . m6A Indirect Enhancement Histone modification m6A modification indirectly regulates histone modification through downstream signaling pathways "Inhibition of METTL5 reduced the activity of phosphorylated ribosomal protein S6, decreased the levels of the repressive histone modification H3K27me3 and increased the expression of activating histone modifications Histone H3 lysine 27 acetylation (H3K27ac) and H3K4me3 and mRNA levels of some 2-cell-specific genes." . 36111643 . M6ACROT03195 REG00018 . Histone modification / Methylation . EPITAR00204 . . m6A Indirect Enhancement Histone modification m6A modification indirectly regulates histone modification through downstream signaling pathways "Inhibition of METTL5 reduced the activity of phosphorylated ribosomal protein S6, decreased the levels of the repressive histone modification H3K27me3 and increased the expression of activating histone modifications H3K27ac and Histone H3 lysine 4 trimethylation (H3K4me3) and mRNA levels of some 2-cell-specific genes." . 36111643 . M6ACROT03196 REG00009 M6ATAR01637 Histone modification / Methylation EPIREG00078 EPITAR00205 EPITAR00483 Up regulation m6A Indirect Enhancement Histone modification m6A modification indirectly regulates histone modification through downstream signaling pathways "WTAP act as an N6-methyladenosine transferase to regulate the m6A modification of long noncoding RNA testis expressed 41 (TEX41). Then, the upregulated m6A modification destabilized TEX41 in a YTHDF2-dependent manner. Furthermore, TEX41 interacted with the SUZ12 protein and increased the histone methyltransferase activity of SUZ12, resulting in HDAC1 silencing by Histone H3 lysine 27 trimethylation (H3K27me3). " M6ADIS0010 39433619 . M6ACROT03197 REG00008 M6ATAR01637 Histone modification / Methylation EPIREG00078 EPITAR00205 EPITAR00483 Up regulation m6A Indirect Enhancement Histone modification m6A modification indirectly regulates histone modification through downstream signaling pathways "WTAP act as an N6-methyladenosine transferase to regulate the m6A modification of long noncoding RNA testis expressed 41 (TEX41). Then, the upregulated m6A modification destabilized TEX41 in a YTHDF2-dependent manner. Furthermore, TEX41 interacted with the SUZ12 protein and increased the histone methyltransferase activity of SUZ12, resulting in HDAC1 silencing by Histone H3 lysine 27 trimethylation (H3K27me3). " M6ADIS0010 39433619 . M6ACROT03198 REG00001 M6ATAR00976 Histone modification / Methylation EPIREG00053 EPITAR00221 . Up regulation m6A Direct Enhancement Histone modification m6A modification impacts directly histone modification through modulating the expression level of histone-associated enzymes FTO-mediated Lysine-specific demethylase 5B (KDM5B) stabilization in the context of loss of Smad4 activate DLG1/YAP1 pathway by modulating Histone H3 lysine 4 dimethylation (H3K4me2)/H3K4me3 levels to promote tumorigenesis by reprogramming lipid accumulation in PDAC. M6ADIS0061 38789418 . M6ACROT03199 REG00001 M6ATAR00976 Histone modification / Methylation EPIREG00053 EPITAR00204 . Up regulation m6A Direct Enhancement Histone modification m6A modification impacts directly histone modification through modulating the expression level of histone-associated enzymes FTO-mediated Lysine-specific demethylase 5B (KDM5B) stabilization in the context of loss of Smad4 activate DLG1/YAP1 pathway by modulating H3K4me2/Histone H3 lysine 4 trimethylation (H3K4me3) levels to promote tumorigenesis by reprogramming lipid accumulation in PDAC. M6ADIS0061 38789418 . M6ACROT03200 REG00012 M6ATAR00249 Histone modification / Methylation EPIREG00036 EPITAR00205 . Up regulation m6A Direct Enhancement Histone modification m6A modification impacts directly histone modification through modulating the expression level of histone-associated enzymes "IGF2BP1 promotes neuroendocrine tumor cell proliferation by stabilizing the mRNA of Histone-lysine N-methyltransferase EZH2 (EZH2), the catalytic subunit of PRC2, which represses gene expression by tri-methylation of Histone H3 lysine 27 trimethylation (H3K27me3)." M6ADIS0160 35565249 . M6ACROT03201 REG00005 M6ATAR01638 Histone modification / Methylation EPIREG00066 EPITAR00204 EPITAR00183 Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "Mechanically, the highly expressed ALKBH5 is induced by HBV encodes X protein (HBX)-mediated Histone H3 lysine 4 trimethylation (H3K4me3) modification of ALKBH5 gene promoter in a WDR5-dependent manner after HBV infection. The increased ALKBH5 protein catalyzes the m6A demethylation of HBx mRNA, thus stabilizing and favoring a higher HBx expression level." M6ADIS0006 34112124 . M6ACROT03202 REG00005 M6ATAR01011 Histone modification / Methylation EPIREG00074 EPITAR00202 EPITAR00484 Up regulation m6A Indirect Enhancement Histone modification m6A modification indirectly regulates histone modification through downstream signaling pathways "ALKBH5 removed m6A modification to stabilize Taurine up-regulated 1 protein (TUG1) expression in a YTHDF2-dependent manner, enhancing EHMT2-mediated Histone H3 lysine 9 dimethylation (H3K9me2) levels on the SH3BGRL promoter and suppressing SH3BGRL expression, thus promoting ADR resistance in AML cells." M6ADIS0046 39465506 M6ADRUG0251 M6ACROT03203 REG00008 M6ATAR01011 Histone modification / Methylation EPIREG00074 EPITAR00202 EPITAR00484 Down regulation m6A Indirect Inhibition Histone modification m6A modification indirectly regulates histone modification through downstream signaling pathways "ALKBH5 removed m6A modification to stabilize Taurine up-regulated 1 protein (TUG1) expression in a YTHDF2-dependent manner, enhancing EHMT2-mediated Histone H3 lysine 9 dimethylation (H3K9me2) levels on the SH3BGRL promoter and suppressing SH3BGRL expression, thus promoting ADR resistance in AML cells." M6ADIS0046 39465506 M6ADRUG0251 M6ACROT03204 REG00007 M6ATAR00990 Histone modification / Methylation EPIREG00079 EPITAR00204 EPITAR00551 Up regulation m6A Direct Enhancement Histone modification m6A modification impacts directly histone modification through modulating the expression level of histone-associated enzymes "METTL3 promoted the expression of Histone-lysine N-methyltransferase ASH1L (ASH1L) via enhancing its stability in a YT521-B homology domain containing 2 (YTHDC2)-dependent manner, which further decreased the expression of IL17RA and IL-23R by modulating Histone H3 lysine 4 trimethylation (H3K4me3) levels, resulting in reduced pathogenic Th17 responses." M6ADIS0182 36753389 . M6ACROT03205 REG00023 M6ATAR00990 Histone modification / Methylation EPIREG00079 EPITAR00204 EPITAR00551 Up regulation m6A Direct Enhancement Histone modification m6A modification impacts directly histone modification through modulating the expression level of histone-associated enzymes "METTL3 promoted the expression of Histone-lysine N-methyltransferase ASH1L (ASH1L) via enhancing its stability in a YT521-B homology domain containing 2 (YTHDC2)-dependent manner, which further decreased the expression of IL17RA and IL-23R by modulating Histone H3 lysine 4 trimethylation (H3K4me3) levels, resulting in reduced pathogenic Th17 responses." M6ADIS0182 36753389 . M6ACROT03206 REG00006 M6ATAR01639 Histone modification / Acetylation EPIREG00072 . . Up regulation m6A Direct Enhancement Histone modification m6A modification impacts directly histone modification through modulating the expression level of histone-associated enzymes "METTL14 induced Histone deacetylase 3 (HDAC3) m6A modification in an IGF2BP3-dependent manner, and could activate cGAS-STING pathway through HDAC3." M6ADIS0091 39448421 . M6ACROT03207 REG00014 M6ATAR01639 Histone modification / Acetylation EPIREG00072 . . Up regulation m6A Direct Enhancement Histone modification m6A modification impacts directly histone modification through modulating the expression level of histone-associated enzymes "METTL14 induced Histone deacetylase 3 (HDAC3) m6A modification in an IGF2BP3-dependent manner, and could activate cGAS-STING pathway through HDAC3." M6ADIS0091 39448421 . M6ACROT03208 REG00004 M6ATAR01090 Histone modification / Acetylation EPIREG00035 EPITAR00203 EPITAR00486 Up regulation Histone modification Direct Enhancement m6A histone modification regulates m6A modification through both regulatory proteins targeting the same gene "LINC00355 binds to p300 histone acetyltransferase, specifying Histone H3 lysine 27 acetylation (H3K27ac) modification pattern on the Cell division control protein 42 homolog (CDC42) promoter to activate CDC42 transcription, thereby altering GC cell biology. In addition, HNRNPA2B1, which is upregulated by LINC00355, recognizes the N6-methyladenosine (m6A) sites of CDC42 and enhances the stability of CDC42 mRNA transcripts. Therefore, LINC00355 is mechanistically, functionally, and clinically oncogenic in GC cells." M6ADIS0057 37983727 . M6ACROT03209 REG00007 M6ATAR01640 Histone modification / Methylation EPIREG00080 EPITAR00218 . Up regulation m6A Direct Enhancement Histone modification m6A modification impacts directly histone modification through modulating the expression level of histone-associated enzymes "METTL3 promoted m6A modification of Histone-lysine N-methyltransferase NSD2 (NSD2) mRNA and enhanced its stability by YTHDF1. Moreover, NSD2 catalyzes Histone H3 lysine 36 dimethylation (H3K36me2) , playing a crucial role in chromatin regulation and transcriptional control." M6ADIS0117 35354439 . M6ACROT03210 REG00024 M6ATAR01640 Histone modification / Methylation EPIREG00080 EPITAR00218 . Up regulation m6A Direct Enhancement Histone modification m6A modification impacts directly histone modification through modulating the expression level of histone-associated enzymes "METTL3 promoted m6A modification of Histone-lysine N-methyltransferase NSD2 (NSD2) mRNA and enhanced its stability by YTHDF1 . Moreover, NSD2 catalyzes tHistone H3 lysine 36 dimethylation (H3K36me2) , playing a crucial role in chromatin regulation and transcriptional control." M6ADIS0117 35354439 . M6ACROT03211 REG00007 M6ATAR01640 Histone modification / Methylation EPIREG00080 EPITAR00206 . Up regulation m6A Direct Enhancement Histone modification m6A modification impacts directly histone modification through modulating the expression level of histone-associated enzymes "METTL3 promoted m6A modification of Histone-lysine N-methyltransferase NSD2 (NSD2) mRNA and enhanced its stability by YTHDF1. Moreover, NSD2 catalyzes tHistone H3 lysine 36 trimethylation (H3K36me3) , playing a crucial role in chromatin regulation and transcriptional control." M6ADIS0117 35354439 . M6ACROT03212 REG00024 M6ATAR01640 Histone modification / Methylation EPIREG00080 EPITAR00206 . Up regulation m6A Direct Enhancement Histone modification m6A modification impacts directly histone modification through modulating the expression level of histone-associated enzymes "METTL3 promoted m6A modification of Histone-lysine N-methyltransferase NSD2 (NSD2) mRNA and enhanced its stability by YTHDF1 . Moreover, NSD2 catalyzes tHistone H3 lysine 36 trimethylation (H3K36me3) , playing a crucial role in chromatin regulation and transcriptional control." M6ADIS0117 35354439 . M6ACROT03213 REG00025 M6ATAR00297 Histone modification / Methylation EPIREG00053 EPITAR00204 EPITAR00487 . Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "KDM5B demethylated Histone H3 lysine 4 trimethylation (H3K4me3) on the MIR448 promoter and thereby inhibited the expression of miR-448, which in turn targeted YTHDF3 and Integrin alpha-6 (ITGA6) to promote the malignant phenotype of HCC. Moreover, KDM5B accelerated HCC progression in nude mice via the miR-448/YTHDF3/ITGA6 axis. " M6ADIS0006 33829656 . M6ACROT03214 REG00022 M6ATAR00854 Histone modification / Methylation EPIREG00032 EPITAR00202 EPITAR00102 Up regulation m6A Indirect Enhancement Histone modification m6A modification indirectly regulates histone modification through downstream signaling pathways "m6A-modified Long non-coding RNA epigenetically activating Wnt/beta-catenin signalling in HCC (LEAWBIH) activated Wnt/beta-catenin signaling. m6A-modified LEAWBIH binds to the m6A reader YTHDC1, which further interacts with and recruits Histone H3 lysine 9 dimethylation (H3K9me2) demethylase KDM3B to CTNNB1 promoter, leading to H3K9me2 demethylation and CTNNB1 transcription activation. Functional rescue assays showed that blocking Wnt/beta-catenin signaling abolished the role of LEAWBIH in HCC." M6ADIS0006 37954496 . M6ACROT03215 REG00008 M6ATAR00298 Histone modification / Acetylation EPIREG00081 EPITAR00203 EPITAR00232 Down regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "HAT1 activated the transcription activity of YTHDF2 through Histone H3 lysine 27 acetylation (H3K27ac) of the promoter, and YTHDF2 triggered the instability of Integrin beta-1 (ITGB1) mRNA to induce mRNA degradation in an m6A manner." M6ADIS0015 34098071 . M6ACROT03216 REG00020 M6ATAR01641 Histone modification / Methylation EPIREG00039 EPITAR00204 EPITAR00226 Down regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "KMT2A elevated RBM15 expression by increasing Histone H3 lysine 4 trimethylation (H3K4me3) on RBM15 promoter. RBM15 promoted the binding of Tripartite motif-containing protein 72 (TRIM72) to YTHDF2 by enhancing m6A modification on TRIM72 mRNA, thereby repressing TRIM72 expression. TRIM72 bound to ADAM9 and ubiquitinated it for degradation. " M6ADIS0311 39709463 M6ADRUG0250 M6ACROT03217 REG00008 M6ATAR01641 Histone modification / Methylation EPIREG00039 EPITAR00204 EPITAR00226 Down regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "KMT2A elevated RBM15 expression by increasing Histone H3 lysine 4 trimethylation (H3K4me3) on RBM15 promoter. RBM15 promoted the binding of Tripartite motif-containing protein 72 (TRIM72) to YTHDF2 by enhancing m6A modification on TRIM72 mRNA, thereby repressing TRIM72 expression. TRIM72 bound to ADAM9 and ubiquitinated it for degradation. " M6ADIS0311 39709463 M6ADRUG0250 M6ACROT03218 REG00024 M6ATAR01146 Histone modification / Acetylation EPIREG00034 . . Up regulation m6A Direct Enhancement Histone modification m6A modification impacts directly histone modification through modulating the expression level of histone-associated enzymes "The metabolite beta-hydroxybutyrate (BHBA) secreted after acute exercise upregulates m6A modification in WAT. This enhances YTHDF1/YTHDF2-dependent translation of the histone acetyltransferase CREB-binding protein (CREBBP), promoting the transcription of key beiging genes by increasing chromatin accessibility. " . 39581460 M6ADRUG0217 M6ACROT03219 REG00008 M6ATAR01146 Histone modification / Acetylation EPIREG00034 . . Up regulation m6A Direct Enhancement Histone modification m6A modification impacts directly histone modification through modulating the expression level of histone-associated enzymes "The metabolite beta-hydroxybutyrate (BHBA) secreted after acute exercise upregulates m6A modification in WAT. This enhances YTHDF1/YTHDF2-dependent translation of the histone acetyltransferase CREB-binding protein (CREBBP), promoting the transcription of key beiging genes by increasing chromatin accessibility. " . 39581460 M6ADRUG0217 M6ACROT03220 REG00024 M6ATAR01642 Histone modification / Ubiquitination EPIREG00082 EPITAR00207 . Down regulation m6A Direct Inhibition Histone modification m6A modification impacts directly histone modification through modulating the expression level of histone-associated enzymes "YTHDF1, the N6-methyladenine (m6A) RNA reader that was previously known to be mainly cytoplasmic, associates with E3 ubiquitin-protein ligase RING2 (RNF2), a PRC1 protein that mediates Histone H2A lysine 119 ubiquitination (H2AK119ub) in human embryonic stem cells (hESCs)." . 37991435 . M6ACROT03221 REG00008 M6ATAR00375 Histone modification / Methylation EPIREG00036 EPITAR00205 EPITAR00488 Down regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways Histone methyltransferase EZH2 inhibited hsa-miR-454-3p through Histone H3 lysine 27 trimethylation (H3K27me3) and promoted m6A modification of Mutated in multiple advanced cancers 1 (PTEN)/MYC/UBXN1/NF-Kappa-B to induce glioma M2 macrophage polarization. miR-454-3p promoted PTEN expression by inhibiting m6A modification through binding to the enzyme YTHDF2 M6ADIS0001 33363140 . M6ACROT03222 REG00007 M6ATAR00802 Histone modification / Acetylation EPIREG00035 EPITAR00203 EPITAR00489 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "LINC01605 was regulated by SMYD2-p300-mediated modifications of histone H3K4me3 as well as Histone H3 lysine 27 acetylation (H3K27ac). LINC01605 was found to bind to METTL3 and promote the m6A modification ofSpectrin beta, non-erythrocytic 2 (SPTBN2) mRNA, thereby facilitating the translation of SPTBN2." M6ADIS0059 34544413 . M6ACROT03223 REG00007 M6ATAR00802 Histone modification / Methylation EPIREG00071 EPITAR00204 EPITAR00489 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "LINC01605 was regulated by SMYD2-EP300-mediated modifications of histone Histone H3 lysine 4 trimethylation (H3K4me3) as well as H3K27ac. LINC01605 was found to bind to METTL3 and promote the m6A modification ofSpectrin beta, non-erythrocytic 2 (SPTBN2) mRNA, thereby facilitating the translation of SPTBN2." M6ADIS0059 34544413 . M6ACROT03224 REG00009 M6ATAR01643 Histone modification / Methylation EPIREG00050 EPITAR00205 . Up regulation m6A Indirect Enhancement Histone modification m6A modification indirectly regulates histone modification through downstream signaling pathways "Knockdown of PHD finger protein 19 (PHF19) precipitates loss of Histone H3 lysine 27 trimethylation (H3K27me3) modulated by PRC2 and enhanced chromatin accessibility, ultimately resulting in upregulated expression of genes involved in the cell cycle and DNA damage checkpoints. Therefore, WTAP/m6A-dependent PHF19 upregulation accelerates leukemia progression by coordinating m6A modification and histone methylation, establishing its status as a novel therapeutic target for t(8; 21) AML." M6ADIS0307 40038518 . M6ACROT03225 REG00007 M6ATAR01644 Histone modification / Lactylation EPIREG00035 EPITAR00230 EPITAR00027 Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "p300-mediated Histone H3 lysine 9 lactylation (H3K9la) in the promoter region of the N6-methyladenosine (m6A) writer METTL3 was enriched to enhance METTL3 transcription, leading to the Lnc668 m6A modification. Meanwhile, the m6A reader YTHDC1 recognized m6A-modified lnc668 and elevated the METTL3-mediated lnc668 modification. " M6ADIS0310 40221424 . M6ACROT03226 REG00022 M6ATAR01644 Histone modification / Lactylation EPIREG00035 EPITAR00230 EPITAR00027 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "p300-mediated Histone H3 lysine 9 lactylation (H3K9la) in the promoter region of the N6-methyladenosine (m6A) writer METTL3 was enriched to enhance METTL3 transcription, leading to the Lnc668 m6A modification. Meanwhile, the m6A reader YTHDC1 recognized m6A-modified lnc668 and elevated the METTL3-mediated lnc668 modification. " M6ADIS0310 40221424 . M6ACROT03227 REG00009 M6ATAR00939 Histone modification / Methylation EPIREG00041 . . Up regulation m6A Direct Enhancement Histone modification m6A modification impacts directly histone modification through modulating the expression level of histone-associated enzymes "In t(8; 21) AML cell lines, WTAP could regulate the expression of Lysine-specific demethylase 4B (KDM4B) by regulating the m6A modification of the 3'UTR of KDM4B mRNA, and silencing the expression of KDM4B could inhibit the cellular proliferation in vitro." M6ADIS0307 38660840 . M6ACROT03228 REG00007 M6ATAR00569 Histone modification / Methylation EPIREG00036 EPITAR00205 EPITAR00490 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "Collectively, EZH2 downregulated hsa-miR-338-5p through Histone H3 lysine 27 trimethylation (H3K27me3), which in turn impaired miR-338-5p-dependent METTL3 inhibition and enhanced CUB domain-containing protein 1 (CDCP1) translation, therefore contributing to the development of GC." M6ADIS0057 33882457 . M6ACROT03229 REG00006 M6ATAR01277 Histone modification / Methylation EPIREG00084 EPITAR00204 EPITAR00195 Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "PHF20 elevated METTL14 expression by enhancing the enrichment of Histone H3 lysine 4 trimethylation (H3K4me3) on its promoter, and METTL14 strengthened Homeobox protein Hox-A13 (HOXA13) m6A methylation to maintain HOXA13 mRNA stability through IGF2BP3. In conclusion, PHF20 elevates METTL14 expression by enhancing H3K4me3 enrichment on its promoter and enhances HOXA13 mRNA stability via IGF2BP3-mediated m6A modification, thus facilitating HOXA13 expression and eventually inducing osteogenic differentiation of BMSCs." . 39757292 . M6ACROT03230 REG00014 M6ATAR01277 Histone modification / Methylation EPIREG00084 EPITAR00204 EPITAR00195 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "PHF20 elevated METTL14 expression by enhancing the enrichment of Histone H3 lysine 4 trimethylation (H3K4me3) on its promoter, and METTL14 strengthened Homeobox protein Hox-A13 (HOXA13) m6A methylation to maintain HOXA13 mRNA stability through IGF2BP3. In conclusion, PHF20 elevates METTL14 expression by enhancing H3K4me3 enrichment on its promoter and enhances HOXA13 mRNA stability via IGF2BP3-mediated m6A modification, thus facilitating HOXA13 expression and eventually inducing osteogenic differentiation of BMSCs." . 39757292 . M6ACROT03231 REG00001 M6ATAR00669 Histone modification / Methylation EPIREG00074 EPITAR00202 EPITAR00491 Up regulation m6A Indirect Enhancement Histone modification m6A modification indirectly regulates histone modification through downstream signaling pathways "Peripheral nerve injury increases the expression of the m6A demethylase fat-mass and obesity-associated proteins (FTO) in the injured DRG via the activation of Runx1, a transcription factor that binds to the Fto gene promoter. Mimicking this increase erases m6A in euchromatic Histone-lysine N-methyltransferase EHMT2 (EHMT2) mRNA (encoding the histone methyltransferase G9a) and elevates the level of G9a (regulating Histone H3 lysine 9 dimethylation (H3K9me2) level) in DRG and leads to the upregulation of OPRM1. Conversely, blocking this increase reverses a loss of m6A sites in Ehmt2 mRNA and destabilizes the nerve injury-induced G9a upregulation in the injured DRG and alleviates nerve injury-associated pain hypersensitivities. FTO contributes to neuropathic pain likely through stabilizing nerve injury-induced upregulation of G9a in a YTHDF2 dependent manner, a neuropathic pain initiator, in primary sensory neurons." M6ADIS0161 32670741 . M6ACROT03232 REG00008 M6ATAR00669 Histone modification / Methylation EPIREG00074 EPITAR00202 EPITAR00491 Down regulation m6A Indirect Inhibition Histone modification m6A modification indirectly regulates histone modification through downstream signaling pathways "Peripheral nerve injury increases the expression of the m6A demethylase fat-mass and obesity-associated proteins (FTO) in the injured DRG via the activation of Runx1, a transcription factor that binds to the Fto gene promoter. Mimicking this increase erases m6A in euchromatic Histone-lysine N-methyltransferase EHMT2 (EHMT2) mRNA (encoding the histone methyltransferase G9a) and elevates the level of G9a (regulating Histone H3 lysine 9 dimethylation (H3K9me2) level) in DRG and leads to the upregulation of OPRM1. Conversely, blocking this increase reverses a loss of m6A sites in Ehmt2 mRNA and destabilizes the nerve injury-induced G9a upregulation in the injured DRG and alleviates nerve injury-associated pain hypersensitivities. FTO contributes to neuropathic pain likely through stabilizing nerve injury-induced upregulation of G9a in a YTHDF2 dependent manner, a neuropathic pain initiator, in primary sensory neurons." M6ADIS0161 32670741 . M6ACROT03233 REG00007 M6ATAR01646 Histone modification / Methylation EPIREG00066 EPITAR00204 EPITAR00492 Up regulation m6A Indirect Enhancement Histone modification m6A modification indirectly regulates histone modification through downstream signaling pathways "Pirin (PIR) expression is driven by aberrant N6-methyladenosine (m6A) modifications mediated by METTL3 and IGF2BP3. Meanwhile, the high expressed PIR acts as a transcriptional co-regulator by interacting with WDR5, resulting in the regulation of Histone H3 lysine 4 trimethylation (H3K4me3) modifications at the ANAPC10 promoter region and subsequent promotion of ANAPC10 expression." M6ADIS0072 40252822 . M6ACROT03234 REG00014 M6ATAR01646 Histone modification / Methylation EPIREG00066 EPITAR00204 EPITAR00492 Up regulation m6A Indirect Enhancement Histone modification m6A modification indirectly regulates histone modification through downstream signaling pathways "Pirin (PIR) expression is driven by aberrant N6-methyladenosine (m6A) modifications mediated by METTL3 and IGF2BP3. Meanwhile, the high expressed PIR acts as a transcriptional co-regulator by interacting with WDR5, resulting in the regulation of Histone H3 lysine 4 trimethylation (H3K4me3) modifications at the ANAPC10 promoter region and subsequent promotion of ANAPC10 expression." M6ADIS0072 40252822 . M6ACROT03235 REG00005 M6ATAR00976 Histone modification / Methylation EPIREG00053 EPITAR00204 EPITAR00493 Up regulation m6A Direct Enhancement Histone modification m6A modification impacts directly histone modification through modulating the expression level of histone-associated enzymes "Lysine-specific demethylase 5B (KDM5B) and RBBP5, the components of H3K4 modifying enzyme complexes, are identified as downstream targets for ALKBH5 in cardiac-committed hESCs. Loss of function of ALKBH5 alters the expression of KDM5B and RBBP5 through impairing stability of their mRNAs, which in turn promotes the transcription of GATA4 by enhancing Histone H3 lysine 4 trimethylation (H3K4me3) at the promoter region of GATA4." . 34513291 . M6ACROT03236 REG00005 M6ATAR01300 Histone modification / Methylation EPIREG00085 EPITAR00204 EPITAR00493 Up regulation m6A Direct Enhancement Histone modification m6A modification impacts directly histone modification through modulating the expression level of histone-associated enzymes "KDM5B and Retinoblastoma-binding protein 5 (RBBP5), the components of H3K4 modifying enzyme complexes, are identified as downstream targets for ALKBH5 in cardiac-committed hESCs. Loss of function of ALKBH5 alters the expression of KDM5B and RBBP5 through impairing stability of their mRNAs, which in turn promotes the transcription of GATA4 by enhancing Histone H3 lysine 4 trimethylation (H3K4me3) at the promoter region of GATA4." . 34513291 . M6ACROT03237 REG00005 M6ATAR00592 Histone modification / Methylation EPIREG00032 EPITAR00202 EPITAR00494 Down regulation m6A Indirect Inhibition Histone modification m6A modification indirectly regulates histone modification through downstream signaling pathways "Inhibition of ALKBH5 promotes KDM3B-mediated ALCAM demethylation by facilitating Peroxisome proliferator-activated receptor gamma (PPARG) mRNA m6A modification, and further activates the Wnt/beta-catenin pathway, and in turn alleviates PE progression. PPARG repressed the Histone H3 lysine 9 dimethylation (H3K9me2) levels at activated leukocyte cell adhesion molecule (ALCAM) promoter region by increasing the expression and activity of lysine demethylase 3B (KDM3B). " M6ADIS0311 34995009 . M6ACROT03238 REG00008 M6ATAR00260 Histone modification / Acetylation EPIREG00034 . EPITAR00495 Down regulation m6A Indirect Inhibition Histone modification m6A modification indirectly regulates histone modification through downstream signaling pathways "ROS exposure activated YTHDF2 and promoted the degradation of m6A-modified Forkhead box protein O3 (FOXO3) mRNA, impairing FOXO3's ability to activate TIMP1.FOXO3 recruited histone acetyltransferase CREBBP (CREB binding protein) and mediator complex subunit 1 (Med1) to activate TIMP1 expression, which inhibited MMP activity and prevented disc degeneration." M6ADIS0168 39625652 . M6ACROT03239 REG00007 M6ATAR01264 Histone modification / Methylation EPIREG00037 EPITAR00205 EPITAR00496 Down regulation m6A Direct Inhibition Histone modification m6A modification impacts directly histone modification through modulating the expression level of histone-associated enzymes METTL3 induced Histone H3 lysine 27 trimethylation (H3K27me3) of the SLC7A11 promoter by suppressing the mRNA stability of H3K27 demethylases Lysine-specific demethylase 6B (KDM6B) in a YTHDF2 manner. . 39800682 . M6ACROT03240 REG00008 M6ATAR01264 Histone modification / Methylation EPIREG00037 EPITAR00205 EPITAR00496 Down regulation m6A Direct Inhibition Histone modification m6A modification impacts directly histone modification through modulating the expression level of histone-associated enzymes METTL3 induced Histone H3 lysine 27 trimethylation (H3K27me3) of the SLC7A11 promoter by suppressing the mRNA stability of H3K27 demethylases Lysine-specific demethylase 6B (KDM6B) in a YTHDF2 manner. . 39800682 . M6ACROT03241 REG00006 . Histone modification / Methylation EPIREG00086 EPITAR00205 EPITAR00195 Down regulation Histone modification Indirect Enhancement m6A Histone modification indirectly regulates m6A modification through downstream signaling pathways Histone H3 lysine 27 trimethylation (H3K27me3) Inhibition by KDM6A Induces METTL14-Mediated Decay of m6A-Marked Severe Acute Respiratory Syndrome Coronavirus 2 Transcripts. . 40183255 M6ADRUG0254 M6ACROT03242 REG00006 . Histone modification / Methylation EPIREG00037 EPITAR00205 EPITAR00195 Down regulation Histone modification Indirect Enhancement m6A Histone modification indirectly regulates m6A modification through downstream signaling pathways Histone H3 lysine 27 trimethylation (H3K27me3) Inhibition by KDM6B Induces METTL14-Mediated Decay of m6A-Marked Severe Acute Respiratory Syndrome Coronavirus 2 Transcripts. . 40183255 M6ADRUG0254 M6ACROT03243 REG00006 . Histone modification / Methylation EPIREG00087 EPITAR00205 EPITAR00195 Down regulation Histone modification Indirect Inhibition m6A Histone modification indirectly regulates m6A modification through downstream signaling pathways Histone H3 lysine 27 trimethylation (H3K27me3) Inhibition by knockout of EZH1 Induces METTL14-Mediated Decay of m6A-Marked Severe Acute Respiratory Syndrome Coronavirus 2 Transcripts. . 40183255 M6ADRUG0254 M6ACROT03244 REG00006 . Histone modification / Methylation EPIREG00036 EPITAR00205 EPITAR00195 Down regulation Histone modification Indirect Inhibition m6A Histone modification indirectly regulates m6A modification through downstream signaling pathways Histone H3 lysine 27 trimethylation (H3K27me3) Inhibition by knockout of EZH2 Induces METTL14-Mediated Decay of m6A-Marked Severe Acute Respiratory Syndrome Coronavirus 2 Transcripts. . 40183255 M6ADRUG0254 M6ACROT03245 REG00008 . Histone modification / Methylation EPIREG00086 EPITAR00205 EPITAR00195 Down regulation Histone modification Indirect Enhancement m6A Histone modification indirectly regulates m6A modification through downstream signaling pathways Histone H3 lysine 27 trimethylation (H3K27me3) Inhibition by KDM6A leads to the upregulation of METTL14 expression and Induces YTHDF2-Mediated Decay of m6A-Marked Severe Acute Respiratory Syndrome Coronavirus 2 Transcripts. . 40183255 M6ADRUG0254 M6ACROT03246 REG00008 . Histone modification / Methylation EPIREG00037 EPITAR00205 EPITAR00195 Down regulation Histone modification Indirect Enhancement m6A Histone modification indirectly regulates m6A modification through downstream signaling pathways Histone H3 lysine 27 trimethylation (H3K27me3) Inhibition by KDM6B leads to the upregulation of METTL14 expression and Induces YTHDF2-Mediated Decay of m6A-Marked Severe Acute Respiratory Syndrome Coronavirus 2 Transcripts. . 40183255 M6ADRUG0254 M6ACROT03247 REG00008 . Histone modification / Methylation EPIREG00087 EPITAR00205 EPITAR00195 Down regulation Histone modification Indirect Inhibition m6A Histone modification indirectly regulates m6A modification through downstream signaling pathways Histone H3 lysine 27 trimethylation (H3K27me3) Inhibition by knockout of EZH1 leads to the upregulation of METTL14 expression and Induces YTHDF2-Mediated Decay of m6A-Marked Severe Acute Respiratory Syndrome Coronavirus 2 Transcripts. . 40183255 M6ADRUG0254 M6ACROT03248 REG00008 . Histone modification / Methylation EPIREG00036 EPITAR00205 EPITAR00195 Down regulation Histone modification Indirect Inhibition m6A Histone modification indirectly regulates m6A modification through downstream signaling pathways Histone H3 lysine 27 trimethylation (H3K27me3) Inhibition by knockout of EZH2 leads to the upregulation of METTL14 expression and Induces YTHDF2-Mediated Decay of m6A-Marked Severe Acute Respiratory Syndrome Coronavirus 2 Transcripts. . 40183255 M6ADRUG0254 M6ACROT03249 REG00007 M6ATAR00759 Histone modification / Methylation EPIREG00088 EPITAR00204 EPITAR00497 Up regulation m6A Indirect Enhancement Histone modification m6A modification indirectly regulates histone modification through downstream signaling pathways "Chromobox protein homolog 8 (CBX8) activate the transcription of LGR5 in a noncanonical manner with assistance of Pol II. CBX8 recruited KMT2B to the LGR5 promoter, which maintained Histone H3 lysine 4 trimethylation (H3K4me3) status to promote LGR5 expression. Moreover, METTL3-mediated m6A methylation participated in the upregulation of CBX8 by maintaining CBX8 mRNA stability." M6ADIS0058 31849331 . M6ACROT03250 REG00023 M6ATAR01647 Histone modification / Methylation EPIREG00039 EPITAR00204 EPITAR00498 Up regulation m6A Direct Enhancement Histone modification m6A modification directly impacts histone modification through recruiting histone-associated enzymes "NUTM2B antisense RNA 1 (NUTM2B-AS1) specifically binds to BMPR1A promoter. m6A-methylated NUTM2B-AS1 is recognized by the m6A reader YTHDC2, which further binds to the H3K4 METTL3 and METTL16 induce m6A hypermethylation of NUTM2B-AS1. m6A-methylated NUTM2B-AS1 recruits YTHDC2 and KMT2A to BMPR1A promoter, leading to increased Histone H3 lysine 4 trimethylation (H3K4me3) and chromatin accessibility at BMPR1A promoter. Functional rescue assays suggest that BMPR1A is a critical mediator of the oncogenic role of m6A-methylated NUTM2B-AS1 in HCC." M6ADIS0006 39649245 . M6ACROT03251 REG00007 M6ATAR01647 Histone modification / Methylation EPIREG00039 EPITAR00204 EPITAR00498 Up regulation m6A Indirect Enhancement Histone modification m6A modification indirectly regulates histone modification through downstream signaling pathways "NUTM2B antisense RNA 1 (NUTM2B-AS1) specifically binds to BMPR1A promoter. m6A-methylated NUTM2B-AS1 is recognized by the m6A reader YTHDC2, which further binds to the H3K4 METTL3 and METTL16 induce m6A hypermethylation of NUTM2B-AS1. m6A-methylated NUTM2B-AS1 recruits YTHDC2 and KMT2A to BMPR1A promoter, leading to increased Histone H3 lysine 4 trimethylation (H3K4me3) and chromatin accessibility at BMPR1A promoter. Functional rescue assays suggest that BMPR1A is a critical mediator of the oncogenic role of m6A-methylated NUTM2B-AS1 in HCC." M6ADIS0006 39649245 . M6ACROT03252 REG00017 M6ATAR01647 Histone modification / Methylation EPIREG00039 EPITAR00204 EPITAR00498 Up regulation m6A Indirect Enhancement Histone modification m6A modification indirectly regulates histone modification through downstream signaling pathways "NUTM2B antisense RNA 1 (NUTM2B-AS1) specifically binds to BMPR1A promoter. m6A-methylated NUTM2B-AS1 is recognized by the m6A reader YTHDC2, which further binds to the H3K4 METTL3 and METTL16 induce m6A hypermethylation of NUTM2B-AS1. m6A-methylated NUTM2B-AS1 recruits YTHDC2 and KMT2A to BMPR1A promoter, leading to increased Histone H3 lysine 4 trimethylation (H3K4me3) and chromatin accessibility at BMPR1A promoter. Functional rescue assays suggest that BMPR1A is a critical mediator of the oncogenic role of m6A-methylated NUTM2B-AS1 in HCC." M6ADIS0006 39649245 . M6ACROT03253 REG00007 M6ATAR00688 Histone modification / Acetylation EPIREG00089 EPITAR00209 EPITAR00081 Up regulation m6A Direct Enhancement Histone modification m6A modification impacts directly histone modification through modulating the expression level of histone-associated enzymes "METTL3 upregulated histone deacetylase 5 (Histone deacetylase 5 (HDAC5)) expression in OS cells by increasing the m6A level. HDAC5 reduced the enrichment of Histone H3 lysine 9 acetylation (H3K9ac)/H3K14ac on MIR142 promoter, thus suppressing miR-142-5p expression and upregulating armadillo-repeat-containing 8 (ARMC8) level." M6ADIS0051 35396379 . M6ACROT03254 REG00007 M6ATAR00688 Histone modification / Acetylation EPIREG00089 EPITAR00231 EPITAR00081 Up regulation m6A Direct Enhancement Histone modification m6A modification impacts directly histone modification through modulating the expression level of histone-associated enzymes "METTL3 upregulated histone deacetylase 5 (Histone deacetylase 5 (HDAC5)) expression in OS cells by increasing the m6A level. HDAC5 reduced the enrichment of H3K9ac/Histone H3 lysine 14 acetylation (H3K14ac) on MIR142 promoter, thus suppressing miR-142-5p expression and upregulating armadillo-repeat-containing 8 (ARMC8) level." M6ADIS0051 35396379 . M6ACROT03255 REG00023 M6ATAR00976 Histone modification / Methylation EPIREG00053 EPITAR00204 EPITAR00562 Down regulation m6A Direct Inhibition Histone modification m6A modification impacts directly histone modification through modulating the expression level of histone-associated enzymes "YTHDC2 over expression decreased Lysine-specific demethylase 5B (KDM5B) mRNA stability in an m6A-dependent manner. Our results also revealed that YTHDC2 overexpression resulted in reduced ROS level and increased ATP level, PDH activity, OCR and ECAR in HG-treated Schwann cells, while these effects were reversed by KDM5B overexpression. KDM5B inhibited SIRT3 transcription by Histone H3 lysine 4 trimethylation (H3K4me3)." M6ADIS0117 36574062 . M6ACROT03256 REG00005 M6ATAR00422 Histone modification / Methylation EPIREG00038 EPITAR00201 EPITAR00183 Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "KDM4C regulates ALKBH5 expression via increasing chromatin accessibility of ALKBH5 locus, by reducing Histone H3 lysine 9 trimethylation (H3K9me3) levels and promoting recruitment of MYB and Pol II. Moreover, ALKBH5 affects mRNA stability of receptor tyrosine kinase AXL in an m6A-dependent way. ALKBH5 exerts tumor-promoting effects in acute myeloid leukemia by post-transcriptional regulation of its critical targets such as Transforming acidic coiled-coil-containing protein 3 (TACC3), a prognosis-associated oncogene in various cancers. " M6ADIS0046 32402251; 35579750 . M6ACROT03257 REG00005 M6ATAR00159 Histone modification / Methylation EPIREG00038 EPITAR00201 EPITAR00183 Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "KDM4C regulates ALKBH5 expression via increasing chromatin accessibility of ALKBH5 locus, by reducing Histone H3 lysine 9 trimethylation (H3K9me3) levels and promoting recruitment of MYB and Pol II. Moreover, ALKBH5 affects mRNA stability of receptor tyrosine kinase AXL in an m6A-dependent way. Bioactive peptides can inhibit acute myeloid leukemia cell proliferation by downregulating ALKBH5-mediated m6A demethylation of eIF4E-binding protein 1 (4EBP1/EIF4EBP1) and MLST8 mRNAs, which have potential to prevent and treat this disease." M6ADIS0046 32402251; 35579750 . M6ACROT03258 REG00005 M6ATAR00682 Histone modification / Methylation EPIREG00038 EPITAR00201 EPITAR00183 Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "KDM4C regulates ALKBH5 expression via increasing chromatin accessibility of ALKBH5 locus, by reducing Histone H3 lysine 9 trimethylation (H3K9me3) levels and promoting recruitment of MYB and Pol II. Moreover, ALKBH5 affects mRNA stability of receptor tyrosine kinase AXL in an m6A-dependent way. Bioactive peptides can inhibit acute myeloid leukemia cell proliferation by downregulating ALKBH5-mediated m6A demethylation of EIF4EBP1 and Target of rapamycin complex subunit LST8 (MLST8) mRNAs, which have potential to prevent and treat this disease." M6ADIS0046 32402251; 35579750 . M6ACROT03259 REG00005 M6ATAR01054 Histone modification / Methylation EPIREG00038 EPITAR00201 EPITAR00183 Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "KDM4C regulates ALKBH5 expression via increasing chromatin accessibility of ALKBH5 locus, by reducing Histone H3 lysine 9 trimethylation (H3K9me3) levels and promoting recruitment of MYB and Pol II. Moreover, ALKBH5 affects mRNA stability of receptor tyrosine kinase AXL in an m6A-dependent way. RNA demethylase ALKBH5 promotes tumorigenesis of t (8; 21) acute myeloid leukemia via Inosine triphosphate pyrophosphatase (ITPA) m6A modification" M6ADIS0046 32402251; 36899424 . M6ACROT03260 REG00005 M6ATAR00422 Histone modification / Methylation EPIREG00039 EPITAR00204 EPITAR00183 Up regulation Histone modification Direct Inhibition m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "KMT2A regulates ALKBH5 expression via decreasing chromatin accessibility of ALKBH5 locus, by reducing Histone H3 lysine 4 trimethylation (H3K4me3) levels and promoting recruitment of MYB and Pol II. Moreover, ALKBH5 affects mRNA stability of receptor tyrosine kinase AXL in an m6A-dependent way. ALKBH5 exerts tumor-promoting effects in acute myeloid leukemia by post-transcriptional regulation of its critical targets such as Transforming acidic coiled-coil-containing protein 3 (TACC3), a prognosis-associated oncogene in various cancers. " M6ADIS0046 32402251; 32402250 . M6ACROT03261 REG00005 M6ATAR00159 Histone modification / Methylation EPIREG00039 EPITAR00204 EPITAR00183 Up regulation Histone modification Direct Inhibition m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "KMT2A regulates ALKBH5 expression via decreasing chromatin accessibility of ALKBH5 locus, by reducing Histone H3 lysine 4 trimethylation (H3K4me3) levels and promoting recruitment of MYB and Pol II. Moreover, ALKBH5 affects mRNA stability of receptor tyrosine kinase AXL in an m6A-dependent way. Bioactive peptides can inhibit acute myeloid leukemia cell proliferation by downregulating ALKBH5-mediated m6A demethylation of eIF4E-binding protein 1 (4EBP1/EIF4EBP1) and MLST8 mRNAs, which have potential to prevent and treat this disease." M6ADIS0046 32402251; 35579750 . M6ACROT03262 REG00005 M6ATAR00682 Histone modification / Methylation EPIREG00039 EPITAR00204 EPITAR00183 Up regulation Histone modification Direct Inhibition m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "KMT2A regulates ALKBH5 expression via decreasing chromatin accessibility of ALKBH5 locus, by reducing Histone H3 lysine 4 trimethylation (H3K4me3) levels and promoting recruitment of MYB and Pol II. Moreover, ALKBH5 affects mRNA stability of receptor tyrosine kinase AXL in an m6A-dependent way. Bioactive peptides can inhibit acute myeloid leukemia cell proliferation by downregulating ALKBH5-mediated m6A demethylation of EIF4EBP1 and Target of rapamycin complex subunit LST8 (MLST8) mRNAs, which have potential to prevent and treat this disease." M6ADIS0046 32402251; 35579750 . M6ACROT03263 REG00005 M6ATAR01054 Histone modification / Methylation EPIREG00039 EPITAR00204 EPITAR00183 Up regulation Histone modification Direct Inhibition m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "KMT2A regulates ALKBH5 expression via decreasing chromatin accessibility of ALKBH5 locus, by reducing Histone H3 lysine 4 trimethylation (H3K4me3) levels and promoting recruitment of MYB and Pol II. Moreover, ALKBH5 affects mRNA stability of receptor tyrosine kinase AXL in an m6A-dependent way. RNA demethylase ALKBH5 promotes tumorigenesis of t (8; 21) acute myeloid leukemia via Inosine triphosphate pyrophosphatase (ITPA) m6A modification" M6ADIS0046 32402251; 36899424 . M6ACROT03264 REG00005 M6ATAR00422 Histone modification / Methylation EPIREG00040 EPITAR00204 EPITAR00183 Up regulation Histone modification Direct Inhibition m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "KMT2C regulates ALKBH5 expression via decreasing chromatin accessibility of ALKBH5 locus, by reducing Histone H3 lysine 4 trimethylation (H3K4me3) levels and promoting recruitment of MYB and Pol II. Moreover, ALKBH5 affects mRNA stability of receptor tyrosine kinase AXL in an m6A-dependent way. ALKBH5 exerts tumor-promoting effects in acute myeloid leukemia by post-transcriptional regulation of its critical targets such as Transforming acidic coiled-coil-containing protein 3 (TACC3), a prognosis-associated oncogene in various cancers. " M6ADIS0046 32402251; 32402250 . M6ACROT03265 REG00005 M6ATAR00159 Histone modification / Methylation EPIREG00040 EPITAR00204 EPITAR00183 Up regulation Histone modification Direct Inhibition m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "KMT2C regulates ALKBH5 expression via decreasing chromatin accessibility of ALKBH5 locus, by reducing Histone H3 lysine 4 trimethylation (H3K4me3) levels and promoting recruitment of MYB and Pol II. Moreover, ALKBH5 affects mRNA stability of receptor tyrosine kinase AXL in an m6A-dependent way. Bioactive peptides can inhibit acute myeloid leukemia cell proliferation by downregulating ALKBH5-mediated m6A demethylation of eIF4E-binding protein 1 (4EBP1/EIF4EBP1) and MLST8 mRNAs, which have potential to prevent and treat this disease." M6ADIS0046 32402251; 35579750 . M6ACROT03266 REG00005 M6ATAR00682 Histone modification / Methylation EPIREG00040 EPITAR00204 EPITAR00183 Up regulation Histone modification Direct Inhibition m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "KMT2C regulates ALKBH5 expression via decreasing chromatin accessibility of ALKBH5 locus, by reducing Histone H3 lysine 4 trimethylation (H3K4me3) levels and promoting recruitment of MYB and Pol II. Moreover, ALKBH5 affects mRNA stability of receptor tyrosine kinase AXL in an m6A-dependent way. Bioactive peptides can inhibit acute myeloid leukemia cell proliferation by downregulating ALKBH5-mediated m6A demethylation of EIF4EBP1 and Target of rapamycin complex subunit LST8 (MLST8) mRNAs, which have potential to prevent and treat this disease." M6ADIS0046 32402251; 35579750 . M6ACROT03267 REG00005 M6ATAR01054 Histone modification / Methylation EPIREG00040 EPITAR00204 EPITAR00183 Up regulation Histone modification Direct Inhibition m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "KMT2C regulates ALKBH5 expression via decreasing chromatin accessibility of ALKBH5 locus, by reducing Histone H3 lysine 4 trimethylation (H3K4me3) levels and promoting recruitment of MYB and Pol II. Moreover, ALKBH5 affects mRNA stability of receptor tyrosine kinase AXL in an m6A-dependent way. RNA demethylase ALKBH5 promotes tumorigenesis of t (8; 21) acute myeloid leukemia via Inosine triphosphate pyrophosphatase (ITPA) m6A modification" M6ADIS0046 32402251; 36899424 . M6ACROT03268 REG00005 M6ATAR00422 Histone modification / Methylation EPIREG00041 EPITAR00201 EPITAR00183 Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "KDM4B regulates ALKBH5 expression via increasing chromatin accessibility of ALKBH5 locus, by reducing Histone H3 lysine 9 trimethylation (H3K9me3) levels and promoting recruitment of MYB and Pol II. Moreover, ALKBH5 affects mRNA stability of receptor tyrosine kinase AXL in an m6A-dependent way. ALKBH5 exerts tumor-promoting effects in acute myeloid leukemia by post-transcriptional regulation of its critical targets such as Transforming acidic coiled-coil-containing protein 3 (TACC3), a prognosis-associated oncogene in various cancers. " M6ADIS0046 32402251; 32402250 . M6ACROT03269 REG00005 M6ATAR00159 Histone modification / Methylation EPIREG00041 EPITAR00201 EPITAR00183 Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "KDM4B regulates ALKBH5 expression via increasing chromatin accessibility of ALKBH5 locus, by reducing Histone H3 lysine 9 trimethylation (H3K9me3) levels and promoting recruitment of MYB and Pol II. Moreover, ALKBH5 affects mRNA stability of receptor tyrosine kinase AXL in an m6A-dependent way. Bioactive peptides can inhibit acute myeloid leukemia cell proliferation by downregulating ALKBH5-mediated m6A demethylation of eIF4E-binding protein 1 (4EBP1/EIF4EBP1) and MLST8 mRNAs, which have potential to prevent and treat this disease." M6ADIS0046 32402251; 35579750 . M6ACROT03270 REG00005 M6ATAR00682 Histone modification / Methylation EPIREG00041 EPITAR00201 EPITAR00183 Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "KDM4B regulates ALKBH5 expression via increasing chromatin accessibility of ALKBH5 locus, by reducing Histone H3 lysine 9 trimethylation (H3K9me3) levels and promoting recruitment of MYB and Pol II. Moreover, ALKBH5 affects mRNA stability of receptor tyrosine kinase AXL in an m6A-dependent way. Bioactive peptides can inhibit acute myeloid leukemia cell proliferation by downregulating ALKBH5-mediated m6A demethylation of EIF4EBP1 and Target of rapamycin complex subunit LST8 (MLST8) mRNAs, which have potential to prevent and treat this disease." M6ADIS0046 32402251; 35579750 . M6ACROT03271 REG00005 M6ATAR01054 Histone modification / Methylation EPIREG00041 EPITAR00201 EPITAR00183 Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "KDM4B regulates ALKBH5 expression via increasing chromatin accessibility of ALKBH5 locus, by reducing Histone H3 lysine 9 trimethylation (H3K9me3) levels and promoting recruitment of MYB and Pol II. Moreover, ALKBH5 affects mRNA stability of receptor tyrosine kinase AXL in an m6A-dependent way. RNA demethylase ALKBH5 promotes tumorigenesis of t (8; 21) acute myeloid leukemia via Inosine triphosphate pyrophosphatase (ITPA) m6A modification" M6ADIS0046 32402251; 36899424 . M6ACROT03272 REG00005 M6ATAR00422 Histone modification / Methylation EPIREG00042 EPITAR00201 EPITAR00183 Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "JMJD1C regulates ALKBH5 expression via increasing chromatin accessibility of ALKBH5 locus, by reducing Histone H3 lysine 9 trimethylation (H3K9me3) levels and promoting recruitment of MYB and Pol II. Moreover, ALKBH5 affects mRNA stability of receptor tyrosine kinase AXL in an m6A-dependent way. ALKBH5 exerts tumor-promoting effects in acute myeloid leukemia by post-transcriptional regulation of its critical targets such as Transforming acidic coiled-coil-containing protein 3 (TACC3), a prognosis-associated oncogene in various cancers. " M6ADIS0046 32402251; 32402250 . M6ACROT03273 REG00005 M6ATAR00159 Histone modification / Methylation EPIREG00042 EPITAR00201 EPITAR00183 Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "JMJD1C regulates ALKBH5 expression via increasing chromatin accessibility of ALKBH5 locus, by reducing Histone H3 lysine 9 trimethylation (H3K9me3) levels and promoting recruitment of MYB and Pol II. Moreover, ALKBH5 affects mRNA stability of receptor tyrosine kinase AXL in an m6A-dependent way. Bioactive peptides can inhibit acute myeloid leukemia cell proliferation by downregulating ALKBH5-mediated m6A demethylation of eIF4E-binding protein 1 (4EBP1/EIF4EBP1) and MLST8 mRNAs, which have potential to prevent and treat this disease." M6ADIS0046 32402251; 35579750 . M6ACROT03274 REG00005 M6ATAR00682 Histone modification / Methylation EPIREG00042 EPITAR00201 EPITAR00183 Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "JMJD1C regulates ALKBH5 expression via increasing chromatin accessibility of ALKBH5 locus, by reducing Histone H3 lysine 9 trimethylation (H3K9me3) levels and promoting recruitment of MYB and Pol II. Moreover, ALKBH5 affects mRNA stability of receptor tyrosine kinase AXL in an m6A-dependent way. Bioactive peptides can inhibit acute myeloid leukemia cell proliferation by downregulating ALKBH5-mediated m6A demethylation of EIF4EBP1 and Target of rapamycin complex subunit LST8 (MLST8) mRNAs, which have potential to prevent and treat this disease." M6ADIS0046 32402251; 35579750 . M6ACROT03275 REG00005 M6ATAR01054 Histone modification / Methylation EPIREG00042 EPITAR00201 EPITAR00183 Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "JMJD1C regulates ALKBH5 expression via increasing chromatin accessibility of ALKBH5 locus, by reducing Histone H3 lysine 9 trimethylation (H3K9me3) levels and promoting recruitment of MYB and Pol II. Moreover, ALKBH5 affects mRNA stability of receptor tyrosine kinase AXL in an m6A-dependent way. RNA demethylase ALKBH5 promotes tumorigenesis of t (8; 21) acute myeloid leukemia via Inosine triphosphate pyrophosphatase (ITPA) m6A modification" M6ADIS0046 32402251; 36899424 . M6ACROT03276 REG00006 M6ATAR00118 Histone modification / Methylation EPIREG00047 EPITAR00204 EPITAR00195 Up regulation Histone modification Direct Inhibition m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "Both the univariate and multivariate Cox regression analysis indicated that METTL14 was an independent prognostic factor in CRC. Moreover, KDM5C-mediated demethylation of Histone H3 lysine 36 trimethylation (H3K36me3) in the promoter of METTL14 inhibited METTL14 transcription. METTL14 suppressed Colorectal cancer cell growth, migration, and invasion via the microRNA 375 (MIR375)/YAP1 and miR-375/SP1 pathways." M6ADIS0059 32552762; 31839484 . M6ACROT03277 REG00006 M6ATAR00152 Histone modification / Methylation EPIREG00047 EPITAR00204 EPITAR00195 Up regulation Histone modification Direct Inhibition m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "Both the univariate and multivariate Cox regression analysis indicated that METTL14 was an independent prognostic factor in CRC. Moreover, KDM5C-mediated demethylation of Histone H3 lysine 36 trimethylation (H3K36me3) in the promoter of METTL14 inhibited METTL14 transcription. In colorectal cancer, knockdown of METTL14 substantially abolished m6A level of X inactive specific transcript (XIST) and augmented XIST expression. m6A-methylated XIST was recognized by YTHDF2, a m6A reader protein, to mediate the degradation of XIST. " M6ADIS0059 32552762; 32111213 . M6ACROT03278 REG00006 M6ATAR00521 Histone modification / Methylation EPIREG00047 EPITAR00204 EPITAR00195 Down regulation Histone modification Direct Inhibition m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "Both the univariate and multivariate Cox regression analysis indicated that METTL14 was an independent prognostic factor in CRC. Moreover, KDM5C-mediated demethylation of Histone H3 lysine 36 trimethylation (H3K36me3) in the promoter of METTL14 inhibited METTL14 transcription. In colorectal cancer, Mettl3- or METTL14-deficient tumors increased cytotoxic tumor-infiltrating CD8+ T cells and elevated secretion of Interferon gamma (IFN-gamma), Cxcl9, and Cxcl10 in tumor microenvironment in vivo. Mechanistically, Mettl3 or METTL14 loss promoted IFN-gamma-Stat1-Irf1 signaling through stabilizing the Stat1 and Irf1 mRNA via Ythdf2." M6ADIS0059 32552762; 32964498 . M6ACROT03279 REG00006 M6ATAR00522 Histone modification / Methylation EPIREG00047 EPITAR00204 EPITAR00195 Down regulation Histone modification Direct Inhibition m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "Both the univariate and multivariate Cox regression analysis indicated that METTL14 was an independent prognostic factor in CRC. Moreover, KDM5C-mediated demethylation of Histone H3 lysine 36 trimethylation (H3K36me3) in the promoter of METTL14 inhibited METTL14 transcription. In colorectal cancer, Mettl3- or METTL14-deficient tumors increased cytotoxic tumor-infiltrating CD8+ T cells and elevated secretion of IFN-gamma, C-X-C motif chemokine 9 (Cxcl9), and Cxcl10 in tumor microenvironment in vivo. Mechanistically, Mettl3 or METTL14 loss promoted IFN-gamma-Stat1-Irf1 signaling through stabilizing the Stat1 and Irf1 mRNA via Ythdf2." M6ADIS0059 32552762; 32964498 . M6ACROT03280 REG00006 M6ATAR00523 Histone modification / Methylation EPIREG00047 EPITAR00204 EPITAR00195 Down regulation Histone modification Direct Inhibition m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "Both the univariate and multivariate Cox regression analysis indicated that METTL14 was an independent prognostic factor in CRC. Moreover, KDM5C-mediated demethylation of Histone H3 lysine 36 trimethylation (H3K36me3) in the promoter of METTL14 inhibited METTL14 transcription. In colorectal cancer, Mettl3- or METTL14-deficient tumors increased cytotoxic tumor-infiltrating CD8+ T cells and elevated secretion of IFN-gamma, Cxcl9, and C-X-C motif chemokine 10 (Cxcl10) in tumor microenvironment in vivo. Mechanistically, Mettl3 or METTL14 loss promoted IFN-gamma-Stat1-Irf1 signaling through stabilizing the Stat1 and Irf1 mRNA via Ythdf2." M6ADIS0059 32552762; 32964498 . M6ACROT03281 REG00006 M6ATAR00524 Histone modification / Methylation EPIREG00047 EPITAR00204 EPITAR00195 Down regulation Histone modification Direct Inhibition m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "Both the univariate and multivariate Cox regression analysis indicated that METTL14 was an independent prognostic factor in CRC. Moreover, KDM5C-mediated demethylation of Histone H3 lysine 36 trimethylation (H3K36me3) in the promoter of METTL14 inhibited METTL14 transcription. In colorectal cancer, Mettl3- or METTL14-deficient tumors increased cytotoxic tumor-infiltrating CD8+ T cells and elevated secretion of IFN-gamma, Cxcl9, and Cxcl10 in tumor microenvironment in vivo. Mechanistically, Mettl3 or METTL14 loss promoted IFN-gamma-Stat1-Irf1 signaling through stabilizing the Transcription factor ISGF-3 components p91/p84 (Stat1) and Irf1 mRNA via Ythdf2." M6ADIS0059 32552762; 32964498 . M6ACROT03282 REG00006 M6ATAR00525 Histone modification / Methylation EPIREG00047 EPITAR00204 EPITAR00195 Down regulation Histone modification Direct Inhibition m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "Both the univariate and multivariate Cox regression analysis indicated that METTL14 was an independent prognostic factor in CRC. Moreover, KDM5C-mediated demethylation of Histone H3 lysine 36 trimethylation (H3K36me3) in the promoter of METTL14 inhibited METTL14 transcription. In colorectal cancer, Mettl3- or METTL14-deficient tumors increased cytotoxic tumor-infiltrating CD8+ T cells and elevated secretion of IFN-gamma, Cxcl9, and Cxcl10 in tumor microenvironment in vivo. Mechanistically, Mettl3 or METTL14 loss promoted IFN-gamma-Stat1-Irf1 signaling through stabilizing the Stat1 and Interferon regulatory factor 1 (Irf1) mRNA via Ythdf2." M6ADIS0059 32552762; 32964498 . M6ACROT03283 REG00006 M6ATAR00527 Histone modification / Methylation EPIREG00047 EPITAR00204 EPITAR00195 Up regulation Histone modification Direct Inhibition m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "Both the univariate and multivariate Cox regression analysis indicated that METTL14 was an independent prognostic factor in CRC. Moreover, KDM5C-mediated demethylation of Histone H3 lysine 36 trimethylation (H3K36me3) in the promoter of METTL14 inhibited METTL14 transcription. Knockdown of METTL14 significantly enhanced Arrestin domain-containing protein 4 (ARRDC4) mRNA stability relying on the ""reader"" protein YHTDF2 dependent manner in colorectal cancer." M6ADIS0059 32552762; 34916487 . M6ACROT03284 REG00006 M6ATAR00310 Histone modification / Methylation EPIREG00047 EPITAR00204 EPITAR00195 Up regulation Histone modification Direct Inhibition m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "Both the univariate and multivariate Cox regression analysis indicated that METTL14 was an independent prognostic factor in CRC. Moreover, KDM5C-mediated demethylation of Histone H3 lysine 36 trimethylation (H3K36me3) in the promoter of METTL14 inhibited METTL14 transcription. The expression of METTL14 was downregulated in CRC cells and METTL14 could inhibit the metastasis of CRC cells. MeCP2 could bind to METTL14 to coregulate tumor suppressor Krueppel-like factor 4 (KLF4) expression through changing m6A methylation modification." M6ADIS0059 32552762; 34097350 . M6ACROT03285 REG00006 M6ATAR00836 Histone modification / Methylation EPIREG00047 EPITAR00204 EPITAR00195 Up regulation Histone modification Direct Inhibition m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "Both the univariate and multivariate Cox regression analysis indicated that METTL14 was an independent prognostic factor in CRC. Moreover, KDM5C-mediated demethylation of Histone H3 lysine 36 trimethylation (H3K36me3) in the promoter of METTL14 inhibited METTL14 transcription. Tl increased the level of aberrant N6-methyladenosine (m6A) modification of Polyamine-transporting ATPase 13A3 (ATP13A3) via the METLL3/METTL14/ALKBH5-ATP13A4 axis to promote colorectal tumorigenesis." M6ADIS0059 32552762; 36745568 . M6ACROT03286 REG00006 M6ATAR00993 Histone modification / Methylation EPIREG00047 EPITAR00204 EPITAR00195 Up regulation Histone modification Direct Inhibition m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "Both the univariate and multivariate Cox regression analysis indicated that METTL14 was an independent prognostic factor in CRC. Moreover, KDM5C-mediated demethylation of Histone H3 lysine 36 trimethylation (H3K36me3) in the promoter of METTL14 inhibited METTL14 transcription. m6A mRNA methylation initiated by METTL14 inhibits pri-miR-17 mRNA decay via reducing the recognition of YTHDC2 to the ""GGACC"" binding site. The METTL14/miR-17-5p/MFN2 signaling axis may play a critical role in 5-FU chemoresistance in CRC." M6ADIS0059 32552762; 36810285 M6ADRUG0005 M6ACROT03287 REG00006 M6ATAR00994 Histone modification / Methylation EPIREG00047 EPITAR00204 EPITAR00195 . Histone modification Direct Inhibition m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "Both the univariate and multivariate Cox regression analysis indicated that METTL14 was an independent prognostic factor in CRC. Moreover, KDM5C-mediated demethylation of Histone H3 lysine 36 trimethylation (H3K36me3) in the promoter of METTL14 inhibited METTL14 transcription. The rs11245997 A allele facilitated BET1-like protein (BET1L) expression by disrupting miR-140-3p binding. It also reduced BET1L m6A modification, which upregulated BET1L expression levels through a mechanism mediated by the m6A methyltransferases (METTL14 and WTAP) and the m6A demethylase ALKBH5." M6ADIS0059 32552762; 37115853 . M6ACROT03288 REG00006 M6ATAR01012 Histone modification / Methylation EPIREG00047 EPITAR00204 EPITAR00195 . Histone modification Direct Inhibition m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "Both the univariate and multivariate Cox regression analysis indicated that METTL14 was an independent prognostic factor in CRC. Moreover, KDM5C-mediated demethylation of Histone H3 lysine 36 trimethylation (H3K36me3) in the promoter of METTL14 inhibited METTL14 transcription. METTL14/ALKBH5/IGF2BPs combine to modulate JmjC domain-containing protein 8 (JMJD8) stability in an m6A-dependent manner, which increases glycolysis and accelerates the development of CRC by enhancing the enzymatic activity of PKM2." M6ADIS0059 32552762; 37310898 . M6ACROT03289 REG00008 M6ATAR00152 Histone modification / Methylation EPIREG00047 EPITAR00204 EPITAR00195 Up regulation Histone modification Indirect Inhibition m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "Both the univariate and multivariate Cox regression analysis indicated that METTL14 was an independent prognostic factor in CRC. Moreover, KDM5C-mediated demethylation of Histone H3 lysine 36 trimethylation (H3K36me3) in the promoter of METTL14 inhibited METTL14 transcription. In colorectal cancer, knockdown of METTL14 substantially abolished m6A level of X inactive specific transcript (XIST) and augmented XIST expression. m6A-methylated XIST was recognized by YTHDF2, a m6A reader protein, to mediate the degradation of XIST. " M6ADIS0059 32552762; 32111213 . M6ACROT03290 REG00008 M6ATAR00524 Histone modification / Methylation EPIREG00047 EPITAR00204 EPITAR00195 Down regulation Histone modification Indirect Inhibition m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "Both the univariate and multivariate Cox regression analysis indicated that METTL14 was an independent prognostic factor in CRC. Moreover, KDM5C-mediated demethylation of Histone H3 lysine 36 trimethylation (H3K36me3) in the promoter of METTL14 inhibited METTL14 transcription. In colorectal cancer, Mettl3- or METTL14-deficient tumors increased cytotoxic tumor-infiltrating CD8+ T cells and elevated secretion of IFN-gamma, Cxcl9, and Cxcl10 in tumor microenvironment in vivo. Mechanistically, Mettl3 or METTL14 loss promoted IFN-gamma-Stat1-Irf1 signaling through stabilizing the Transcription factor ISGF-3 components p91/p84 (Stat1) and Irf1 mRNA via YHTDF2." M6ADIS0059 32552762; 32964498 . M6ACROT03291 REG00008 M6ATAR00525 Histone modification / Methylation EPIREG00047 EPITAR00204 EPITAR00195 Down regulation Histone modification Indirect Inhibition m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "Both the univariate and multivariate Cox regression analysis indicated that METTL14 was an independent prognostic factor in CRC. Moreover, KDM5C-mediated demethylation of Histone H3 lysine 36 trimethylation (H3K36me3) in the promoter of METTL14 inhibited METTL14 transcription. In colorectal cancer, Mettl3- or METTL14-deficient tumors increased cytotoxic tumor-infiltrating CD8+ T cells and elevated secretion of IFN-gamma, Cxcl9, and Cxcl10 in tumor microenvironment in vivo. Mechanistically, Mettl3 or METTL14 loss promoted IFN-gamma-Stat1-Irf1 signaling through stabilizing the Stat1 and Interferon regulatory factor 1 (Irf1) mRNA via YHTDF2." M6ADIS0059 32552762; 32964498 . M6ACROT03292 REG00008 M6ATAR00527 Histone modification / Methylation EPIREG00047 EPITAR00204 EPITAR00195 Up regulation Histone modification Indirect Inhibition m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "Both the univariate and multivariate Cox regression analysis indicated that METTL14 was an independent prognostic factor in CRC. Moreover, KDM5C-mediated demethylation of Histone H3 lysine 36 trimethylation (H3K36me3) in the promoter of METTL14 inhibited METTL14 transcription. Knockdown of METTL14 significantly enhanced Arrestin domain-containing protein 4 (ARRDC4) mRNA stability relying on the ""reader"" protein YHTDF2 dependent manner in colorectal cancer." M6ADIS0059 32552762; 34916487 . M6ACROT03293 REG00007 M6ATAR00404 Histone modification / Acetylation EPIREG00036 EPITAR00203 EPITAR00027 Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "METTL3 is required to maintain the features of GBM stem cells. When combined with TMZ, METTL3 silencing suppressed orthotopic TMZ-resistant xenograft growth in a cooperative manner. Mechanistically, TMZ induced a SOX4-mediated increase in chromatin accessibility at the METTL3 locus by promoting Histone H3 lysine 27 acetylation (H3K27ac) levels and recruiting RNA polymerase II. Moreover, METTL3 depletion affected the deposition of m6A on histone modification-related gene transcripts, such as EZH2, leading to nonsense-mediated mRNA decay. GBM tumors have elevated levels of METTL3 transcripts and silencing METTL3 in U87/TIC inhibited tumor growth in an intracranial orthotopic mouse model with prolonged mice survival. The exogenous overexpression of 3'UTR-less Transcription factor SOX-2 (SOX2) significantly alleviated the inhibition of neurosphere formation observed in METTL3 silenced GSCs. " M6ADIS0001 34586728; 28991227 . M6ACROT03294 REG00007 M6ATAR00416 Histone modification / Acetylation EPIREG00036 EPITAR00203 EPITAR00027 Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "METTL3 is required to maintain the features of GBM stem cells. When combined with TMZ, METTL3 silencing suppressed orthotopic TMZ-resistant xenograft growth in a cooperative manner. Mechanistically, TMZ induced a SOX4-mediated increase in chromatin accessibility at the METTL3 locus by promoting Histone H3 lysine 27 acetylation (H3K27ac) levels and recruiting RNA polymerase II. Moreover, METTL3 depletion affected the deposition of m6A on histone modification-related gene transcripts, such as EZH2, leading to nonsense-mediated mRNA decay. Silencing METTL3 or overexpressing dominant-negative mutant METTL3 suppressed the growth and self-renewal of Glioblastoma cells. Integrated transcriptome and MeRIP-seq analyses revealed that downregulating the expression of METTL3 decreased m6A modification levels of Serine/arginine-rich splicing factor 3 (SRSF3), which led to YTHDC1-dependent NMD of SRSF transcripts and decreased SRSF protein expression. " M6ADIS0001 34586728; 31530567 . M6ACROT03295 REG00007 M6ATAR00417 Histone modification / Acetylation EPIREG00036 EPITAR00203 EPITAR00027 Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "METTL3 is required to maintain the features of GBM stem cells. When combined with TMZ, METTL3 silencing suppressed orthotopic TMZ-resistant xenograft growth in a cooperative manner. Mechanistically, TMZ induced a SOX4-mediated increase in chromatin accessibility at the METTL3 locus by promoting Histone H3 lysine 27 acetylation (H3K27ac) levels and recruiting RNA polymerase II. Moreover, METTL3 depletion affected the deposition of m6A on histone modification-related gene transcripts, such as EZH2, leading to nonsense-mediated mRNA decay. Silencing METTL3 or overexpressing dominant-negative mutant METTL3 suppressed the growth and self-renewal of Glioblastoma cells. Integrated transcriptome and MeRIP-seq analyses revealed that downregulating the expression of METTL3 decreased m6A modification levels of Serine/arginine-rich splicing factor 6 (SRSF6), which led to YTHDC1-dependent NMD of SRSF transcripts and decreased SRSF protein expression. " M6ADIS0001 34586728; 31530567 . M6ACROT03296 REG00007 M6ATAR00415 Histone modification / Acetylation EPIREG00036 EPITAR00203 EPITAR00027 Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "METTL3 is required to maintain the features of GBM stem cells. When combined with TMZ, METTL3 silencing suppressed orthotopic TMZ-resistant xenograft growth in a cooperative manner. Mechanistically, TMZ induced a SOX4-mediated increase in chromatin accessibility at the METTL3 locus by promoting Histone H3 lysine 27 acetylation (H3K27ac) levels and recruiting RNA polymerase II. Moreover, METTL3 depletion affected the deposition of m6A on histone modification-related gene transcripts, such as EZH2, leading to nonsense-mediated mRNA decay. Silencing METTL3 or overexpressing dominant-negative mutant METTL3 suppressed the growth and self-renewal of Glioblastoma cells. Integrated transcriptome and MeRIP-seq analyses revealed that downregulating the expression of METTL3 decreased m6A modification levels of Serine/arginine-rich splicing factor 11 (SRSF11), which led to YTHDC1-dependent NMD of SRSF transcripts and decreased SRSF protein expression. " M6ADIS0001 34586728; 31530567 . M6ACROT03297 REG00007 M6ATAR00326 Histone modification / Acetylation EPIREG00036 EPITAR00203 EPITAR00027 Down regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "METTL3 is required to maintain the features of GBM stem cells. When combined with TMZ, METTL3 silencing suppressed orthotopic TMZ-resistant xenograft growth in a cooperative manner. Mechanistically, TMZ induced a SOX4-mediated increase in chromatin accessibility at the METTL3 locus by promoting Histone H3 lysine 27 acetylation (H3K27ac) levels and recruiting RNA polymerase II. Moreover, METTL3 depletion affected the deposition of m6A on histone modification-related gene transcripts, such as EZH2, leading to nonsense-mediated mRNA decay. Two critical DNA repair genes (Methylated-DNA--protein-cysteine methyltransferase (MGMT) and APNG) were m6A-modified by METTL3, whereas inhibited by METTL3 silencing or DAA-mediated total methylation inhibition, which is crucial for METTL3-improved temozolomide resistance in glioblastoma cells." M6ADIS0001 34586728; 34336690 M6ADRUG0010 M6ACROT03298 REG00007 M6ATAR00158 Histone modification / Acetylation EPIREG00036 EPITAR00203 EPITAR00027 Down regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "METTL3 is required to maintain the features of GBM stem cells. When combined with TMZ, METTL3 silencing suppressed orthotopic TMZ-resistant xenograft growth in a cooperative manner. Mechanistically, TMZ induced a SOX4-mediated increase in chromatin accessibility at the METTL3 locus by promoting Histone H3 lysine 27 acetylation (H3K27ac) levels and recruiting RNA polymerase II. Moreover, METTL3 depletion affected the deposition of m6A on histone modification-related gene transcripts, such as EZH2, leading to nonsense-mediated mRNA decay. Two critical DNA repair genes (MGMT and DNA-3-methyladenine glycosylase (ANPG/MPG)) were m6A-modified by METTL3, whereas inhibited by METTL3 silencing or DAA-mediated total methylation inhibition, which is crucial for METTL3-improved temozolomide resistance in glioblastoma cells." M6ADIS0001 34586728; 34336690 M6ADRUG0010 M6ACROT03299 REG00007 M6ATAR00171 Histone modification / Acetylation EPIREG00036 EPITAR00203 EPITAR00027 Down regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "METTL3 is required to maintain the features of GBM stem cells. When combined with TMZ, METTL3 silencing suppressed orthotopic TMZ-resistant xenograft growth in a cooperative manner. Mechanistically, TMZ induced a SOX4-mediated increase in chromatin accessibility at the METTL3 locus by promoting Histone H3 lysine 27 acetylation (H3K27ac) levels and recruiting RNA polymerase II. Moreover, METTL3 depletion affected the deposition of m6A on histone modification-related gene transcripts, such as EZH2, leading to nonsense-mediated mRNA decay. Knockdown of METTL3 or METTL14 induced changes in mRNA m6A enrichment and altered mRNA expression of genes (e.g., Meltrin-beta (ADAM19)) with critical biological functions in GSCs. Treatment with MA2, a chemical inhibitor of FTO, dramatically suppressed GSC-induced tumorigenesis and prolonged lifespan in GSC-grafted animals." M6ADIS0001 34586728; 28297667 M6ADRUG0076 M6ACROT03300 REG00007 M6ATAR00536 Histone modification / Acetylation EPIREG00036 EPITAR00203 EPITAR00027 Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "METTL3 is required to maintain the features of GBM stem cells. When combined with TMZ, METTL3 silencing suppressed orthotopic TMZ-resistant xenograft growth in a cooperative manner. Mechanistically, TMZ induced a SOX4-mediated increase in chromatin accessibility at the METTL3 locus by promoting Histone H3 lysine 27 acetylation (H3K27ac) levels and recruiting RNA polymerase II. Moreover, METTL3 depletion affected the deposition of m6A on histone modification-related gene transcripts, such as EZH2, leading to nonsense-mediated mRNA decay. METTL3, upregulated in glioblastoma, methylates Interferon-inducible protein 4 (ADAR1) mRNA and increases its protein level leading to a pro-tumorigenic mechanism connecting METTL3, YTHDF1, and ADAR1." M6ADIS0001 34586728; 33509238 . M6ACROT03301 REG00007 M6ATAR00326 Histone modification / Acetylation EPIREG00036 EPITAR00203 EPITAR00027 Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "METTL3 is required to maintain the features of GBM stem cells. When combined with TMZ, METTL3 silencing suppressed orthotopic TMZ-resistant xenograft growth in a cooperative manner. Mechanistically, TMZ induced a SOX4-mediated increase in chromatin accessibility at the METTL3 locus by promoting Histone H3 lysine 27 acetylation (H3K27ac) levels and recruiting RNA polymerase II. Moreover, METTL3 depletion affected the deposition of m6A on histone modification-related gene transcripts, such as EZH2, leading to nonsense-mediated mRNA decay. METTL3 knockdown promotes temozolomide sensitivity of glioma stem cells via decreasing Methylated-DNA--protein-cysteine methyltransferase (MGMT) and APNG mRNA stability" M6ADIS0001 34586728; 36683086 . M6ACROT03302 REG00007 M6ATAR00158 Histone modification / Acetylation EPIREG00036 EPITAR00203 EPITAR00027 Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "METTL3 is required to maintain the features of GBM stem cells. When combined with TMZ, METTL3 silencing suppressed orthotopic TMZ-resistant xenograft growth in a cooperative manner. Mechanistically, TMZ induced a SOX4-mediated increase in chromatin accessibility at the METTL3 locus by promoting Histone H3 lysine 27 acetylation (H3K27ac) levels and recruiting RNA polymerase II. Moreover, METTL3 depletion affected the deposition of m6A on histone modification-related gene transcripts, such as EZH2, leading to nonsense-mediated mRNA decay. METTL3 knockdown promotes temozolomide sensitivity of glioma stem cells via decreasing MGMT and DNA-3-methyladenine glycosylase (ANPG/MPG) mRNA stability" M6ADIS0001 34586728; 36683086 . M6ACROT03303 REG00007 M6ATAR01485 Histone modification / Acetylation EPIREG00036 EPITAR00203 EPITAR00027 Down regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "METTL3 is required to maintain the features of GBM stem cells. When combined with TMZ, METTL3 silencing suppressed orthotopic TMZ-resistant xenograft growth in a cooperative manner. Mechanistically, TMZ induced a SOX4-mediated increase in chromatin accessibility at the METTL3 locus by promoting Histone H3 lysine 27 acetylation (H3K27ac) levels and recruiting RNA polymerase II. Moreover, METTL3 depletion affected the deposition of m6A on histone modification-related gene transcripts, such as EZH2, leading to nonsense-mediated mRNA decay. Specifically, PDGF-PDGFRB signaling upregulates the expression of the m6A methyltransferase METTL3, which then decorates the mitophagy regulator Optineurin (OPTN) mRNA with m6A, thereby promoting OPTN mRNA degradation." M6ADIS0001 34586728; 35980802 . M6ACROT03304 REG00007 M6ATAR01409 Histone modification / Acetylation EPIREG00036 EPITAR00203 EPITAR00027 . Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "METTL3 is required to maintain the features of GBM stem cells. When combined with TMZ, METTL3 silencing suppressed orthotopic TMZ-resistant xenograft growth in a cooperative manner. Mechanistically, TMZ induced a SOX4-mediated increase in chromatin accessibility at the METTL3 locus by promoting Histone H3 lysine 27 acetylation (H3K27ac) levels and recruiting RNA polymerase II. Moreover, METTL3 depletion affected the deposition of m6A on histone modification-related gene transcripts, such as EZH2, leading to nonsense-mediated mRNA decay. mRNA levels of Aryl hydrocarbon receptor (AHR) and SRF were stabilized by decreased METTL3 and YTHDF2. YKL-40 and Kyn secreted from tumor cells and infiltrating M2 macrophages cooperated to enhance tumor cell migration and inhibit CTL immunity. In xenografts, tumors expressing YKL-40 displayed the elevated KP metabolism and macrophage infiltration, but decreased CTLs. " M6ADIS0001 34586728; 38332508 M6ADRUG0111 M6ACROT03305 REG00007 M6ATAR00461 Histone modification / Acetylation EPIREG00036 EPITAR00203 EPITAR00027 . Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "METTL3 is required to maintain the features of GBM stem cells. When combined with TMZ, METTL3 silencing suppressed orthotopic TMZ-resistant xenograft growth in a cooperative manner. Mechanistically, TMZ induced a SOX4-mediated increase in chromatin accessibility at the METTL3 locus by promoting Histone H3 lysine 27 acetylation (H3K27ac) levels and recruiting RNA polymerase II. Moreover, METTL3 depletion affected the deposition of m6A on histone modification-related gene transcripts, such as EZH2, leading to nonsense-mediated mRNA decay. mRNA levels of AhR and Serum response factor (SRF) were stabilized by decreased METTL3 and YTHDF2. YKL-40 and Kyn secreted from tumor cells and infiltrating M2 macrophages cooperated to enhance tumor cell migration and inhibit CTL immunity. In xenografts, tumors expressing YKL-40 displayed the elevated KP metabolism and macrophage infiltration, but decreased CTLs. " M6ADIS0001 34586728; 38332508 M6ADRUG0111 M6ACROT03306 REG00007 M6ATAR00152 Histone modification / Lactylation . EPITAR00208 EPITAR00027 Up regulation Histone modification Direct Enhancement m6A Histone modification directly impacts m6A modification through modulating the level of m6A regulator "LDHA knockdown-mediated inhibition of endogenous Histone H3 lysine 18 lactylation (H3K18la) suppressed osteogenic differentiation, a phenotype that was rescued by METTL3 overexpression. In conclusion, this study elucidates that histone lactylation-mediated upregulation of METTL3 promotes OLF progression through IGF2BP1-dependent m6A methylation of BMP2, providing novel insights into potential therapeutic strategies for OLF management. METTL3 regulates ossification of the posterior longitudinal ligament via the lncRNA X inactive specific transcript (XIST)/miR-302a-3p/USP8 axis." M6ADIS0113 40133819; 33748113 . M6ACROT03307 REG00006 M6ATAR00955 Histone modification / Methylation EPIREG00053 EPITAR00204 EPITAR00195 Up regulation Histone modification Direct Inhibition m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "KDM5B downregulated METTL14 expression at the transcriptional level in a Histone H3 lysine 4 trimethylation (H3K4me3)-dependent manner, while METTL14 modulated LINC02747 expression via m6A modification. Our results demonstrate a synergy of multiple mechanisms in regulating the malignant phenotype of NSCLC, revealing the complex regulation involved in the occurrence and development of cancer.In brief, METTL14 promoted NSCLC development by increasing m6A methylation of Zinc finger protein PLAGL2 (PLAGL2) to activate beta-catenin signaling. " M6ADIS0007 38888105; 36873735 . M6ACROT03308 REG00006 M6ATAR01480 Histone modification / Methylation EPIREG00053 EPITAR00204 EPITAR00195 Up regulation Histone modification Direct Inhibition m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "KDM5B downregulated METTL14 expression at the transcriptional level in a Histone H3 lysine 4 trimethylation (H3K4me3)-dependent manner, while METTL14 modulated LINC02747 expression via m6A modification. Our results demonstrate a synergy of multiple mechanisms in regulating the malignant phenotype of NSCLC, revealing the complex regulation involved in the occurrence and development of cancer.RNA m6A methyltransferase METTL14 promotes the procession of non-small cell lung cancer by targeted Macrophage colony-stimulating factor 1 receptor (CSF1R)" M6ADIS0007 38888105; 36448247 . M6ACROT03309 REG00006 M6ATAR00124 Histone modification / Methylation EPIREG00053 EPITAR00204 EPITAR00195 Up regulation Histone modification Direct Inhibition m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "KDM5B downregulated METTL14 expression at the transcriptional level in a Histone H3 lysine 4 trimethylation (H3K4me3)-dependent manner, while METTL14 modulated LINC02747 expression via m6A modification. Our results demonstrate a synergy of multiple mechanisms in regulating the malignant phenotype of NSCLC, revealing the complex regulation involved in the occurrence and development of cancer.METTL14 drives growth and metastasis of non-small cell lung cancer by regulating microRNA 93 (MIR93) maturation and TXNIP expression" M6ADIS0007 38888105; 37594665 . M6ACROT03310 REG00009 M6ATAR00628 Histone modification / Acetylation EPIREG00034 EPITAR00203 EPITAR00269 Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "WTAP upregulated in NPC was fine-tuned by CREBBP-mediated Histone H3 lysine 27 acetylation (H3K27ac). WTAP-mediated m6A modification of lncRNA DIAPH1-AS1 enhances its stability to facilitate nasopharyngeal carcinoma growth and metastasis.WTAP-mediated m6A modification of DIAPH1 antisense RNA 1 (DIAPH1-AS1) enhanced its stability relying on the m6A reader IGF2BP2-dependent pathway. Furthermore, DIAPH1-AS1 acted as a molecular adaptor that promoted MTDH-LIM and SH3 domain protein 1 (LASP1) complex formation and upregulated LASP1 expression, ultimately facilitating NPC growth and metastasis." M6ADIS0054 34999731 . M6ACROT03311 REG00007 M6ATAR00623 Histone modification / Methylation EPIREG00039 EPITAR00204 EPITAR00027 Down regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator KMT2A induced rapid Histone H3 lysine 4 trimethylation (H3K4me3) of the promoter of the methyltransferase-like 3 gene (METTL3) and resulted in its overexpression. METTL3 overexpression evokes N6-methyladenosine (m6A)-dependent miR-503 biogenesis in endothelial cells. METTL3 deficiency contributes to heart regeneration after MI via METTL3-pri-miR-143-(miR-143)-Yap/Ctnnd1 axis. M6ADIS0097 35452193; 34428587 . M6ACROT03312 REG00007 M6ATAR00841 Histone modification / Methylation EPIREG00039 EPITAR00204 EPITAR00027 Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator KMT2A induced rapid Histone H3 lysine 4 trimethylation (H3K4me3) of the promoter of the methyltransferase-like 3 gene (METTL3) and resulted in its overexpression. METTL3 overexpression evokes N6-methyladenosine (m6A)-dependent miR-503 biogenesis in endothelial cells. METTL3 led to enhanced m6A levels of Tenascin (TNC) mRNA and promoted TNC mRNA stability. M6ADIS0097 35452193; 36980863 . M6ACROT03313 REG00007 M6ATAR00596 Histone modification / Methylation EPIREG00039 EPITAR00204 EPITAR00027 Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "KMT2A induced rapid Histone H3 lysine 4 trimethylation (H3K4me3) of the promoter of the methyltransferase-like 3 gene (METTL3) and resulted in its overexpression. METTL3 overexpression evokes N6-methyladenosine (m6A)-dependent miR-503 biogenesis in endothelial cells. METTL3-mediated m6A modification promotes sympathetic hyperactivity through TNF receptor-associated factor 6 (TRAF6)/ECSIT pathway and mitochondrial oxidative stress in the PVN, thereby leading to ventricular arrhythmias post-MI." M6ADIS0097 35452193; 37898386 . M6ACROT03314 REG00007 M6ATAR01060 Histone modification / Methylation EPIREG00039 EPITAR00204 EPITAR00027 Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator KMT2A induced rapid Histone H3 lysine 4 trimethylation (H3K4me3) of the promoter of the methyltransferase-like 3 gene (METTL3) and resulted in its overexpression. METTL3 overexpression evokes N6-methyladenosine (m6A)-dependent miR-503 biogenesis in endothelial cells. Programmed Release METTL3-14 Inhibitor Microneedle Protects Myocardial Function by Reducing Dynamin-1-like protein (DRP1) m6A Modification-Mediated Mitochondrial Fission M6ADIS0097 35452193; 37752784 . M6ACROT03315 REG00007 M6ATAR00280 Histone modification / Methylation EPIREG00042 EPITAR00211 EPITAR00109 Down regulation Histone modification Indirect Inhibition m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "JMJD1C increased MIR302A expression through promoting Histone H3 lysine 9 monomethylation (H3K9me1) demethylation at the miR-302a promoter region. miR-302a was identified to target METTL3, which could inhibit SOCS2 expression via m6A modification. m6A regulated cell proliferation by influencing apoptosis of U251 cells through regulating Heat shock protein HSP 90-alpha (HSP90/HSP90AA1) expression. m6A level was decreased in glioma tissue, which was caused by decreased METTL3 and increased FTO levels." M6ADIS0001 34586733; 31639789 . M6ACROT03316 REG00007 M6ATAR00141 Histone modification / Methylation EPIREG00042 EPITAR00211 EPITAR00109 Up regulation Histone modification Indirect Inhibition m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "JMJD1C increased MIR302A expression through promoting Histone H3 lysine 9 monomethylation (H3K9me1) demethylation at the miR-302a promoter region. miR-302a was identified to target METTL3, which could inhibit SOCS2 expression via m6A modification. METTL3 promoted the malignant progression of IDH-wildtype gliomas and revealed important insight into the upstream regulatory mechanism of Metastasis associated lung adenocarcinoma transcript 1 (MALAT1) and NF-Kappa-B with a primary focus on m6A modification." M6ADIS0001 34586733; 33933553 . M6ACROT03317 REG00007 M6ATAR00517 Histone modification / Methylation EPIREG00042 EPITAR00211 EPITAR00109 Up regulation Histone modification Indirect Inhibition m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "JMJD1C increased MIR302A expression through promoting Histone H3 lysine 9 monomethylation (H3K9me1) demethylation at the miR-302a promoter region. miR-302a was identified to target METTL3, which could inhibit SOCS2 expression via m6A modification. METTL3-mediated m6A modification upregulated Circ_DLC1 expression, and circDLC1 promoted CTNNBIP1 transcription by sponging miR-671-5p, thus repressing the malignant proliferation of glioma." M6ADIS0001 34586733; 35474040 . M6ACROT03318 REG00007 M6ATAR00613 Histone modification / Methylation EPIREG00042 EPITAR00211 EPITAR00109 Up regulation Histone modification Indirect Inhibition m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "JMJD1C increased MIR302A expression through promoting Histone H3 lysine 9 monomethylation (H3K9me1) demethylation at the miR-302a promoter region. miR-302a was identified to target METTL3, which could inhibit SOCS2 expression via m6A modification. METTL3-mediated m6A modification upregulated circDLC1 expression, and circDLC1 promoted CTNNBIP1 transcription by sponging hsa-miR-671-5p, thus repressing the malignant proliferation of glioma." M6ADIS0001 34586733; 35474040 . M6ACROT03319 REG00007 M6ATAR00614 Histone modification / Methylation EPIREG00042 EPITAR00211 EPITAR00109 Up regulation Histone modification Indirect Inhibition m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "JMJD1C increased MIR302A expression through promoting Histone H3 lysine 9 monomethylation (H3K9me1) demethylation at the miR-302a promoter region. miR-302a was identified to target METTL3, which could inhibit SOCS2 expression via m6A modification. METTL3-mediated m6A modification upregulated circDLC1 expression, and circDLC1 promoted Beta-catenin-interacting protein 1 (CTNNBIP1) transcription by sponging miR-671-5p, thus repressing the malignant proliferation of glioma." M6ADIS0001 34586733; 35474040 . M6ACROT03320 REG00007 M6ATAR00731 Histone modification / Methylation EPIREG00042 EPITAR00211 EPITAR00109 Down regulation Histone modification Indirect Inhibition m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "JMJD1C increased MIR302A expression through promoting Histone H3 lysine 9 monomethylation (H3K9me1) demethylation at the miR-302a promoter region. miR-302a was identified to target METTL3, which could inhibit SOCS2 expression via m6A modification. YTHDF2 accelerated UBX domain-containing protein 1 (UBXN1) mRNA degradation via METTL3-mediated m6A, which, in turn, promoted NF-Kappa-B activation. YTHDF2 promotes the malignant progression of gliomas and revealed important insight into the upstream regulatory mechanism of NF-Kappa-B activation via UBXN1 with a primary focus on m6A modification." M6ADIS0001 34586733; 34246306 . M6ACROT03321 REG00007 M6ATAR00054 Histone modification / Methylation EPIREG00042 EPITAR00211 EPITAR00109 Up regulation Histone modification Indirect Inhibition m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "JMJD1C increased MIR302A expression through promoting Histone H3 lysine 9 monomethylation (H3K9me1) demethylation at the miR-302a promoter region. miR-302a was identified to target METTL3, which could inhibit SOCS2 expression via m6A modification. YTHDF2 accelerated UBXN1 mRNA degradation via METTL3-mediated m6A, which, in turn, promoted Nuclear factor NF-kappa-B p105 subunit (NF-Kappa-B/NFKB1) activation. YTHDF2 promotes the malignant progression of gliomas and revealed important insight into the upstream regulatory mechanism of NF-Kappa-B activation via UBXN1 with a primary focus on m6A modification." M6ADIS0001 34586733; 34246306 . M6ACROT03322 REG00007 M6ATAR01455 Histone modification / Methylation EPIREG00042 EPITAR00211 EPITAR00109 Up regulation Histone modification Indirect Inhibition m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "JMJD1C increased MIR302A expression through promoting Histone H3 lysine 9 monomethylation (H3K9me1) demethylation at the miR-302a promoter region. miR-302a was identified to target METTL3, which could inhibit SOCS2 expression via m6A modification. that HOXA transcript antisense RNA, myeloid-specific 1 (HOTAIRM1), methyltransferase-like 3 (METTL3), and insulin-like growth factor binding protein 2 (IGFBP2) were upregulated in glioma tissues and cell lines. HOTAIRM1 functions as an oncogene in glioma progression; however, knockdown of HOTAIRM1 significantly reduced cell viability, migration, invasion, and VM formation. Notably, METTL3-dependent m6A modification enhanced HOTAIRM1 mRNA stability, whereas knockdown of METTL3 deficiency significantly suppressed VM in glioma. Moreover, HOTAIRM1 was found to bind IGFBP2, and HOTAIRM1 deficiency blocked glioma progression and VM formation in vivo. Our results indicated that METTL3-dependent m6A-modified HOTAIRM1 promoted VM formation in glioma." M6ADIS0001 34586733; 36086906 . M6ACROT03323 REG00007 M6ATAR00974 Histone modification / Methylation EPIREG00042 EPITAR00211 EPITAR00109 Up regulation Histone modification Indirect Inhibition m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "JMJD1C increased MIR302A expression through promoting Histone H3 lysine 9 monomethylation (H3K9me1) demethylation at the miR-302a promoter region. miR-302a was identified to target METTL3, which could inhibit SOCS2 expression via m6A modification. Methyltransferase MELLT3 upregulated m6A modification of Circ_EPHB4, and YTHDC1 promoted cytoplasmic localization of m6A-modified CircEPHB4. Overexpression of wild-type CircEPHB4 enhanced glioma cells' stemness, metastasis, and proliferation. Cytoplasmic CircEPHB4 increased SOX2 mRNA stability by binding to IGF2BP2, and the effects observed by SOX2 knockdown were reversed by CircEPHB4 in glioma cells." M6ADIS0001 34586733; 37614011 . M6ACROT03324 REG00007 M6ATAR01486 Histone modification / Methylation EPIREG00042 EPITAR00211 EPITAR00109 Up regulation Histone modification Indirect Inhibition m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "JMJD1C increased MIR302A expression through promoting Histone H3 lysine 9 monomethylation (H3K9me1) demethylation at the miR-302a promoter region. miR-302a was identified to target METTL3, which could inhibit SOCS2 expression via m6A modification. Fear stress-induced upregulation of METTL3 and Ferroptosis suppressor protein 1 (AIFM2), increased m6A level of glioma tumor tissues, and inhibited ferroptosis in glioma progression, which were reversed by knockdown of METTL3 and FSP1 in vivo. In addition, we found that when iFSP1 (a ferroptosis inducer by targeting inhibition of FSP1) was introduced to glioma cells" M6ADIS0001 34586733; 36484954 M6ADRUG0141 M6ACROT03325 REG00007 M6ATAR01037 Histone modification / Methylation EPIREG00042 EPITAR00211 EPITAR00109 Up regulation Histone modification Indirect Inhibition m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "JMJD1C increased MIR302A expression through promoting Histone H3 lysine 9 monomethylation (H3K9me1) demethylation at the miR-302a promoter region. miR-302a was identified to target METTL3, which could inhibit SOCS2 expression via m6A modification. Circ TTLL13 Promotes TMZ Resistance in Glioma via Modulating Oxidized low-density lipoprotein receptor 1 (OLR1)-Mediated Activation of the Wnt/beta-Catenin Pathway.circTTLL13 stabilizes OLR1 mRNA via recruiting YTH N6-methyladenosine RNA binding protein 1 (YTHDF1) and promotes m6A methylation of OLR1 pre-mRNA through recruiting methyltransferase-like 3 (METTL3)." M6ADIS0001 34586733; 37427890 M6ADRUG0010 M6ACROT03326 REG00007 M6ATAR01392 Histone modification / Methylation EPIREG00042 EPITAR00211 EPITAR00109 . Histone modification Indirect Inhibition m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "JMJD1C increased MIR302A expression through promoting Histone H3 lysine 9 monomethylation (H3K9me1) demethylation at the miR-302a promoter region. miR-302a was identified to target METTL3, which could inhibit SOCS2 expression via m6A modification. Guanine nucleotide-binding protein G (GNAO1) overexpression downregulated HES1 expression, which reinforced neuronal differentiation. In addition, knockdown of METTL3, a key writer of the N6-methyladenosine (m6A), enhanced GNAO1 mRNA stability. " M6ADIS0001 34586733; 39580518 M6ADRUG0010 M6ACROT03327 REG00008 M6ATAR00486 Histone modification / Methylation EPIREG00055 EPITAR00204 EPITAR00470 Down regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "KDM5A, as a Histone H3 lysine 4 trimethylation (H3K4me3) demethylase, bound to the hsa-miR-495 promoter, which led to inhibition of its transcription and expression. As a target of miR-495, YTHDF2 could inhibit MOB3B expression by recognizing m6A modification of MOB3B mRNA and inducing mRNA degradation. In prostate cancer, METTL14 downregulated Thrombospondin-1 (THBS1) expression in an m6A-dependent manner, which resulted in the recruitment of YTHDF2 to recognize and degrade Thrombospondin 1 (THBS1) mRNA." M6ADIS0068 33087165; 35354789 . M6ACROT03328 REG00008 M6ATAR00175 Histone modification / Methylation EPIREG00055 EPITAR00204 EPITAR00470 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "KDM5A, as a Histone H3 lysine 4 trimethylation (H3K4me3) demethylase, bound to the hsa-miR-495 promoter, which led to inhibition of its transcription and expression. As a target of miR-495, YTHDF2 could inhibit MOB3B expression by recognizing m6A modification of MOB3B mRNA and inducing mRNA degradation. Knock-down of YTHDF2 or METTL3 significantly induced the expression of LHPP and NKX3-1 at both mRNA and protein level with inhibited phosphorylated RAC-alpha serine/threonine-protein kinase (AKT1). YTHDF2 mediates the mRNA degradation of the tumor suppressors LHPP and NKX3-1 in m6A-dependent way to regulate AKT phosphorylation-induced tumor progression in prostate cancer." M6ADIS0068 33087165; 33121495 . M6ACROT03329 REG00008 M6ATAR00624 Histone modification / Methylation EPIREG00055 EPITAR00204 EPITAR00470 Down regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "KDM5A, as a Histone H3 lysine 4 trimethylation (H3K4me3) demethylase, bound to the hsa-miR-495 promoter, which led to inhibition of its transcription and expression. As a target of miR-495, YTHDF2 could inhibit MOB3B expression by recognizing m6A modification of MOB3B mRNA and inducing mRNA degradation. Knock-down of YTHDF2 or METTL3 significantly induced the expression of Phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) and NKX3-1 at both mRNA and protein level with inhibited phosphorylated AKT. YTHDF2 mediates the mRNA degradation of the tumor suppressors LHPP and NKX3-1 in m6A-dependent way to regulate AKT phosphorylation-induced tumor progression in prostate cancer." M6ADIS0068 33087165; 33121495 . M6ACROT03330 REG00008 M6ATAR00625 Histone modification / Methylation EPIREG00055 EPITAR00204 EPITAR00470 Down regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "KDM5A, as a Histone H3 lysine 4 trimethylation (H3K4me3) demethylase, bound to the hsa-miR-495 promoter, which led to inhibition of its transcription and expression. As a target of miR-495, YTHDF2 could inhibit MOB3B expression by recognizing m6A modification of MOB3B mRNA and inducing mRNA degradation. Knock-down of YTHDF2 or METTL3 significantly induced the expression of LHPP and Homeobox protein Nkx-3.1 (NKX3-1) at both mRNA and protein level with inhibited phosphorylated AKT. YTHDF2 mediates the mRNA degradation of the tumor suppressors LHPP and NKX3-1 in m6A-dependent way to regulate AKT phosphorylation-induced tumor progression in prostate cancer." M6ADIS0068 33087165; 33121495 . M6ACROT03331 REG00008 M6ATAR00668 Histone modification / Methylation EPIREG00055 EPITAR00204 EPITAR00470 Down regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "KDM5A, as a Histone H3 lysine 4 trimethylation (H3K4me3) demethylase, bound to the hsa-miR-495 promoter, which led to inhibition of its transcription and expression. As a target of miR-495, YTHDF2 could inhibit MOB3B expression by recognizing m6A modification of MOB3B mRNA and inducing mRNA degradation. m6A modification levels were markedly upregulated in human PCa tissues due to increased expression of METTL3. METTL3 mediates m6A modification of Ubiquitin carboxyl-terminal hydrolase 4 (USP4) mRNA at A2696, and m6A reader protein YTHDF2 binds to and induces degradation of USP4 mRNA by recruiting RNA-binding protein HNRNPD to the mRNA. Decrease of USP4 fails to remove the ubiquitin group from ELAVL1 protein, resulting in a reduction of ELAVL1 protein. Lastly, downregulation of ELAVL1 in turn increases ARHGDIA expression, promoting migration and invasion of PCa cells." M6ADIS0068 33087165; 34335955 . M6ACROT03332 REG00008 M6ATAR00241 Histone modification / Methylation EPIREG00055 EPITAR00204 EPITAR00470 Down regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "KDM5A, as a Histone H3 lysine 4 trimethylation (H3K4me3) demethylase, bound to the hsa-miR-495 promoter, which led to inhibition of its transcription and expression. As a target of miR-495, YTHDF2 could inhibit MOB3B expression by recognizing m6A modification of MOB3B mRNA and inducing mRNA degradation. m6A modification levels were markedly upregulated in human PCa tissues due to increased expression of METTL3. METTL3 mediates m6A modification of USP4 mRNA at A2696, and m6A reader protein YTHDF2 binds to and induces degradation of USP4 mRNA by recruiting RNA-binding protein HNRNPD to the mRNA. Decrease of USP4 fails to remove the ubiquitin group from ELAV-like protein 1 (HuR/ELAVL1) protein, resulting in a reduction of ELAVL1 protein. Lastly, downregulation of ELAVL1 in turn increases ARHGDIA expression, promoting migration and invasion of PCa cells." M6ADIS0068 33087165; 34335955 . M6ACROT03333 REG00008 M6ATAR00152 Histone modification / Lactylation EPIREG00035 EPITAR00208 EPITAR00232 Down regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "Histone lactylation activates the transcription of YTHDF2 through p300-mediated Histone H3 lysine 18 lactylation (H3K18la) modification. In colorectal cancer, knockdown of METTL14 substantially abolished m6A level of X inactive specific transcript (XIST) and augmented XIST expression. m6A-methylated XIST was recognized by YTHDF2, a m6A reader protein, to mediate the degradation of XIST. " M6ADIS0059 39269733; 32111213 . M6ACROT03334 REG00008 M6ATAR00185 Histone modification / Lactylation EPIREG00035 EPITAR00208 EPITAR00232 Down regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "Histone lactylation activates the transcription of YTHDF2 through p300-mediated Histone H3 lysine 18 lactylation (H3K18la) modification. In colorectal cancer, Glutaminolysis inhibition upregulated ATF4 expression in an m6A-dependent manner to activate pro-survival autophagy through transcriptional activation of the mTOR inhibitor DDIT4. Determined the relationship between FTO alpha-ketoglutarate dependent dioxygenase (FTO), YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), and ATF4. Cyclic AMP-dependent transcription factor ATF-4 (ATF4) transcriptionally upregulated DDIT4 to suppress mTOR, which induced pro-survival autophagy during glutaminolysis inhibition." M6ADIS0059 39269733; 34373753 M6ADRUG0044 M6ACROT03335 REG00008 M6ATAR00185 Histone modification / Lactylation EPIREG00035 EPITAR00208 EPITAR00232 Down regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "Histone lactylation activates the transcription of YTHDF2 through p300-mediated Histone H3 lysine 18 lactylation (H3K18la) modification. In colorectal cancer, Glutaminolysis inhibition upregulated ATF4 expression in an m6A-dependent manner to activate pro-survival autophagy through transcriptional activation of the mTOR inhibitor DDIT4. Determined the relationship between FTO alpha-ketoglutarate dependent dioxygenase (FTO), YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), and ATF4. ATF4 transcriptionally upregulated DDIT4 to suppress Cyclic AMP-dependent transcription factor ATF-4 (ATF4), which induced pro-survival autophagy during glutaminolysis inhibition." M6ADIS0059 39269733; 34373753 M6ADRUG0082 M6ACROT03336 REG00008 M6ATAR00185 Histone modification / Lactylation EPIREG00035 EPITAR00208 EPITAR00232 Down regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "Histone lactylation activates the transcription of YTHDF2 through p300-mediated Histone H3 lysine 18 lactylation (H3K18la) modification. In colorectal cancer, Glutaminolysis inhibition upregulated ATF4 expression in an m6A-dependent manner to activate pro-survival autophagy through transcriptional activation of the mTOR inhibitor DDIT4. Determined the relationship between FTO alpha-ketoglutarate dependent dioxygenase (FTO), YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), and ATF4. ATF4 transcriptionally upregulated DDIT4 to suppress Cyclic AMP-dependent transcription factor ATF-4 (ATF4), which induced pro-survival autophagy during glutaminolysis inhibition." M6ADIS0059 39269733; 34373753 M6ADRUG0073 M6ACROT03337 REG00008 M6ATAR00185 Histone modification / Lactylation EPIREG00035 EPITAR00208 EPITAR00232 Down regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "Histone lactylation activates the transcription of YTHDF2 through p300-mediated Histone H3 lysine 18 lactylation (H3K18la) modification. In colorectal cancer, Glutaminolysis inhibition upregulated ATF4 expression in an m6A-dependent manner to activate pro-survival autophagy through transcriptional activation of the mTOR inhibitor DDIT4. Determined the relationship between FTO alpha-ketoglutarate dependent dioxygenase (FTO), YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), and ATF4. Cyclic AMP-dependent transcription factor ATF-4 (ATF4) transcriptionally upregulated DDIT4 to suppress mTOR, which induced pro-survival autophagy during glutaminolysis inhibition." M6ADIS0059 39269733; 34373753 M6ADRUG0063 M6ACROT03338 REG00008 M6ATAR00185 Histone modification / Lactylation EPIREG00035 EPITAR00208 EPITAR00232 Down regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "Histone lactylation activates the transcription of YTHDF2 through p300-mediated Histone H3 lysine 18 lactylation (H3K18la) modification. In colorectal cancer, Glutaminolysis inhibition upregulated ATF4 expression in an m6A-dependent manner to activate pro-survival autophagy through transcriptional activation of the mTOR inhibitor DDIT4. Determined the relationship between FTO alpha-ketoglutarate dependent dioxygenase (FTO), YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), and ATF4. Cyclic AMP-dependent transcription factor ATF-4 (ATF4) transcriptionally upregulated DDIT4 to suppress mTOR, which induced pro-survival autophagy during glutaminolysis inhibition." M6ADIS0059 39269733; 34373753 M6ADRUG0003 M6ACROT03339 REG00008 M6ATAR00185 Histone modification / Lactylation EPIREG00035 EPITAR00208 EPITAR00232 Down regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "Histone lactylation activates the transcription of YTHDF2 through p300-mediated Histone H3 lysine 18 lactylation (H3K18la) modification. In colorectal cancer, Glutaminolysis inhibition upregulated ATF4 expression in an m6A-dependent manner to activate pro-survival autophagy through transcriptional activation of the mTOR inhibitor DDIT4. Determined the relationship between FTO alpha-ketoglutarate dependent dioxygenase (FTO), YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), and ATF4. ATF4 transcriptionally upregulated DDIT4 to suppress Cyclic AMP-dependent transcription factor ATF-4 (ATF4), which induced pro-survival autophagy during glutaminolysis inhibition." M6ADIS0059 39269733; 34373753 M6ADRUG0064 M6ACROT03340 REG00008 M6ATAR00339 Histone modification / Lactylation EPIREG00035 EPITAR00208 EPITAR00232 Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "Histone lactylation activates the transcription of YTHDF2 through p300-mediated Histone H3 lysine 18 lactylation (H3K18la) modification. In colorectal cancer, Glutaminolysis inhibition upregulated ATF4 expression in an m6A-dependent manner to activate pro-survival autophagy through transcriptional activation of the mTOR inhibitor DDIT4. Determined the relationship between FTO alpha-ketoglutarate dependent dioxygenase (FTO), YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), and ATF4. Serine/threonine-protein kinase mTOR (MTOR) transcriptionally upregulated DDIT4 to suppress mTOR, which induced pro-survival autophagy during glutaminolysis inhibition." M6ADIS0059 39269733; 34373753 M6ADRUG0044 M6ACROT03341 REG00008 M6ATAR00339 Histone modification / Lactylation EPIREG00035 EPITAR00208 EPITAR00232 Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "Histone lactylation activates the transcription of YTHDF2 through p300-mediated Histone H3 lysine 18 lactylation (H3K18la) modification. In colorectal cancer, Glutaminolysis inhibition upregulated ATF4 expression in an m6A-dependent manner to activate pro-survival autophagy through transcriptional activation of the mTOR inhibitor DDIT4. Determined the relationship between FTO alpha-ketoglutarate dependent dioxygenase (FTO), YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), and ATF4. ATF4 transcriptionally upregulated DDIT4 to suppress Serine/threonine-protein kinase mTOR (MTOR), which induced pro-survival autophagy during glutaminolysis inhibition." M6ADIS0059 39269733; 34373753 M6ADRUG0082 M6ACROT03342 REG00008 M6ATAR00339 Histone modification / Lactylation EPIREG00035 EPITAR00208 EPITAR00232 Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "Histone lactylation activates the transcription of YTHDF2 through p300-mediated Histone H3 lysine 18 lactylation (H3K18la) modification. In colorectal cancer, Glutaminolysis inhibition upregulated ATF4 expression in an m6A-dependent manner to activate pro-survival autophagy through transcriptional activation of the mTOR inhibitor DDIT4. Determined the relationship between FTO alpha-ketoglutarate dependent dioxygenase (FTO), YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), and ATF4. ATF4 transcriptionally upregulated DDIT4 to suppress Serine/threonine-protein kinase mTOR (MTOR), which induced pro-survival autophagy during glutaminolysis inhibition." M6ADIS0059 39269733; 34373753 M6ADRUG0073 M6ACROT03343 REG00008 M6ATAR00339 Histone modification / Lactylation EPIREG00035 EPITAR00208 EPITAR00232 Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "Histone lactylation activates the transcription of YTHDF2 through p300-mediated Histone H3 lysine 18 lactylation (H3K18la) modification. In colorectal cancer, Glutaminolysis inhibition upregulated ATF4 expression in an m6A-dependent manner to activate pro-survival autophagy through transcriptional activation of the mTOR inhibitor DDIT4. Determined the relationship between FTO alpha-ketoglutarate dependent dioxygenase (FTO), YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), and ATF4. Serine/threonine-protein kinase mTOR (MTOR) transcriptionally upregulated DDIT4 to suppress mTOR, which induced pro-survival autophagy during glutaminolysis inhibition." M6ADIS0059 39269733; 34373753 M6ADRUG0063 M6ACROT03344 REG00008 M6ATAR00339 Histone modification / Lactylation EPIREG00035 EPITAR00208 EPITAR00232 Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "Histone lactylation activates the transcription of YTHDF2 through p300-mediated Histone H3 lysine 18 lactylation (H3K18la) modification. In colorectal cancer, Glutaminolysis inhibition upregulated ATF4 expression in an m6A-dependent manner to activate pro-survival autophagy through transcriptional activation of the mTOR inhibitor DDIT4. Determined the relationship between FTO alpha-ketoglutarate dependent dioxygenase (FTO), YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), and ATF4. Serine/threonine-protein kinase mTOR (MTOR) transcriptionally upregulated DDIT4 to suppress mTOR, which induced pro-survival autophagy during glutaminolysis inhibition." M6ADIS0059 39269733; 34373753 M6ADRUG0003 M6ACROT03345 REG00008 M6ATAR00339 Histone modification / Lactylation EPIREG00035 EPITAR00208 EPITAR00232 Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "Histone lactylation activates the transcription of YTHDF2 through p300-mediated Histone H3 lysine 18 lactylation (H3K18la) modification. In colorectal cancer, Glutaminolysis inhibition upregulated ATF4 expression in an m6A-dependent manner to activate pro-survival autophagy through transcriptional activation of the mTOR inhibitor DDIT4. Determined the relationship between FTO alpha-ketoglutarate dependent dioxygenase (FTO), YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), and ATF4. ATF4 transcriptionally upregulated DDIT4 to suppress Serine/threonine-protein kinase mTOR (MTOR), which induced pro-survival autophagy during glutaminolysis inhibition." M6ADIS0059 39269733; 34373753 M6ADRUG0064 M6ACROT03346 REG00008 M6ATAR00524 Histone modification / Lactylation EPIREG00035 EPITAR00208 EPITAR00232 Down regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "Histone lactylation activates the transcription of YTHDF2 through p300-mediated Histone H3 lysine 18 lactylation (H3K18la) modification. In colorectal cancer, Mettl3- or Mettl14-deficient tumors increased cytotoxic tumor-infiltrating CD8+ T cells and elevated secretion of IFN-gamma, Cxcl9, and Cxcl10 in tumor microenvironment in vivo. Mechanistically, Mettl3 or Mettl14 loss promoted IFN-gamma-Stat1-Irf1 signaling through stabilizing the Transcription factor ISGF-3 components p91/p84 (Stat1) and Irf1 mRNA via Ythdf2." M6ADIS0059 39269733; 32964498 . M6ACROT03347 REG00008 M6ATAR00525 Histone modification / Lactylation EPIREG00035 EPITAR00208 EPITAR00232 Down regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "Histone lactylation activates the transcription of YTHDF2 through p300-mediated Histone H3 lysine 18 lactylation (H3K18la) modification. In colorectal cancer, Mettl3- or Mettl14-deficient tumors increased cytotoxic tumor-infiltrating CD8+ T cells and elevated secretion of IFN-gamma, Cxcl9, and Cxcl10 in tumor microenvironment in vivo. Mechanistically, Mettl3 or Mettl14 loss promoted IFN-gamma-Stat1-Irf1 signaling through stabilizing the Stat1 and Interferon regulatory factor 1 (Irf1) mRNA via Ythdf2." M6ADIS0059 39269733; 32964498 . M6ACROT03348 REG00008 M6ATAR00527 Histone modification / Lactylation EPIREG00035 EPITAR00208 EPITAR00232 Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "Histone lactylation activates the transcription of YTHDF2 through p300-mediated Histone H3 lysine 18 lactylation (H3K18la) modification. Knockdown of METTL14 significantly enhanced Arrestin domain-containing protein 4 (ARRDC4) mRNA stability relying on the ""reader"" protein YTHDF2 dependent manner in colorectal cancer." M6ADIS0059 39269733; 34916487 . M6ACROT03349 REG00008 M6ATAR00680 Histone modification / Lactylation EPIREG00035 EPITAR00208 EPITAR00232 Down regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "Histone lactylation activates the transcription of YTHDF2 through p300-mediated Histone H3 lysine 18 lactylation (H3K18la) modification. METTL3-catalyzed m6A modification in CRC tumorigenesis, wherein it facilitates CRC tumor growth and metastasis through suppressing Protein yippee-like 5 (YPEL5) expression in an m6A-YTHDF2-dependent manner." M6ADIS0059 39269733; 33411363 . M6ACROT03350 REG00008 M6ATAR00909 Histone modification / Lactylation EPIREG00035 EPITAR00208 EPITAR00232 Down regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator Histone lactylation activates the transcription of YTHDF2 through p300-mediated Histone H3 lysine 18 lactylation (H3K18la) modification. ALKBH5/YTHDF2-mediated m6A modification of Circ_AFF2 enhances radiosensitivity of colorectal cancer by inhibiting Cullin neddylation M6ADIS0059 39269733; 37381158 . M6ACROT03351 REG00008 M6ATAR01454 Histone modification / Lactylation EPIREG00035 EPITAR00208 EPITAR00232 Down regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "Histone lactylation activates the transcription of YTHDF2 through p300-mediated Histone H3 lysine 18 lactylation (H3K18la) modification. Apoptosis regulatory protein Siva (SIVA1), a critical apoptotic gene, as a key downstream target of the FTO-mediated m6A demethylation. The m6A demethylation of SIVA1 at the CDS region induced its mRNA degradation via a YTHDF2-dependent mechanism.FTO inhibition may restore the sensitivity of chemo-resistant CRC cells to 5-FU." M6ADIS0059 39269733; 36307991 M6ADRUG0005 M6ACROT03352 REG00008 M6ATAR00917 Histone modification / Lactylation EPIREG00035 EPITAR00208 EPITAR00232 Down regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "Histone lactylation activates the transcription of YTHDF2 through p300-mediated Histone H3 lysine 18 lactylation (H3K18la) modification. Mechanistically, Ras-related protein Rab-5A (RAB5A) was identified as the downstream target of ALKBH5 in CRC development, and ALKBH5 posttranscriptionally activated RAB5A by m6A demethylation, which impeded the YTHDF2-mediated degradation of RAB5A mRNA. In addition, we demonstrated that dysregulation of the ALKBH5-RAB5A axis could affect the tumourigenicity of CRC." M6ADIS0059 39269733; 37203239 . M6ACROT03353 REG00009 M6ATAR01335 Histone modification / Acetylation EPIREG00035 EPITAR00203 EPITAR00269 . Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "Histone acetyltransferase p300 promotes WTAP transcription through Histone H3 lysine 27 acetylation (H3K27ac). WTAP-mediated N6-methyladenosine modification of NLRP3 mRNA in kidney injury of diabetic nephropathy.WTAP expression in HK-2 cells was examined with the introduction of C646, a histone acetyltransferase p300 inhibitor.the expression change pattern of Dickkopf-related protein 3 (DKK3) under DN circumstances is in line with those of METTL14 and WTAP. DKK3's m6A methylation sites were confirmed to be located in the 3'UTR region, which is how METTL14 and WTAP improved DKK3's mRNA stability. Finally, YTHDF1, a m6A reader, was demonstrated to recognize m6A-methylated DKK3 and promote DKK3 expression." M6ADIS0117 35761192; 39151294 M6ADRUG0214 M6ACROT03354 REG00024 M6ATAR01335 Histone modification / Acetylation EPIREG00035 EPITAR00203 EPITAR00269 . Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "Histone acetyltransferase p300 promotes WTAP transcription through Histone H3 lysine 27 acetylation (H3K27ac). WTAP-mediated N6-methyladenosine modification of NLRP3 mRNA in kidney injury of diabetic nephropathy.WTAP expression in HK-2 cells was examined with the introduction of C646, a histone acetyltransferase p300 inhibitor.the expression change pattern of Dickkopf-related protein 3 (DKK3) under DN circumstances is in line with those of METTL14 and WTAP. DKK3's m6A methylation sites were confirmed to be located in the 3'UTR region, which is how METTL14 and WTAP improved DKK3's mRNA stability. Finally, YTHDF1, a m6A reader, was demonstrated to recognize m6A-methylated DKK3 and promote DKK3 expression." M6ADIS0117 35761192; 39151294 M6ADRUG0214 M6ACROT03355 REG00005 M6ATAR00140 Histone modification / Acetylation EPIREG00062 EPITAR00203 EPITAR00183 Up regulation Histone modification Direct Inhibition m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "Mechanically, HDAC2-reduced Histone H3 lysine 27 acetylation (H3K27ac) inhibits ALKBH5 transcription in CRC, whereas ectopic ALKBH5 expression decreases tumorigenesis of CRC cells and protects mice from colitis-associated tumor development.METTL14/ALKBH5/IGF2BPs combine to modulate JMJD8 stability in an m6A-dependent manner, which increases glycolysis and accelerates the development of CRC by enhancing the enzymatic activity of PKM2. ALKBH5 knockdown suppressed malignant behavior of colon cancer partially through Nuclear paraspeckle assembly transcript 1 (NEAT1) by demethylation in vitro and vivo, suggesting that ALKBH5-NEAT1 axis is a potential therapeutic target for colon cancer treatment." M6ADIS0059 37310898; 32913527 . M6ACROT03356 REG00005 M6ATAR00149 Histone modification / Acetylation EPIREG00062 EPITAR00203 EPITAR00183 Down regulation Histone modification Direct Inhibition m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "Mechanically, HDAC2-reduced Histone H3 lysine 27 acetylation (H3K27ac) inhibits ALKBH5 transcription in CRC, whereas ectopic ALKBH5 expression decreases tumorigenesis of CRC cells and protects mice from colitis-associated tumor development.METTL14/ALKBH5/IGF2BPs combine to modulate JMJD8 stability in an m6A-dependent manner, which increases glycolysis and accelerates the development of CRC by enhancing the enzymatic activity of PKM2. Overexpression of METTL3 upregulates Long intergenic non-protein coding RNA 2598 (LINC02598/RP11) expression in colorectal cancer cells. Overexpression of ALKBH5 downregulates RP11 expression." M6ADIS0059 37310898; 33335959 . M6ACROT03357 REG00005 M6ATAR00132 Histone modification / Acetylation EPIREG00062 EPITAR00203 EPITAR00183 . Histone modification Direct Inhibition m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "Mechanically, HDAC2-reduced Histone H3 lysine 27 acetylation (H3K27ac) inhibits ALKBH5 transcription in CRC, whereas ectopic ALKBH5 expression decreases tumorigenesis of CRC cells and protects mice from colitis-associated tumor development.METTL14/ALKBH5/IGF2BPs combine to modulate JMJD8 stability in an m6A-dependent manner, which increases glycolysis and accelerates the development of CRC by enhancing the enzymatic activity of PKM2. ALKBH5 plays an antitumor role in colorectal cancer by modulating the FOXO3/microRNA 21 (MIR21)/SPRY2 axis, which not only suggests a regulatory effect between ALKBH5 and FOXO3, but also provides a new therapeutic direction for colorectal cancer." M6ADIS0059 37310898; 34786052 . M6ACROT03358 REG00005 M6ATAR00260 Histone modification / Acetylation EPIREG00062 EPITAR00203 EPITAR00183 Down regulation Histone modification Direct Inhibition m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "Mechanically, HDAC2-reduced Histone H3 lysine 27 acetylation (H3K27ac) inhibits ALKBH5 transcription in CRC, whereas ectopic ALKBH5 expression decreases tumorigenesis of CRC cells and protects mice from colitis-associated tumor development.METTL14/ALKBH5/IGF2BPs combine to modulate JMJD8 stability in an m6A-dependent manner, which increases glycolysis and accelerates the development of CRC by enhancing the enzymatic activity of PKM2. ALKBH5 plays an antitumor role in colorectal cancer by modulating the Forkhead box protein O3 (FOXO3)/miR-21/SPRY2 axis, which not only suggests a regulatory effect between ALKBH5 and FOXO3, but also provides a new therapeutic direction for colorectal cancer." M6ADIS0059 37310898; 34786052 . M6ACROT03359 REG00005 M6ATAR00409 Histone modification / Acetylation EPIREG00062 EPITAR00203 EPITAR00183 Up regulation Histone modification Direct Inhibition m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "Mechanically, HDAC2-reduced Histone H3 lysine 27 acetylation (H3K27ac) inhibits ALKBH5 transcription in CRC, whereas ectopic ALKBH5 expression decreases tumorigenesis of CRC cells and protects mice from colitis-associated tumor development.METTL14/ALKBH5/IGF2BPs combine to modulate JMJD8 stability in an m6A-dependent manner, which increases glycolysis and accelerates the development of CRC by enhancing the enzymatic activity of PKM2. ALKBH5 plays an antitumor role in colorectal cancer by modulating the FOXO3/miR-21/Protein sprouty homolog 2 (SPRY2) axis, which not only suggests a regulatory effect between ALKBH5 and FOXO3, but also provides a new therapeutic direction for colorectal cancer." M6ADIS0059 37310898; 34786052 . M6ACROT03360 REG00005 M6ATAR00484 Histone modification / Acetylation EPIREG00062 EPITAR00203 EPITAR00183 Down regulation Histone modification Direct Inhibition m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "Mechanically, HDAC2-reduced Histone H3 lysine 27 acetylation (H3K27ac) inhibits ALKBH5 transcription in CRC, whereas ectopic ALKBH5 expression decreases tumorigenesis of CRC cells and protects mice from colitis-associated tumor development.METTL14/ALKBH5/IGF2BPs combine to modulate JMJD8 stability in an m6A-dependent manner, which increases glycolysis and accelerates the development of CRC by enhancing the enzymatic activity of PKM2. ALKBH5 was downregulated in CRC and ALKBH5 overexpression promoted ROS release and ferroptosis. ALKBH5 erased the m6A modification on Cystine/glutamate transporter (SLC7A11) mRNA to reduce the mRNA stability of SLC7A11, further reducing SLC7A11 expression. SLC7A11 overexpression reversed the promotive role of ALKBH5 overexpression in ferroptosis. ALKBH5 upregulation mitigated tumor growth in vivo." M6ADIS0059 37310898; 36820954 . M6ACROT03361 REG00005 M6ATAR00836 Histone modification / Acetylation EPIREG00062 EPITAR00203 EPITAR00183 Up regulation Histone modification Direct Inhibition m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "Mechanically, HDAC2-reduced Histone H3 lysine 27 acetylation (H3K27ac) inhibits ALKBH5 transcription in CRC, whereas ectopic ALKBH5 expression decreases tumorigenesis of CRC cells and protects mice from colitis-associated tumor development.METTL14/ALKBH5/IGF2BPs combine to modulate JMJD8 stability in an m6A-dependent manner, which increases glycolysis and accelerates the development of CRC by enhancing the enzymatic activity of PKM2. Tl increased the level of aberrant N6-methyladenosine (m6A) modification of Polyamine-transporting ATPase 13A3 (ATP13A3) via the METLL3/METTL14/ALKBH5-ATP13A5 axis to promote colorectal tumorigenesis." M6ADIS0059 37310898; 36745568 . M6ACROT03362 REG00005 M6ATAR00909 Histone modification / Acetylation EPIREG00062 EPITAR00203 EPITAR00183 Up regulation Histone modification Direct Inhibition m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "Mechanically, HDAC2-reduced Histone H3 lysine 27 acetylation (H3K27ac) inhibits ALKBH5 transcription in CRC, whereas ectopic ALKBH5 expression decreases tumorigenesis of CRC cells and protects mice from colitis-associated tumor development.METTL14/ALKBH5/IGF2BPs combine to modulate JMJD8 stability in an m6A-dependent manner, which increases glycolysis and accelerates the development of CRC by enhancing the enzymatic activity of PKM2. ALKBH5/YTHDF2-mediated m6A modification of Circ_AFF2 enhances radiosensitivity of colorectal cancer by inhibiting Cullin neddylation" M6ADIS0059 37310898; 37381158 . M6ACROT03363 REG00005 M6ATAR00917 Histone modification / Acetylation EPIREG00062 EPITAR00203 EPITAR00183 Up regulation Histone modification Direct Inhibition m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "Mechanically, HDAC2-reduced Histone H3 lysine 27 acetylation (H3K27ac) inhibits ALKBH5 transcription in CRC, whereas ectopic ALKBH5 expression decreases tumorigenesis of CRC cells and protects mice from colitis-associated tumor development.METTL14/ALKBH5/IGF2BPs combine to modulate JMJD8 stability in an m6A-dependent manner, which increases glycolysis and accelerates the development of CRC by enhancing the enzymatic activity of PKM2. Mechanistically, Ras-related protein Rab-5A (RAB5A) was identified as the downstream target of ALKBH5 in CRC development, and ALKBH5 posttranscriptionally activated RAB5A by m6A demethylation, which impeded the YTHDF2-mediated degradation of RAB5A mRNA. In addition, we demonstrated that dysregulation of the ALKBH5-RAB5A axis could affect the tumourigenicity of CRC." M6ADIS0059 37310898; 37203239 . M6ACROT03364 REG00005 M6ATAR00283 Histone modification / Acetylation EPIREG00062 EPITAR00203 EPITAR00183 Down regulation Histone modification Direct Inhibition m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "Mechanically, HDAC2-reduced Histone H3 lysine 27 acetylation (H3K27ac) inhibits ALKBH5 transcription in CRC, whereas ectopic ALKBH5 expression decreases tumorigenesis of CRC cells and protects mice from colitis-associated tumor development.METTL14/ALKBH5/IGF2BPs combine to modulate JMJD8 stability in an m6A-dependent manner, which increases glycolysis and accelerates the development of CRC by enhancing the enzymatic activity of PKM2. this study revealed the FTO-ALKBH5/IGF2BP2/Hexokinase-2 (HK2)/FOXO1 axis as a mechanism of aberrant m6A modification and glycolysis regulation in CRC." M6ADIS0059 37310898; 37580808 . M6ACROT03365 REG00005 M6ATAR00994 Histone modification / Acetylation EPIREG00062 EPITAR00203 EPITAR00183 . Histone modification Direct Inhibition m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "Mechanically, HDAC2-reduced Histone H3 lysine 27 acetylation (H3K27ac) inhibits ALKBH5 transcription in CRC, whereas ectopic ALKBH5 expression decreases tumorigenesis of CRC cells and protects mice from colitis-associated tumor development.METTL14/ALKBH5/IGF2BPs combine to modulate JMJD8 stability in an m6A-dependent manner, which increases glycolysis and accelerates the development of CRC by enhancing the enzymatic activity of PKM2. The rs11245997 A allele facilitated BET1-like protein (BET1L) expression by disrupting miR-140-3p binding. It also reduced BET1L m6A modification, which upregulated BET1L expression levels through a mechanism mediated by the m6A methyltransferases (METTL14 and WTAP) and the m6A demethylase ALKBH5." M6ADIS0059 37310898; 37115853 . M6ACROT03366 REG00005 M6ATAR00356 Histone modification / Acetylation EPIREG00062 EPITAR00203 EPITAR00183 Up regulation Histone modification Direct Inhibition m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "Mechanically, HDAC2-reduced Histone H3 lysine 27 acetylation (H3K27ac) inhibits ALKBH5 transcription in CRC, whereas ectopic ALKBH5 expression decreases tumorigenesis of CRC cells and protects mice from colitis-associated tumor development.METTL14/ALKBH5/IGF2BPs combine to modulate JMJD8 stability in an m6A-dependent manner, which increases glycolysis and accelerates the development of CRC by enhancing the enzymatic activity of PKM2. The interplay between CARMN and ALKBH5 promoted tumourigenesis in colorectal cancer patients via the Cellular tumor antigen p53 (TP53/p53)/ALKBH5/CARMN/miR-5683 pathway. These findings illuminate the role of m6A methylation in colorectal cancer patients with p53R273H mutation." M6ADIS0059 37310898; 39039912 . M6ACROT03367 REG00013 M6ATAR00283 Histone modification / Acetylation EPIREG00062 EPITAR00203 EPITAR00183 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "Mechanically, HDAC2-reduced Histone H3 lysine 27 acetylation (H3K27ac) inhibits ALKBH5 transcription in CRC, whereas ectopic ALKBH5 expression decreases tumorigenesis of CRC cells and protects mice from colitis-associated tumor development.METTL14/ALKBH5/IGF2BPs combine to modulate JMJD8 stability in an m6A-dependent manner, which increases glycolysis and accelerates the development of CRC by enhancing the enzymatic activity of PKM2.METTL3 stabilizes Hexokinase-2 (HK2) and SLC2A1 (GLUT1) expression in colorectal cancer through an m6A-IGF2BP2/3- dependent mechanism." M6ADIS0059 37310898; 32245489 . M6ACROT03368 REG00013 M6ATAR00283 Histone modification / Acetylation EPIREG00062 EPITAR00203 EPITAR00183 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "Mechanically, HDAC2-reduced Histone H3 lysine 27 acetylation (H3K27ac) inhibits ALKBH5 transcription in CRC, whereas ectopic ALKBH5 expression decreases tumorigenesis of CRC cells and protects mice from colitis-associated tumor development.METTL14/ALKBH5/IGF2BPs combine to modulate JMJD8 stability in an m6A-dependent manner, which increases glycolysis and accelerates the development of CRC by enhancing the enzymatic activity of PKM2.this study revealed the FTO-ALKBH5/IGF2BP2/Hexokinase-2 (HK2)/FOXO1 axis as a mechanism of aberrant m6A modification and glycolysis regulation in CRC." M6ADIS0059 37310898; 37580808 . M6ACROT03369 REG00014 M6ATAR00283 Histone modification / Acetylation EPIREG00062 EPITAR00203 EPITAR00183 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "Mechanically, HDAC2-reduced Histone H3 lysine 27 acetylation (H3K27ac) inhibits ALKBH5 transcription in CRC, whereas ectopic ALKBH5 expression decreases tumorigenesis of CRC cells and protects mice from colitis-associated tumor development.METTL14/ALKBH5/IGF2BPs combine to modulate JMJD8 stability in an m6A-dependent manner, which increases glycolysis and accelerates the development of CRC by enhancing the enzymatic activity of PKM2.METTL3 stabilizes Hexokinase-2 (HK2) and SLC2A1 (GLUT1) expression in colorectal cancer through an m6A-IGF2BP2/3- dependent mechanism." M6ADIS0059 37310898; 32245489 . M6ACROT03370 REG00005 M6ATAR00259 Histone modification / Methylation EPIREG00031 EPITAR00217 EPITAR00183 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "Polo like kinase 3 (PLK3) methylation decreases PLK3 phosphorylation of HIF1alpha and thereby increases HIF1alpha stability. HIF1alpha, in turn, upregulates ALKBH5 to reduce m6A modification of LINC00115, resulting in attenuated degradation of YTHDF2-dependent m6A-modified RNA and enhanced LINC00115 stability. Thus, this positive feedback loop provokes BCSC phenotypes and enhances chemoresistance and metastasis in triple-negative breast cancer. SETDB1 inhibitor TTD-IN with LINC00115 ASO sensitizes PTX-resistant cell response to chemotherapy in a xenograft animal model. Correlative expression of LINC00115, methylation PLK3, SETDB1, and HIF1alpha are prognostic for clinical triple-negative breast cancers.In conclusion, we demonstrated a critical function of ALKBH5-mediated m6A demethylation of Forkhead box protein O1 (FOXO1) mRNA in restoring redox balance, which in turn promoting CSCs characteristics and DOX resistance in TNBC, and suggested that targeting the ALKBH5/FOXO1 axis has therapeutic potential for patients with TNBC refractory to chemotherapy." M6ADIS0184 38520019; 38104484 M6ADRUG0022 M6ACROT03371 REG00007 M6ATAR00766 Histone modification / Lactylation . EPITAR00208 EPITAR00473 Up regulation Histone modification Indirect Enhancement m6A Histone modification indirectly regulates m6A modification through downstream signaling pathways "AP001885.4 was overexpressed in ESCC cells because of a higher Histone H3 lysine 18 lactylation (H3K18la) level in the promoter and amplification, then enhanced histone lactylation- and NF-kappaB (p65)-dependent transcription activation and METTL3-mediated mRNA stability of c-myc eventually upregulated c-myc and promoted cell proliferation L-glutamine amidohydrolase (GLS2) as a downstream target of METTL3. These findings uncover METTL3/GLS2 signaling as a potential therapeutic target in antimetastatic strategies against esophageal Squamous Cell Carcinoma(ESCC)." M6ADIS0056 39502790; 34094960 . M6ACROT03372 REG00007 M6ATAR00213 Histone modification / Lactylation . EPITAR00208 EPITAR00473 Down regulation Histone modification Indirect Enhancement m6A Histone modification indirectly regulates m6A modification through downstream signaling pathways "AP001885.4 was overexpressed in ESCC cells because of a higher Histone H3 lysine 18 lactylation (H3K18la) level in the promoter and amplification, then enhanced histone lactylation- and NF-kappaB (p65)-dependent transcription activation and METTL3-mediated mRNA stability of c-myc eventually upregulated c-myc and promoted cell proliferation METTL3 modulates the cell cycle of Esophageal squamous cell carcinoma(ESCC) cells through a Cyclin-dependent kinase inhibitor 1 (CDKN1A)-dependent pattern. METTL3-guided m6A modification contributes to the progression of ESCC via the p21-axis." M6ADIS0056 39502790; 34624569 . M6ACROT03373 REG00007 M6ATAR00351 Histone modification / Lactylation . EPITAR00208 EPITAR00473 Up regulation Histone modification Indirect Enhancement m6A Histone modification indirectly regulates m6A modification through downstream signaling pathways "AP001885.4 was overexpressed in ESCC cells because of a higher Histone H3 lysine 18 lactylation (H3K18la) level in the promoter and amplification, then enhanced histone lactylation- and NF-kappaB (p65)-dependent transcription activation and METTL3-mediated mRNA stability of c-myc eventually upregulated c-myc and promoted cell proliferation METTL3-catalyzed m6A modification promotes Neurogenic locus notch homolog protein 1 (NOTCH1) expression and the activation of the Notch signaling pathway. Forced activation of Notch signaling pathway successfully rescues the growth, migration, and invasion capacities of METTL3-depleted ESCC cells." M6ADIS0056 39502790; 34513313 . M6ACROT03374 REG00007 M6ATAR00228 Histone modification / Lactylation . EPITAR00208 EPITAR00473 Up regulation Histone modification Indirect Enhancement m6A Histone modification indirectly regulates m6A modification through downstream signaling pathways "AP001885.4 was overexpressed in ESCC cells because of a higher Histone H3 lysine 18 lactylation (H3K18la) level in the promoter and amplification, then enhanced histone lactylation- and NF-kappaB (p65)-dependent transcription activation and METTL3-mediated mRNA stability of c-myc eventually upregulated c-myc and promoted cell proliferation METTL3 could interact with Microprocessor complex subunit DGCR8 (DGCR8) protein and positively modulate pri-miR-320b maturation process in an N6-methyladenosine (m6A)-dependent manner. Therefore, our findings uncover a VEGF-C-independent mechanism of exosomal and intracellular miR-320b-mediated LN metastasis and identify miR-320b as a novel predictive marker and therapeutic target for LN metastasis in ESCC." M6ADIS0056 39502790; 34729394 . M6ACROT03375 REG00007 M6ATAR00047 Histone modification / Lactylation . EPITAR00208 EPITAR00473 Up regulation Histone modification Indirect Enhancement m6A Histone modification indirectly regulates m6A modification through downstream signaling pathways "AP001885.4 was overexpressed in ESCC cells because of a higher Histone H3 lysine 18 lactylation (H3K18la) level in the promoter and amplification, then enhanced histone lactylation- and NF-kappaB (p65)-dependent transcription activation and METTL3-mediated mRNA stability of c-myc eventually upregulated c-myc and promoted cell proliferation METTL3 could interact with DGCR8 protein and positively modulate pri-miR-320b maturation process in an N6-methyladenosine (m6A)-dependent manner. Therefore, our findings uncover a VEGF-C-independent mechanism of exosomal and intracellular hsa-miR-320b-mediated LN metastasis and identify miR-320b as a novel predictive marker and therapeutic target for LN metastasis in ESCC." M6ADIS0056 39502790; 34729394 . M6ACROT03376 REG00007 M6ATAR01390 Histone modification / Lactylation . EPITAR00208 EPITAR00473 . Histone modification Indirect Enhancement m6A Histone modification indirectly regulates m6A modification through downstream signaling pathways "AP001885.4 was overexpressed in ESCC cells because of a higher Histone H3 lysine 18 lactylation (H3K18la) level in the promoter and amplification, then enhanced histone lactylation- and NF-kappaB (p65)-dependent transcription activation and METTL3-mediated mRNA stability of c-myc eventually upregulated c-myc and promoted cell proliferation ESCC cells readily harness exogenous methionine to generate S-adenosyl-methionine (SAM), thus promoting cell proliferation. Mechanistically, methionine augments METTL3-mediated RNA m6A methylation through SAM and revises gene expression. Integrative omics analysis highlights the potent influence of methionine/SAM on Nuclear receptor subfamily 4 group A member 2 (NR4A2) expression in a tumor-specific manner, mediated by the IGF2BP2-dependent stabilization of methylated NR4A2 mRNA. We demonstrate that NR4A2 facilitates ESCC growth and negatively impacts patient survival." M6ADIS0056 39502790; 38570607 M6ADRUG0175 M6ACROT03377 REG00007 M6ATAR00368 Histone modification / Acetylation . EPITAR00203 EPITAR00474 Up regulation Histone modification Indirect Inhibition m6A Histone modification indirectly regulates m6A modification through downstream signaling pathways "Gain of H3K4me1 and Histone H3 lysine 27 acetylation (H3K27ac) led to the activation of MIR570HG expression. LINC00969 interacts with EZH2 and METTL3, transcriptionally regulates the level of H3K27me3 in the NLRP3 promoter region, and posttranscriptionally modifies the m6A level of NLRP3 in an m6A-YTHDF2-dependent manner miR-600 inhibited lung cancer via down-regulating METTL3 expression, and knockdown of METTL3 was used as a novel strategy for lung cancer therapy. The PI3-kinase subunit alpha (PI3k/PIK3CA)/Akt pathway is implicated in cell growth and survival and we also observed that knockdown of METTL3 changed the expression and phosphorylation of proteins of PI3K signaling pathway members." M6ADIS0007 37156816; 30774445 M6ADRUG0030 M6ACROT03378 REG00007 M6ATAR00017 Histone modification / Acetylation . EPITAR00203 EPITAR00474 Down regulation Histone modification Indirect Inhibition m6A Histone modification indirectly regulates m6A modification through downstream signaling pathways "Gain of H3K4me1 and Histone H3 lysine 27 acetylation (H3K27ac) led to the activation of MIR570HG expression. LINC00969 interacts with EZH2 and METTL3, transcriptionally regulates the level of H3K27me3 in the NLRP3 promoter region, and posttranscriptionally modifies the m6A level of NLRP3 in an m6A-YTHDF2-dependent manner m6A methyltransferase Mettl3 can increase the splicing of precursor hsa-miR-143-3p to facilitate its biogenesis. The miR-143-3p/VASH1 axis in BM of lung cancers and suggests their critical roles in lung cancer pathogenesis." M6ADIS0007 37156816; 31823788 M6ADRUG0030 M6ACROT03379 REG00007 M6ATAR00302 Histone modification / Acetylation . EPITAR00203 EPITAR00474 Up regulation Histone modification Indirect Inhibition m6A Histone modification indirectly regulates m6A modification through downstream signaling pathways "Gain of H3K4me1 and Histone H3 lysine 27 acetylation (H3K27ac) led to the activation of MIR570HG expression. LINC00969 interacts with EZH2 and METTL3, transcriptionally regulates the level of H3K27me3 in the NLRP3 promoter region, and posttranscriptionally modifies the m6A level of NLRP3 in an m6A-YTHDF2-dependent manner m6A methyltransferase METTL3 is indispensable for TGF-beta-induced EMT of lung cancer cells through the regulation of Transcription factor JunB (JUNB)." M6ADIS0007 37156816; 31982139 M6ADRUG0030 M6ACROT03380 REG00007 M6ATAR00485 Histone modification / Acetylation . EPITAR00203 EPITAR00474 . Histone modification Indirect Inhibition m6A Histone modification indirectly regulates m6A modification through downstream signaling pathways "Gain of H3K4me1 and Histone H3 lysine 27 acetylation (H3K27ac) led to the activation of MIR570HG expression. LINC00969 interacts with EZH2 and METTL3, transcriptionally regulates the level of H3K27me3 in the NLRP3 promoter region, and posttranscriptionally modifies the m6A level of NLRP3 in an m6A-YTHDF2-dependent manner the participation of Metformin decreased the bindings of DNMT3A/b to the METTL3 promoter with the help of the readers of NKAP and HNRNPA2B1.the mediation of m6A formation on pri-Let-7b processing increased the mature microRNA let-7b (MIRLET7B), whose key role is to suppress the Notch signaling and to re-captivate the Osimertinib treatment.The findings open up future drug development, targeting this pathway for lung cancer patients." M6ADIS0007 37156816; 35070958 M6ADRUG0090 M6ACROT03381 REG00007 M6ATAR00249 Histone modification / Acetylation . EPITAR00203 EPITAR00474 Up regulation Histone modification Indirect Inhibition m6A Histone modification indirectly regulates m6A modification through downstream signaling pathways "Gain of H3K4me1 and Histone H3 lysine 27 acetylation (H3K27ac) led to the activation of MIR570HG expression. LINC00969 interacts with EZH2 and METTL3, transcriptionally regulates the level of H3K27me3 in the NLRP3 promoter region, and posttranscriptionally modifies the m6A level of NLRP3 in an m6A-YTHDF2-dependent manner Simvastatin induces METTL3 down-regulation in lung cancer tissues, which further influences EMT via m6A modification on Histone-lysine N-methyltransferase EZH2 (EZH2) mRNA and thus inhibits the malignant progression of lung cancer." M6ADIS0007 37156816; 32373962 M6ADRUG0211 M6ACROT03382 REG00007 M6ATAR00325 Histone modification / Acetylation . EPITAR00203 EPITAR00474 Up regulation Histone modification Indirect Inhibition m6A Histone modification indirectly regulates m6A modification through downstream signaling pathways "Gain of H3K4me1 and Histone H3 lysine 27 acetylation (H3K27ac) led to the activation of MIR570HG expression. LINC00969 interacts with EZH2 and METTL3, transcriptionally regulates the level of H3K27me3 in the NLRP3 promoter region, and posttranscriptionally modifies the m6A level of NLRP3 in an m6A-YTHDF2-dependent manner METTL3 combines with Hepatocyte growth factor receptor (c-Met/MET) and causes the PI3K/AKT signalling pathway to be manipulated, which affects the sensitivity of lung cancer cells to gefitinib. METTL3 knockdown promotes apoptosis and inhibits proliferation of lung cancer cells." M6ADIS0007 37156816; 33491264 M6ADRUG0030 M6ACROT03383 REG00007 M6ATAR00553 Histone modification / Acetylation . EPITAR00203 EPITAR00474 Down regulation Histone modification Indirect Inhibition m6A Histone modification indirectly regulates m6A modification through downstream signaling pathways "Gain of H3K4me1 and Histone H3 lysine 27 acetylation (H3K27ac) led to the activation of MIR570HG expression. LINC00969 interacts with EZH2 and METTL3, transcriptionally regulates the level of H3K27me3 in the NLRP3 promoter region, and posttranscriptionally modifies the m6A level of NLRP3 in an m6A-YTHDF2-dependent manner METTL3-mediated m6A modification of Zinc finger and BTB domain-containing protein 4 (ZBTB4) via EZH2 is involved in the CS-induced EMT and in lung cancer. " M6ADIS0007 37156816; 33510938 M6ADRUG0030 M6ACROT03384 REG00007 M6ATAR00375 Histone modification / Acetylation . EPITAR00203 EPITAR00474 Down regulation Histone modification Indirect Inhibition m6A Histone modification indirectly regulates m6A modification through downstream signaling pathways "Gain of H3K4me1 and Histone H3 lysine 27 acetylation (H3K27ac) led to the activation of MIR570HG expression. LINC00969 interacts with EZH2 and METTL3, transcriptionally regulates the level of H3K27me3 in the NLRP3 promoter region, and posttranscriptionally modifies the m6A level of NLRP3 in an m6A-YTHDF2-dependent manner Bete-elemene exerted the restrictive impacts on the cell growth of lung cancer in vivo and in vitro through targeting METTL3. Bete-elemene contributed to the augmented Mutated in multiple advanced cancers 1 (PTEN) expression via suppressing its m6A modification." M6ADIS0007 37156816; 35069732 M6ADRUG0030 M6ACROT03385 REG00007 M6ATAR00368 Histone modification / Acetylation . EPITAR00203 EPITAR00474 Up regulation Histone modification Indirect Inhibition m6A Histone modification indirectly regulates m6A modification through downstream signaling pathways "Gain of H3K4me1 and Histone H3 lysine 27 acetylation (H3K27ac) led to the activation of MIR570HG expression. LINC00969 interacts with EZH2 and METTL3, transcriptionally regulates the level of H3K27me3 in the NLRP3 promoter region, and posttranscriptionally modifies the m6A level of NLRP3 in an m6A-YTHDF2-dependent manner METTL3-mediated m6A methylation promotes lung cancer progression via activating PI3-kinase subunit alpha (PI3k/PIK3CA)/AKT/mTOR pathway." M6ADIS0007 37156816; 35434840 M6ADRUG0030 M6ACROT03386 REG00007 M6ATAR00175 Histone modification / Acetylation . EPITAR00203 EPITAR00474 Up regulation Histone modification Indirect Inhibition m6A Histone modification indirectly regulates m6A modification through downstream signaling pathways "Gain of H3K4me1 and Histone H3 lysine 27 acetylation (H3K27ac) led to the activation of MIR570HG expression. LINC00969 interacts with EZH2 and METTL3, transcriptionally regulates the level of H3K27me3 in the NLRP3 promoter region, and posttranscriptionally modifies the m6A level of NLRP3 in an m6A-YTHDF2-dependent manner METTL3-mediated m6A methylation promotes lung cancer progression via activating PI3K/RAC-alpha serine/threonine-protein kinase (AKT1)/mTOR pathway." M6ADIS0007 37156816; 35434840 M6ADRUG0030 M6ACROT03387 REG00007 M6ATAR00339 Histone modification / Acetylation . EPITAR00203 EPITAR00474 Up regulation Histone modification Indirect Inhibition m6A Histone modification indirectly regulates m6A modification through downstream signaling pathways "Gain of H3K4me1 and Histone H3 lysine 27 acetylation (H3K27ac) led to the activation of MIR570HG expression. LINC00969 interacts with EZH2 and METTL3, transcriptionally regulates the level of H3K27me3 in the NLRP3 promoter region, and posttranscriptionally modifies the m6A level of NLRP3 in an m6A-YTHDF2-dependent manner METTL3-mediated m6A methylation promotes lung cancer progression via activating PI3K/AKT/Serine/threonine-protein kinase mTOR (MTOR) pathway." M6ADIS0007 37156816; 35434840 M6ADRUG0030 M6ACROT03388 REG00007 M6ATAR00673 Histone modification / Acetylation . EPITAR00203 EPITAR00474 Up regulation Histone modification Indirect Inhibition m6A Histone modification indirectly regulates m6A modification through downstream signaling pathways "Gain of H3K4me1 and Histone H3 lysine 27 acetylation (H3K27ac) led to the activation of MIR570HG expression. LINC00969 interacts with EZH2 and METTL3, transcriptionally regulates the level of H3K27me3 in the NLRP3 promoter region, and posttranscriptionally modifies the m6A level of NLRP3 in an m6A-YTHDF2-dependent manner The reduction in cell proliferation induced by SVIL antisense RNA 1 (SVIL-AS1) overexpression could be rescued by E2F1 overexpression or METTL3 knockdown. In conclusion, METTL3-induced SVIL-AS1 in LUAD, which connects m6A and lncRNA in lung cancer carcinogenesis." M6ADIS0007 37156816; 35068325 M6ADRUG0030 M6ACROT03389 REG00007 M6ATAR00890 Histone modification / Acetylation . EPITAR00203 EPITAR00474 Up regulation Histone modification Indirect Inhibition m6A Histone modification indirectly regulates m6A modification through downstream signaling pathways "Gain of H3K4me1 and Histone H3 lysine 27 acetylation (H3K27ac) led to the activation of MIR570HG expression. LINC00969 interacts with EZH2 and METTL3, transcriptionally regulates the level of H3K27me3 in the NLRP3 promoter region, and posttranscriptionally modifies the m6A level of NLRP3 in an m6A-YTHDF2-dependent manner METTL3 regulates the mRNA stability of SH3 domain-binding protein 5 (SH3BP5) in a YTHDF1-dependent manner, thereby impacting the invasive capacity of lung cancer cells." M6ADIS0007 37156816; 38141906 M6ADRUG0030 M6ACROT03390 REG00007 M6ATAR00368 Histone modification / Methylation . EPITAR00210 EPITAR00474 Up regulation Histone modification Indirect Inhibition m6A Histone modification indirectly regulates m6A modification through downstream signaling pathways "Gain of Histone H3 lysine 4 monomethylation (H3K4me1) and H3K27ac led to the activation of MIR570HG expression. LINC00969 interacts with EZH2 and METTL3, transcriptionally regulates the level of H3K27me3 in the NLRP3 promoter region, and posttranscriptionally modifies the m6A level of NLRP3 in an m6A-YTHDF2-dependent manner miR-600 inhibited lung cancer via down-regulating METTL3 expression, and knockdown of METTL3 was used as a novel strategy for lung cancer therapy. The PI3-kinase subunit alpha (PI3k/PIK3CA)/Akt pathway is implicated in cell growth and survival and we also observed that knockdown of METTL3 changed the expression and phosphorylation of proteins of PI3K signaling pathway members." M6ADIS0007 37156816; 30774445 M6ADRUG0030 M6ACROT03391 REG00007 M6ATAR00017 Histone modification / Methylation . EPITAR00210 EPITAR00474 Down regulation Histone modification Indirect Inhibition m6A Histone modification indirectly regulates m6A modification through downstream signaling pathways "Gain of Histone H3 lysine 4 monomethylation (H3K4me1) and H3K27ac led to the activation of MIR570HG expression. LINC00969 interacts with EZH2 and METTL3, transcriptionally regulates the level of H3K27me3 in the NLRP3 promoter region, and posttranscriptionally modifies the m6A level of NLRP3 in an m6A-YTHDF2-dependent manner m6A methyltransferase Mettl3 can increase the splicing of precursor hsa-miR-143-3p to facilitate its biogenesis. The miR-143-3p/VASH1 axis in BM of lung cancers and suggests their critical roles in lung cancer pathogenesis." M6ADIS0007 37156816; 31823788 M6ADRUG0030 M6ACROT03392 REG00007 M6ATAR00302 Histone modification / Methylation . EPITAR00210 EPITAR00474 Up regulation Histone modification Indirect Inhibition m6A Histone modification indirectly regulates m6A modification through downstream signaling pathways "Gain of Histone H3 lysine 4 monomethylation (H3K4me1) and H3K27ac led to the activation of MIR570HG expression. LINC00969 interacts with EZH2 and METTL3, transcriptionally regulates the level of H3K27me3 in the NLRP3 promoter region, and posttranscriptionally modifies the m6A level of NLRP3 in an m6A-YTHDF2-dependent manner m6A methyltransferase METTL3 is indispensable for TGF-beta-induced EMT of lung cancer cells through the regulation of Transcription factor JunB (JUNB)." M6ADIS0007 37156816; 31982139 M6ADRUG0030 M6ACROT03393 REG00007 M6ATAR00485 Histone modification / Methylation . EPITAR00210 EPITAR00474 . Histone modification Indirect Inhibition m6A Histone modification indirectly regulates m6A modification through downstream signaling pathways "Gain of Histone H3 lysine 4 monomethylation (H3K4me1) and H3K27ac led to the activation of MIR570HG expression. LINC00969 interacts with EZH2 and METTL3, transcriptionally regulates the level of H3K27me3 in the NLRP3 promoter region, and posttranscriptionally modifies the m6A level of NLRP3 in an m6A-YTHDF2-dependent manner the participation of Metformin decreased the bindings of DNMT3A/b to the METTL3 promoter with the help of the readers of NKAP and HNRNPA2B1.the mediation of m6A formation on pri-Let-7b processing increased the mature microRNA let-7b (MIRLET7B), whose key role is to suppress the Notch signaling and to re-captivate the Osimertinib treatment.The findings open up future drug development, targeting this pathway for lung cancer patients." M6ADIS0007 37156816; 35070958 M6ADRUG0090 M6ACROT03394 REG00007 M6ATAR00249 Histone modification / Methylation . EPITAR00210 EPITAR00474 Up regulation Histone modification Indirect Inhibition m6A Histone modification indirectly regulates m6A modification through downstream signaling pathways "Gain of Histone H3 lysine 4 monomethylation (H3K4me1) and H3K27ac led to the activation of MIR570HG expression. LINC00969 interacts with EZH2 and METTL3, transcriptionally regulates the level of H3K27me3 in the NLRP3 promoter region, and posttranscriptionally modifies the m6A level of NLRP3 in an m6A-YTHDF2-dependent manner Simvastatin induces METTL3 down-regulation in lung cancer tissues, which further influences EMT via m6A modification on Histone-lysine N-methyltransferase EZH2 (EZH2) mRNA and thus inhibits the malignant progression of lung cancer." M6ADIS0007 37156816; 32373962 M6ADRUG0211 M6ACROT03395 REG00007 M6ATAR00325 Histone modification / Methylation . EPITAR00210 EPITAR00474 Up regulation Histone modification Indirect Inhibition m6A Histone modification indirectly regulates m6A modification through downstream signaling pathways "Gain of Histone H3 lysine 4 monomethylation (H3K4me1) and H3K27ac led to the activation of MIR570HG expression. LINC00969 interacts with EZH2 and METTL3, transcriptionally regulates the level of H3K27me3 in the NLRP3 promoter region, and posttranscriptionally modifies the m6A level of NLRP3 in an m6A-YTHDF2-dependent manner METTL3 combines with Hepatocyte growth factor receptor (c-Met/MET) and causes the PI3K/AKT signalling pathway to be manipulated, which affects the sensitivity of lung cancer cells to gefitinib. METTL3 knockdown promotes apoptosis and inhibits proliferation of lung cancer cells." M6ADIS0007 37156816; 33491264 M6ADRUG0030 M6ACROT03396 REG00007 M6ATAR00553 Histone modification / Methylation . EPITAR00210 EPITAR00474 Down regulation Histone modification Indirect Inhibition m6A Histone modification indirectly regulates m6A modification through downstream signaling pathways "Gain of Histone H3 lysine 4 monomethylation (H3K4me1) and H3K27ac led to the activation of MIR570HG expression. LINC00969 interacts with EZH2 and METTL3, transcriptionally regulates the level of H3K27me3 in the NLRP3 promoter region, and posttranscriptionally modifies the m6A level of NLRP3 in an m6A-YTHDF2-dependent manner METTL3-mediated m6A modification of Zinc finger and BTB domain-containing protein 4 (ZBTB4) via EZH2 is involved in the CS-induced EMT and in lung cancer. " M6ADIS0007 37156816; 33510938 M6ADRUG0030 M6ACROT03397 REG00007 M6ATAR00375 Histone modification / Methylation . EPITAR00210 EPITAR00474 Down regulation Histone modification Indirect Inhibition m6A Histone modification indirectly regulates m6A modification through downstream signaling pathways "Gain of Histone H3 lysine 4 monomethylation (H3K4me1) and H3K27ac led to the activation of MIR570HG expression. LINC00969 interacts with EZH2 and METTL3, transcriptionally regulates the level of H3K27me3 in the NLRP3 promoter region, and posttranscriptionally modifies the m6A level of NLRP3 in an m6A-YTHDF2-dependent manner Bete-elemene exerted the restrictive impacts on the cell growth of lung cancer in vivo and in vitro through targeting METTL3. Bete-elemene contributed to the augmented Mutated in multiple advanced cancers 1 (PTEN) expression via suppressing its m6A modification." M6ADIS0007 37156816; 35069732 M6ADRUG0030 M6ACROT03398 REG00007 M6ATAR00368 Histone modification / Methylation . EPITAR00210 EPITAR00474 Up regulation Histone modification Indirect Inhibition m6A Histone modification indirectly regulates m6A modification through downstream signaling pathways "Gain of Histone H3 lysine 4 monomethylation (H3K4me1) and H3K27ac led to the activation of MIR570HG expression. LINC00969 interacts with EZH2 and METTL3, transcriptionally regulates the level of H3K27me3 in the NLRP3 promoter region, and posttranscriptionally modifies the m6A level of NLRP3 in an m6A-YTHDF2-dependent manner METTL3-mediated m6A methylation promotes lung cancer progression via activating PI3-kinase subunit alpha (PI3k/PIK3CA)/AKT/mTOR pathway." M6ADIS0007 37156816; 35434840 M6ADRUG0030 M6ACROT03399 REG00007 M6ATAR00175 Histone modification / Methylation . EPITAR00210 EPITAR00474 Up regulation Histone modification Indirect Inhibition m6A Histone modification indirectly regulates m6A modification through downstream signaling pathways "Gain of Histone H3 lysine 4 monomethylation (H3K4me1) and H3K27ac led to the activation of MIR570HG expression. LINC00969 interacts with EZH2 and METTL3, transcriptionally regulates the level of H3K27me3 in the NLRP3 promoter region, and posttranscriptionally modifies the m6A level of NLRP3 in an m6A-YTHDF2-dependent manner METTL3-mediated m6A methylation promotes lung cancer progression via activating PI3K/RAC-alpha serine/threonine-protein kinase (AKT1)/mTOR pathway." M6ADIS0007 37156816; 35434840 M6ADRUG0030 M6ACROT03400 REG00007 M6ATAR00339 Histone modification / Methylation . EPITAR00210 EPITAR00474 Up regulation Histone modification Indirect Inhibition m6A Histone modification indirectly regulates m6A modification through downstream signaling pathways "Gain of Histone H3 lysine 4 monomethylation (H3K4me1) and H3K27ac led to the activation of MIR570HG expression. LINC00969 interacts with EZH2 and METTL3, transcriptionally regulates the level of H3K27me3 in the NLRP3 promoter region, and posttranscriptionally modifies the m6A level of NLRP3 in an m6A-YTHDF2-dependent manner METTL3-mediated m6A methylation promotes lung cancer progression via activating PI3K/AKT/Serine/threonine-protein kinase mTOR (MTOR) pathway." M6ADIS0007 37156816; 35434840 M6ADRUG0030 M6ACROT03401 REG00007 M6ATAR00673 Histone modification / Methylation . EPITAR00210 EPITAR00474 Up regulation Histone modification Indirect Inhibition m6A Histone modification indirectly regulates m6A modification through downstream signaling pathways "Gain of Histone H3 lysine 4 monomethylation (H3K4me1) and H3K27ac led to the activation of MIR570HG expression. LINC00969 interacts with EZH2 and METTL3, transcriptionally regulates the level of H3K27me3 in the NLRP3 promoter region, and posttranscriptionally modifies the m6A level of NLRP3 in an m6A-YTHDF2-dependent manner The reduction in cell proliferation induced by SVIL antisense RNA 1 (SVIL-AS1) overexpression could be rescued by E2F1 overexpression or METTL3 knockdown. In conclusion, METTL3-induced SVIL-AS1 in LUAD, which connects m6A and lncRNA in lung cancer carcinogenesis." M6ADIS0007 37156816; 35068325 M6ADRUG0030 M6ACROT03402 REG00007 M6ATAR00890 Histone modification / Methylation . EPITAR00210 EPITAR00474 Up regulation Histone modification Indirect Inhibition m6A Histone modification indirectly regulates m6A modification through downstream signaling pathways "Gain of Histone H3 lysine 4 monomethylation (H3K4me1) and H3K27ac led to the activation of MIR570HG expression. LINC00969 interacts with EZH2 and METTL3, transcriptionally regulates the level of H3K27me3 in the NLRP3 promoter region, and posttranscriptionally modifies the m6A level of NLRP3 in an m6A-YTHDF2-dependent manner METTL3 regulates the mRNA stability of SH3 domain-binding protein 5 (SH3BP5) in a YTHDF1-dependent manner, thereby impacting the invasive capacity of lung cancer cells." M6ADIS0007 37156816; 38141906 M6ADRUG0030 M6ACROT03403 REG00005 M6ATAR00148 Histone modification / Methylation EPIREG00035 EPITAR00203 EPITAR00183 Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "E7 increased ALKBH5 expression through p300-mediated activation of the Histone H3 lysine 4 trimethylation (H3K4me3), as well as post-translational modification mediated by DDX3. ALKBH5-mediated m6A demethylation enhanced the expression of PAK5. The m6A reader YTHDF2 bound to PAK5 mRNA and regulated its stability in an m6A-dependent manner.The GAS5-AS1 expression in cervical cancer tissues was markedly decreased when compared with that in the adjacent normal tissues. GAS5-AS1 interacted with the tumor suppressor Growth arrest specific 5 (GAS5), and increased its stability by interacting with RNA demethylase ALKBH5 and decreasing GAS5 N6-methyladenosine (m6A) modification. m6A-mediated GAS5 RNA degradation relied on the m6A reader protein YTHDF2-dependent pathway. " M6ADIS0008 37480971; 31497208 . M6ACROT03404 REG00005 M6ATAR00964 Histone modification / Methylation EPIREG00035 EPITAR00203 EPITAR00183 Down regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "E7 increased ALKBH5 expression through p300-mediated activation of the Histone H3 lysine 4 trimethylation (H3K4me3), as well as post-translational modification mediated by DDX3. ALKBH5-mediated m6A demethylation enhanced the expression of PAK5. The m6A reader YTHDF2 bound to PAK5 mRNA and regulated its stability in an m6A-dependent manner.ALKBH5 demethylates and destabilizes NAD-dependent protein deacetylase sirtuin-3, mitochondrial (SIRT3) in an m6A-IGF2BP1-dependent manner, repressing CESC growth, lipid metabolism and tumorigenesis by downregulating ACC1." M6ADIS0008 37480971; 36705046 . M6ACROT03405 REG00008 M6ATAR00148 Histone modification / Methylation EPIREG00035 EPITAR00203 EPITAR00183 Up regulation Histone modification Indirect Inhibition m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "E7 increased ALKBH5 expression through p300-mediated activation of the Histone H3 lysine 4 trimethylation (H3K4me3), as well as post-translational modification mediated by DDX3. ALKBH5-mediated m6A demethylation enhanced the expression of PAK5. The m6A reader YTHDF2 bound to PAK5 mRNA and regulated its stability in an m6A-dependent manner.The GAS5-AS1 expression in cervical cancer tissues was markedly decreased when compared with that in the adjacent normal tissues. GAS5-AS1 interacted with the tumor suppressor Growth arrest specific 5 (GAS5), and increased its stability by interacting with RNA demethylase ALKBH5 and decreasing GAS5 N6-methyladenosine (m6A) modification. m6A-mediated GAS5 RNA degradation relied on the m6A reader protein YTHDF2-dependent pathway. " M6ADIS0008 37480971; 31497208 . M6ACROT03406 REG00005 M6ATAR00148 Histone modification / Acetylation EPIREG00066 EPITAR00204 EPITAR00183 Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "E7 increased ALKBH5 expression through WDR5-mediated activation of the Histone H3 lysine 27 acetylation (H3K27ac) histone modifications, as well as post-translational modification mediated by DDX3. ALKBH5-mediated m6A demethylation enhanced the expression of PAK5. The m6A reader YTHDF2 bound to PAK5 mRNA and regulated its stability in an m6A-dependent manner.The GAS5-AS1 expression in cervical cancer tissues was markedly decreased when compared with that in the adjacent normal tissues. GAS5-AS1 interacted with the tumor suppressor Growth arrest specific 5 (GAS5), and increased its stability by interacting with RNA demethylase ALKBH5 and decreasing GAS5 N6-methyladenosine (m6A) modification. m6A-mediated GAS5 RNA degradation relied on the m6A reader protein YTHDF2-dependent pathway. " M6ADIS0008 37480971; 31497208 . M6ACROT03407 REG00005 M6ATAR00964 Histone modification / Acetylation EPIREG00066 EPITAR00204 EPITAR00183 Down regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "E7 increased ALKBH5 expression through WDR5-mediated activation of the Histone H3 lysine 27 acetylation (H3K27ac) histone modifications, as well as post-translational modification mediated by DDX3. ALKBH5-mediated m6A demethylation enhanced the expression of PAK5. The m6A reader YTHDF2 bound to PAK5 mRNA and regulated its stability in an m6A-dependent manner.ALKBH5 demethylates and destabilizes NAD-dependent protein deacetylase sirtuin-3, mitochondrial (SIRT3) in an m6A-IGF2BP1-dependent manner, repressing CESC growth, lipid metabolism and tumorigenesis by downregulating ACC1." M6ADIS0008 37480971; 36705046 . M6ACROT03408 REG00008 M6ATAR00148 Histone modification / Acetylation EPIREG00066 EPITAR00204 EPITAR00183 Up regulation Histone modification Indirect Inhibition m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "E7 increased ALKBH5 expression through WDR5-mediated activation of the Histone H3 lysine 27 acetylation (H3K27ac) histone modifications, as well as post-translational modification mediated by DDX3. ALKBH5-mediated m6A demethylation enhanced the expression of PAK5. The m6A reader YTHDF2 bound to PAK5 mRNA and regulated its stability in an m6A-dependent manner.The GAS5-AS1 expression in cervical cancer tissues was markedly decreased when compared with that in the adjacent normal tissues. GAS5-AS1 interacted with the tumor suppressor Growth arrest specific 5 (GAS5), and increased its stability by interacting with RNA demethylase ALKBH5 and decreasing GAS5 N6-methyladenosine (m6A) modification. m6A-mediated GAS5 RNA degradation relied on the m6A reader protein YTHDF2-dependent pathway. " M6ADIS0008 37480971; 31497208 . M6ACROT03409 REG00008 M6ATAR00237 Histone modification / Methylation . EPITAR00204 EPITAR00232 Down regulation Histone modification Direct Enhancement m6A Histone modification directly impacts m6A modification through modulating the level of m6A regulator "Histone H3 lysine 4 trimethylation (H3K4me3) and H3K27ac modification in the promoter region of YTHDF2 enhanced its expression in HCC, and upregulated YTHDF2 in HCC predicted a worse prognosis.YTHDF2 recognized the m6A modification in the 5'-untranslational region of ETS variant transcription factor 5 (ETV5) mRNA and recruited eukaryotic translation initiation factor 3 subunit B to facilitate its translation. YTHDF2 acts as a tumor suppressor to repress cell proliferation and growth via destabilizing the Epidermal growth factor receptor (EGFR) mRNA in HCC." M6ADIS0006 38247171; 30423408 . M6ACROT03410 REG00008 M6ATAR00022 Histone modification / Methylation . EPITAR00204 EPITAR00232 Up regulation Histone modification Direct Enhancement m6A Histone modification directly impacts m6A modification through modulating the level of m6A regulator "Histone H3 lysine 4 trimethylation (H3K4me3) and H3K27ac modification in the promoter region of YTHDF2 enhanced its expression in HCC, and upregulated YTHDF2 in HCC predicted a worse prognosis.YTHDF2 recognized the m6A modification in the 5'-untranslational region of ETS variant transcription factor 5 (ETV5) mRNA and recruited eukaryotic translation initiation factor 3 subunit B to facilitate its translation. YTHDF2 promotes the CSC liver phenotype and cancer metastasis by modulating the m6A methylation of POU domain, class 5, transcription factor 1 (POU5F1) mRNA. YTHDF2 expression is positively correlated with OCT4 expression and m6A levels in the 5'-UTR of OCT4 mRNA in clinical hepatocellular carcinoma specimens." M6ADIS0006 38247171; 32366907 . M6ACROT03411 REG00008 M6ATAR00293 Histone modification / Methylation . EPITAR00204 EPITAR00232 Down regulation Histone modification Direct Enhancement m6A Histone modification directly impacts m6A modification through modulating the level of m6A regulator "Histone H3 lysine 4 trimethylation (H3K4me3) and H3K27ac modification in the promoter region of YTHDF2 enhanced its expression in HCC, and upregulated YTHDF2 in HCC predicted a worse prognosis.YTHDF2 recognized the m6A modification in the 5'-untranslational region of ETS variant transcription factor 5 (ETV5) mRNA and recruited eukaryotic translation initiation factor 3 subunit B to facilitate its translation. YTHDF2 processed the decay of m6A-containing Interleukin-11 (IL11) and serpin family E member 2 (SERPINE2) mRNAs. YTHDF2 transcription succumbed to hypoxia-inducible factor-2-alpha (HIF-2-alpha). Administration of a HIF-2-alpha antagonist (PT2385) restored YTHDF2-programed epigenetic machinery and repressed liver cancer." M6ADIS0006 38247171; 31735169 M6ADRUG0218 M6ACROT03412 REG00008 M6ATAR00266 Histone modification / Methylation . EPITAR00204 EPITAR00232 Down regulation Histone modification Direct Enhancement m6A Histone modification directly impacts m6A modification through modulating the level of m6A regulator "Histone H3 lysine 4 trimethylation (H3K4me3) and H3K27ac modification in the promoter region of YTHDF2 enhanced its expression in HCC, and upregulated YTHDF2 in HCC predicted a worse prognosis.YTHDF2 recognized the m6A modification in the 5'-untranslational region of ETS variant transcription factor 5 (ETV5) mRNA and recruited eukaryotic translation initiation factor 3 subunit B to facilitate its translation. YTHDF2 processed the decay of m6A-containing interleukin 11 (IL11) and Glia-derived nexin (SERPINE2) mRNAs. YTHDF2 transcription succumbed to hypoxia-inducible factor-2-alpha (HIF-2-alpha). Administration of a HIF-2-alpha antagonist (PT2385) restored YTHDF2-programed epigenetic machinery and repressed liver cancer." M6ADIS0006 38247171; 31735169 M6ADRUG0218 M6ACROT03413 REG00008 M6ATAR00494 Histone modification / Methylation . EPITAR00204 EPITAR00232 Up regulation Histone modification Direct Enhancement m6A Histone modification directly impacts m6A modification through modulating the level of m6A regulator "Histone H3 lysine 4 trimethylation (H3K4me3) and H3K27ac modification in the promoter region of YTHDF2 enhanced its expression in HCC, and upregulated YTHDF2 in HCC predicted a worse prognosis.YTHDF2 recognized the m6A modification in the 5'-untranslational region of ETS variant transcription factor 5 (ETV5) mRNA and recruited eukaryotic translation initiation factor 3 subunit B to facilitate its translation. YTHDF2 expression was associated positively with Splicing factor 3A subunit 3 (SF3A3) expression, which implied that they cooperate in LIHC progression. " M6ADIS0006 38247171; 33344502 . M6ACROT03414 REG00008 M6ATAR00511 Histone modification / Methylation . EPITAR00204 EPITAR00232 Up regulation Histone modification Direct Enhancement m6A Histone modification directly impacts m6A modification through modulating the level of m6A regulator "Histone H3 lysine 4 trimethylation (H3K4me3) and H3K27ac modification in the promoter region of YTHDF2 enhanced its expression in HCC, and upregulated YTHDF2 in HCC predicted a worse prognosis.YTHDF2 recognized the m6A modification in the 5'-untranslational region of ETS variant transcription factor 5 (ETV5) mRNA and recruited eukaryotic translation initiation factor 3 subunit B to facilitate its translation. PA2G4 plays a pro-metastatic role by increasing Tyrosine-protein kinase Fyn (FYN) expression through binding with YTHDF2 in HCC. PA2G4 becomes a reliable prognostic marker or therapeutic target for HCC patients." M6ADIS0006 38247171; 35526051 . M6ACROT03415 REG00008 M6ATAR00512 Histone modification / Methylation . EPITAR00204 EPITAR00232 Up regulation Histone modification Direct Enhancement m6A Histone modification directly impacts m6A modification through modulating the level of m6A regulator "Histone H3 lysine 4 trimethylation (H3K4me3) and H3K27ac modification in the promoter region of YTHDF2 enhanced its expression in HCC, and upregulated YTHDF2 in HCC predicted a worse prognosis.YTHDF2 recognized the m6A modification in the 5'-untranslational region of ETS variant transcription factor 5 (ETV5) mRNA and recruited eukaryotic translation initiation factor 3 subunit B to facilitate its translation. Proliferation-associated protein 2G4 (PA2G4) plays a pro-metastatic role by increasing FYN expression through binding with YTHDF2 in HCC. PA2G4 becomes a reliable prognostic marker or therapeutic target for HCC patients." M6ADIS0006 38247171; 35526051 . M6ACROT03416 REG00008 M6ATAR00659 Histone modification / Methylation . EPITAR00204 EPITAR00232 Down regulation Histone modification Direct Enhancement m6A Histone modification directly impacts m6A modification through modulating the level of m6A regulator "Histone H3 lysine 4 trimethylation (H3K4me3) and H3K27ac modification in the promoter region of YTHDF2 enhanced its expression in HCC, and upregulated YTHDF2 in HCC predicted a worse prognosis.YTHDF2 recognized the m6A modification in the 5'-untranslational region of ETS variant transcription factor 5 (ETV5) mRNA and recruited eukaryotic translation initiation factor 3 subunit B to facilitate its translation. Long intergenic non-protein coding RNA 1273 (LINC01273) was modified with m6A, METTL3 increased LINC01273 m6A modification, followed by LINC01273 decay in the presence of YTHDF2, a m6A 'reader'. And LINC01273 plays a key role in sorafenib resistant HCC cells." M6ADIS0006 38247171; 35037556 M6ADRUG0032 M6ACROT03417 REG00008 M6ATAR00269 Histone modification / Methylation . EPITAR00204 EPITAR00232 Down regulation Histone modification Direct Enhancement m6A Histone modification directly impacts m6A modification through modulating the level of m6A regulator "Histone H3 lysine 4 trimethylation (H3K4me3) and H3K27ac modification in the promoter region of YTHDF2 enhanced its expression in HCC, and upregulated YTHDF2 in HCC predicted a worse prognosis.YTHDF2 recognized the m6A modification in the 5'-untranslational region of ETS variant transcription factor 5 (ETV5) mRNA and recruited eukaryotic translation initiation factor 3 subunit B to facilitate its translation. FTO decreased m6A modification on mRNAs of glycolysis associated genes including Glucose transporter type 1 (GLUT1), PKM2, and c-Myc which alleviated the YTH N6-methyladenosine RNA binding protein 2 (YTHDF2)-mediated mRNA degradation. Therefore, the upregulated expression of FTO-IT1 leaded to overexpression of GLUT1, PKM2, and c-Myc by which enhanced glycolysis of HCC." M6ADIS0006 38247171; 37840133 . M6ACROT03418 REG00008 M6ATAR00312 Histone modification / Methylation . EPITAR00204 EPITAR00232 Down regulation Histone modification Direct Enhancement m6A Histone modification directly impacts m6A modification through modulating the level of m6A regulator "Histone H3 lysine 4 trimethylation (H3K4me3) and H3K27ac modification in the promoter region of YTHDF2 enhanced its expression in HCC, and upregulated YTHDF2 in HCC predicted a worse prognosis.YTHDF2 recognized the m6A modification in the 5'-untranslational region of ETS variant transcription factor 5 (ETV5) mRNA and recruited eukaryotic translation initiation factor 3 subunit B to facilitate its translation. FTO decreased m6A modification on mRNAs of glycolysis associated genes including GLUT1, Pyruvate kinase PKM (PKM2/PKM), and c-Myc which alleviated the YTH N6-methyladenosine RNA binding protein 2 (YTHDF2)-mediated mRNA degradation. Therefore, the upregulated expression of FTO-IT1 leaded to overexpression of GLUT1, PKM2, and c-Myc by which enhanced glycolysis of HCC." M6ADIS0006 38247171; 37840133 . M6ACROT03419 REG00008 M6ATAR00341 Histone modification / Methylation . EPITAR00204 EPITAR00232 Down regulation Histone modification Direct Enhancement m6A Histone modification directly impacts m6A modification through modulating the level of m6A regulator "Histone H3 lysine 4 trimethylation (H3K4me3) and H3K27ac modification in the promoter region of YTHDF2 enhanced its expression in HCC, and upregulated YTHDF2 in HCC predicted a worse prognosis.YTHDF2 recognized the m6A modification in the 5'-untranslational region of ETS variant transcription factor 5 (ETV5) mRNA and recruited eukaryotic translation initiation factor 3 subunit B to facilitate its translation. FTO decreased m6A modification on mRNAs of glycolysis associated genes including GLUT1, PKM2, and Myc proto-oncogene protein (MYC) which alleviated the YTH N6-methyladenosine RNA binding protein 2 (YTHDF2)-mediated mRNA degradation. Therefore, the upregulated expression of FTO-IT1 leaded to overexpression of GLUT1, PKM2, and c-Myc by which enhanced glycolysis of HCC." M6ADIS0006 38247171; 37840133 . M6ACROT03420 REG00008 M6ATAR00237 Histone modification / Acetylation . EPITAR00203 EPITAR00232 Down regulation Histone modification Direct Enhancement m6A Histone modification directly impacts m6A modification through modulating the level of m6A regulator "H3K4me3 and Histone H3 lysine 27 acetylation (H3K27ac) modification in the promoter region of YTHDF2 enhanced its expression in HCC, and upregulated YTHDF2 in HCC predicted a worse prognosis.YTHDF2 recognized the m6A modification in the 5'-untranslational region of ETS variant transcription factor 5 (ETV5) mRNA and recruited eukaryotic translation initiation factor 3 subunit B to facilitate its translation. YTHDF2 acts as a tumor suppressor to repress cell proliferation and growth via destabilizing the Epidermal growth factor receptor (EGFR) mRNA in HCC." M6ADIS0006 38247171; 30423408 . M6ACROT03421 REG00008 M6ATAR00022 Histone modification / Acetylation . EPITAR00203 EPITAR00232 Up regulation Histone modification Direct Enhancement m6A Histone modification directly impacts m6A modification through modulating the level of m6A regulator "H3K4me3 and Histone H3 lysine 27 acetylation (H3K27ac) modification in the promoter region of YTHDF2 enhanced its expression in HCC, and upregulated YTHDF2 in HCC predicted a worse prognosis.YTHDF2 recognized the m6A modification in the 5'-untranslational region of ETS variant transcription factor 5 (ETV5) mRNA and recruited eukaryotic translation initiation factor 3 subunit B to facilitate its translation. YTHDF2 promotes the CSC liver phenotype and cancer metastasis by modulating the m6A methylation of POU domain, class 5, transcription factor 1 (POU5F1) mRNA. YTHDF2 expression is positively correlated with OCT4 expression and m6A levels in the 5'-UTR of OCT4 mRNA in clinical hepatocellular carcinoma specimens." M6ADIS0006 38247171; 32366907 . M6ACROT03422 REG00008 M6ATAR00293 Histone modification / Acetylation . EPITAR00203 EPITAR00232 Down regulation Histone modification Direct Enhancement m6A Histone modification directly impacts m6A modification through modulating the level of m6A regulator "H3K4me3 and Histone H3 lysine 27 acetylation (H3K27ac) modification in the promoter region of YTHDF2 enhanced its expression in HCC, and upregulated YTHDF2 in HCC predicted a worse prognosis.YTHDF2 recognized the m6A modification in the 5'-untranslational region of ETS variant transcription factor 5 (ETV5) mRNA and recruited eukaryotic translation initiation factor 3 subunit B to facilitate its translation. YTHDF2 processed the decay of m6A-containing Interleukin-11 (IL11) and serpin family E member 2 (SERPINE2) mRNAs. YTHDF2 transcription succumbed to hypoxia-inducible factor-2-alpha (HIF-2-alpha). Administration of a HIF-2-alpha antagonist (PT2385) restored YTHDF2-programed epigenetic machinery and repressed liver cancer." M6ADIS0006 38247171; 31735169 M6ADRUG0218 M6ACROT03423 REG00008 M6ATAR00266 Histone modification / Acetylation . EPITAR00203 EPITAR00232 Down regulation Histone modification Direct Enhancement m6A Histone modification directly impacts m6A modification through modulating the level of m6A regulator "H3K4me3 and Histone H3 lysine 27 acetylation (H3K27ac) modification in the promoter region of YTHDF2 enhanced its expression in HCC, and upregulated YTHDF2 in HCC predicted a worse prognosis.YTHDF2 recognized the m6A modification in the 5'-untranslational region of ETS variant transcription factor 5 (ETV5) mRNA and recruited eukaryotic translation initiation factor 3 subunit B to facilitate its translation. YTHDF2 processed the decay of m6A-containing interleukin 11 (IL11) and Glia-derived nexin (SERPINE2) mRNAs. YTHDF2 transcription succumbed to hypoxia-inducible factor-2-alpha (HIF-2-alpha). Administration of a HIF-2-alpha antagonist (PT2385) restored YTHDF2-programed epigenetic machinery and repressed liver cancer." M6ADIS0006 38247171; 31735169 M6ADRUG0218 M6ACROT03424 REG00008 M6ATAR00494 Histone modification / Acetylation . EPITAR00203 EPITAR00232 Up regulation Histone modification Direct Enhancement m6A Histone modification directly impacts m6A modification through modulating the level of m6A regulator "H3K4me3 and Histone H3 lysine 27 acetylation (H3K27ac) modification in the promoter region of YTHDF2 enhanced its expression in HCC, and upregulated YTHDF2 in HCC predicted a worse prognosis.YTHDF2 recognized the m6A modification in the 5'-untranslational region of ETS variant transcription factor 5 (ETV5) mRNA and recruited eukaryotic translation initiation factor 3 subunit B to facilitate its translation. YTHDF2 expression was associated positively with Splicing factor 3A subunit 3 (SF3A3) expression, which implied that they cooperate in LIHC progression. " M6ADIS0006 38247171; 33344502 . M6ACROT03425 REG00008 M6ATAR00511 Histone modification / Acetylation . EPITAR00203 EPITAR00232 Up regulation Histone modification Direct Enhancement m6A Histone modification directly impacts m6A modification through modulating the level of m6A regulator "H3K4me3 and Histone H3 lysine 27 acetylation (H3K27ac) modification in the promoter region of YTHDF2 enhanced its expression in HCC, and upregulated YTHDF2 in HCC predicted a worse prognosis.YTHDF2 recognized the m6A modification in the 5'-untranslational region of ETS variant transcription factor 5 (ETV5) mRNA and recruited eukaryotic translation initiation factor 3 subunit B to facilitate its translation. PA2G4 plays a pro-metastatic role by increasing Tyrosine-protein kinase Fyn (FYN) expression through binding with YTHDF2 in HCC. PA2G4 becomes a reliable prognostic marker or therapeutic target for HCC patients." M6ADIS0006 38247171; 35526051 . M6ACROT03426 REG00008 M6ATAR00512 Histone modification / Acetylation . EPITAR00203 EPITAR00232 Up regulation Histone modification Direct Enhancement m6A Histone modification directly impacts m6A modification through modulating the level of m6A regulator "H3K4me3 and Histone H3 lysine 27 acetylation (H3K27ac) modification in the promoter region of YTHDF2 enhanced its expression in HCC, and upregulated YTHDF2 in HCC predicted a worse prognosis.YTHDF2 recognized the m6A modification in the 5'-untranslational region of ETS variant transcription factor 5 (ETV5) mRNA and recruited eukaryotic translation initiation factor 3 subunit B to facilitate its translation. Proliferation-associated protein 2G4 (PA2G4) plays a pro-metastatic role by increasing FYN expression through binding with YTHDF2 in HCC. PA2G4 becomes a reliable prognostic marker or therapeutic target for HCC patients." M6ADIS0006 38247171; 35526051 . M6ACROT03427 REG00008 M6ATAR00659 Histone modification / Acetylation . EPITAR00203 EPITAR00232 Down regulation Histone modification Direct Enhancement m6A Histone modification directly impacts m6A modification through modulating the level of m6A regulator "H3K4me3 and Histone H3 lysine 27 acetylation (H3K27ac) modification in the promoter region of YTHDF2 enhanced its expression in HCC, and upregulated YTHDF2 in HCC predicted a worse prognosis.YTHDF2 recognized the m6A modification in the 5'-untranslational region of ETS variant transcription factor 5 (ETV5) mRNA and recruited eukaryotic translation initiation factor 3 subunit B to facilitate its translation. Long intergenic non-protein coding RNA 1273 (LINC01273) was modified with m6A, METTL3 increased LINC01273 m6A modification, followed by LINC01273 decay in the presence of YTHDF2, a m6A 'reader'. And LINC01273 plays a key role in sorafenib resistant HCC cells." M6ADIS0006 38247171; 35037556 M6ADRUG0032 M6ACROT03428 REG00008 M6ATAR00269 Histone modification / Acetylation . EPITAR00203 EPITAR00232 Down regulation Histone modification Direct Enhancement m6A Histone modification directly impacts m6A modification through modulating the level of m6A regulator "H3K4me3 and Histone H3 lysine 27 acetylation (H3K27ac) modification in the promoter region of YTHDF2 enhanced its expression in HCC, and upregulated YTHDF2 in HCC predicted a worse prognosis.YTHDF2 recognized the m6A modification in the 5'-untranslational region of ETS variant transcription factor 5 (ETV5) mRNA and recruited eukaryotic translation initiation factor 3 subunit B to facilitate its translation. FTO decreased m6A modification on mRNAs of glycolysis associated genes including Glucose transporter type 1 (GLUT1), PKM2, and c-Myc which alleviated the YTH N6-methyladenosine RNA binding protein 2 (YTHDF2)-mediated mRNA degradation. Therefore, the upregulated expression of FTO-IT1 leaded to overexpression of GLUT1, PKM2, and c-Myc by which enhanced glycolysis of HCC." M6ADIS0006 38247171; 37840133 . M6ACROT03429 REG00008 M6ATAR00312 Histone modification / Acetylation . EPITAR00203 EPITAR00232 Down regulation Histone modification Direct Enhancement m6A Histone modification directly impacts m6A modification through modulating the level of m6A regulator "H3K4me3 and Histone H3 lysine 27 acetylation (H3K27ac) modification in the promoter region of YTHDF2 enhanced its expression in HCC, and upregulated YTHDF2 in HCC predicted a worse prognosis.YTHDF2 recognized the m6A modification in the 5'-untranslational region of ETS variant transcription factor 5 (ETV5) mRNA and recruited eukaryotic translation initiation factor 3 subunit B to facilitate its translation. FTO decreased m6A modification on mRNAs of glycolysis associated genes including GLUT1, Pyruvate kinase PKM (PKM2/PKM), and c-Myc which alleviated the YTH N6-methyladenosine RNA binding protein 2 (YTHDF2)-mediated mRNA degradation. Therefore, the upregulated expression of FTO-IT1 leaded to overexpression of GLUT1, PKM2, and c-Myc by which enhanced glycolysis of HCC." M6ADIS0006 38247171; 37840133 . M6ACROT03430 REG00008 M6ATAR00341 Histone modification / Acetylation . EPITAR00203 EPITAR00232 Down regulation Histone modification Direct Enhancement m6A Histone modification directly impacts m6A modification through modulating the level of m6A regulator "H3K4me3 and Histone H3 lysine 27 acetylation (H3K27ac) modification in the promoter region of YTHDF2 enhanced its expression in HCC, and upregulated YTHDF2 in HCC predicted a worse prognosis.YTHDF2 recognized the m6A modification in the 5'-untranslational region of ETS variant transcription factor 5 (ETV5) mRNA and recruited eukaryotic translation initiation factor 3 subunit B to facilitate its translation. FTO decreased m6A modification on mRNAs of glycolysis associated genes including GLUT1, PKM2, and Myc proto-oncogene protein (MYC) which alleviated the YTH N6-methyladenosine RNA binding protein 2 (YTHDF2)-mediated mRNA degradation. Therefore, the upregulated expression of FTO-IT1 leaded to overexpression of GLUT1, PKM2, and c-Myc by which enhanced glycolysis of HCC." M6ADIS0006 38247171; 37840133 . M6ACROT03431 REG00001 M6ATAR00341 Histone modification / Acetylation EPIREG00067 EPITAR00203 EPITAR00179 Up regulation Histone modification Direct Inhibition m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "HDACi reduces ferroptosis suppressor protein (FSP1) by promoting its mRNA degradation. Specifically, it is confirmed that HDACi specifically targets HDAC1 and promotes the Histone H3 lysine 27 acetylation (H3K27ac) modification of fat mass- and obesity-associated gene (FTO) and AlkB Homolog 5, RNA Demethylase (ALKBH5), which results in significant activation of FTO and ALKBH5. The activation of FTO and ALKBH5 reduces N6-methyladenosine (m6A) modification on FSP1 mRNA, leading to its degradation. Crucially, lactylation of HDAC1K412is essential for ferroptosis regulation. Both Vorinostat (SAHA) and Trichostatin A (TSA) notably diminish HDAC1K412lactylation in comparison to other HDAC1 inhibitors, exhibiting a consistent trend of increasing susceptibility to ferroptosis. miR-96 antagomir could potentially retard the cancerogenesis in colorectal cancer via AMPK-alpha-2-dependent inhibition of FTO and blocking FTO-mediated m6A modification of Myc proto-oncogene protein (MYC)." M6ADIS0059 39888307; 33183350 . M6ACROT03432 REG00001 M6ATAR00185 Histone modification / Acetylation EPIREG00067 EPITAR00203 EPITAR00179 . Histone modification Direct Inhibition m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "HDACi reduces ferroptosis suppressor protein (FSP1) by promoting its mRNA degradation. Specifically, it is confirmed that HDACi specifically targets HDAC1 and promotes the Histone H3 lysine 27 acetylation (H3K27ac) modification of fat mass- and obesity-associated gene (FTO) and AlkB Homolog 5, RNA Demethylase (ALKBH5), which results in significant activation of FTO and ALKBH5. The activation of FTO and ALKBH5 reduces N6-methyladenosine (m6A) modification on FSP1 mRNA, leading to its degradation. Crucially, lactylation of HDAC1K412is essential for ferroptosis regulation. Both Vorinostat (SAHA) and Trichostatin A (TSA) notably diminish HDAC1K412lactylation in comparison to other HDAC1 inhibitors, exhibiting a consistent trend of increasing susceptibility to ferroptosis. In colorectal cancer, Glutaminolysis inhibition upregulated ATF4 expression in an m6A-dependent manner to activate pro-survival autophagy through transcriptional activation of the mTOR inhibitor DDIT4. Determined the relationship between FTO alpha-ketoglutarate dependent dioxygenase (FTO), YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), and ATF4. Cyclic AMP-dependent transcription factor ATF-4 (ATF4) transcriptionally upregulated DDIT4 to suppress mTOR, which induced pro-survival autophagy during glutaminolysis inhibition." M6ADIS0059 39888307; 34373753 M6ADRUG0044 M6ACROT03433 REG00001 M6ATAR00185 Histone modification / Acetylation EPIREG00067 EPITAR00203 EPITAR00179 . Histone modification Direct Inhibition m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "HDACi reduces ferroptosis suppressor protein (FSP1) by promoting its mRNA degradation. Specifically, it is confirmed that HDACi specifically targets HDAC1 and promotes the Histone H3 lysine 27 acetylation (H3K27ac) modification of fat mass- and obesity-associated gene (FTO) and AlkB Homolog 5, RNA Demethylase (ALKBH5), which results in significant activation of FTO and ALKBH5. The activation of FTO and ALKBH5 reduces N6-methyladenosine (m6A) modification on FSP1 mRNA, leading to its degradation. Crucially, lactylation of HDAC1K412is essential for ferroptosis regulation. Both Vorinostat (SAHA) and Trichostatin A (TSA) notably diminish HDAC1K412lactylation in comparison to other HDAC1 inhibitors, exhibiting a consistent trend of increasing susceptibility to ferroptosis. In colorectal cancer, Glutaminolysis inhibition upregulated ATF4 expression in an m6A-dependent manner to activate pro-survival autophagy through transcriptional activation of the mTOR inhibitor DDIT4. Determined the relationship between FTO alpha-ketoglutarate dependent dioxygenase (FTO), YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), and ATF4. ATF4 transcriptionally upregulated DDIT4 to suppress Cyclic AMP-dependent transcription factor ATF-4 (ATF4), which induced pro-survival autophagy during glutaminolysis inhibition." M6ADIS0059 39888307; 34373753 M6ADRUG0082 M6ACROT03434 REG00001 M6ATAR00185 Histone modification / Acetylation EPIREG00067 EPITAR00203 EPITAR00179 . Histone modification Direct Inhibition m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "HDACi reduces ferroptosis suppressor protein (FSP1) by promoting its mRNA degradation. Specifically, it is confirmed that HDACi specifically targets HDAC1 and promotes the Histone H3 lysine 27 acetylation (H3K27ac) modification of fat mass- and obesity-associated gene (FTO) and AlkB Homolog 5, RNA Demethylase (ALKBH5), which results in significant activation of FTO and ALKBH5. The activation of FTO and ALKBH5 reduces N6-methyladenosine (m6A) modification on FSP1 mRNA, leading to its degradation. Crucially, lactylation of HDAC1K412is essential for ferroptosis regulation. Both Vorinostat (SAHA) and Trichostatin A (TSA) notably diminish HDAC1K412lactylation in comparison to other HDAC1 inhibitors, exhibiting a consistent trend of increasing susceptibility to ferroptosis. In colorectal cancer, Glutaminolysis inhibition upregulated ATF4 expression in an m6A-dependent manner to activate pro-survival autophagy through transcriptional activation of the mTOR inhibitor DDIT4. Determined the relationship between FTO alpha-ketoglutarate dependent dioxygenase (FTO), YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), and ATF4. Cyclic AMP-dependent transcription factor ATF-4 (ATF4) transcriptionally upregulated DDIT4 to suppress mTOR, which induced pro-survival autophagy during glutaminolysis inhibition." M6ADIS0059 39888307; 34373753 M6ADRUG0073 M6ACROT03435 REG00001 M6ATAR00185 Histone modification / Acetylation EPIREG00067 EPITAR00203 EPITAR00179 . Histone modification Direct Inhibition m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "HDACi reduces ferroptosis suppressor protein (FSP1) by promoting its mRNA degradation. Specifically, it is confirmed that HDACi specifically targets HDAC1 and promotes the Histone H3 lysine 27 acetylation (H3K27ac) modification of fat mass- and obesity-associated gene (FTO) and AlkB Homolog 5, RNA Demethylase (ALKBH5), which results in significant activation of FTO and ALKBH5. The activation of FTO and ALKBH5 reduces N6-methyladenosine (m6A) modification on FSP1 mRNA, leading to its degradation. Crucially, lactylation of HDAC1K412is essential for ferroptosis regulation. Both Vorinostat (SAHA) and Trichostatin A (TSA) notably diminish HDAC1K412lactylation in comparison to other HDAC1 inhibitors, exhibiting a consistent trend of increasing susceptibility to ferroptosis. In colorectal cancer, Glutaminolysis inhibition upregulated ATF4 expression in an m6A-dependent manner to activate pro-survival autophagy through transcriptional activation of the mTOR inhibitor DDIT4. Determined the relationship between FTO alpha-ketoglutarate dependent dioxygenase (FTO), YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), and ATF4. Cyclic AMP-dependent transcription factor ATF-4 (ATF4) transcriptionally upregulated DDIT4 to suppress mTOR, which induced pro-survival autophagy during glutaminolysis inhibition." M6ADIS0059 39888307; 34373753 M6ADRUG0063 M6ACROT03436 REG00001 M6ATAR00185 Histone modification / Acetylation EPIREG00067 EPITAR00203 EPITAR00179 . Histone modification Direct Inhibition m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "HDACi reduces ferroptosis suppressor protein (FSP1) by promoting its mRNA degradation. Specifically, it is confirmed that HDACi specifically targets HDAC1 and promotes the Histone H3 lysine 27 acetylation (H3K27ac) modification of fat mass- and obesity-associated gene (FTO) and AlkB Homolog 5, RNA Demethylase (ALKBH5), which results in significant activation of FTO and ALKBH5. The activation of FTO and ALKBH5 reduces N6-methyladenosine (m6A) modification on FSP1 mRNA, leading to its degradation. Crucially, lactylation of HDAC1K412is essential for ferroptosis regulation. Both Vorinostat (SAHA) and Trichostatin A (TSA) notably diminish HDAC1K412lactylation in comparison to other HDAC1 inhibitors, exhibiting a consistent trend of increasing susceptibility to ferroptosis. In colorectal cancer, Glutaminolysis inhibition upregulated ATF4 expression in an m6A-dependent manner to activate pro-survival autophagy through transcriptional activation of the mTOR inhibitor DDIT4. Determined the relationship between FTO alpha-ketoglutarate dependent dioxygenase (FTO), YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), and ATF4. ATF4 transcriptionally upregulated DDIT4 to suppress Cyclic AMP-dependent transcription factor ATF-4 (ATF4), which induced pro-survival autophagy during glutaminolysis inhibition." M6ADIS0059 39888307; 34373753 M6ADRUG0003 M6ACROT03437 REG00001 M6ATAR00185 Histone modification / Acetylation EPIREG00067 EPITAR00203 EPITAR00179 . Histone modification Direct Inhibition m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "HDACi reduces ferroptosis suppressor protein (FSP1) by promoting its mRNA degradation. Specifically, it is confirmed that HDACi specifically targets HDAC1 and promotes the Histone H3 lysine 27 acetylation (H3K27ac) modification of fat mass- and obesity-associated gene (FTO) and AlkB Homolog 5, RNA Demethylase (ALKBH5), which results in significant activation of FTO and ALKBH5. The activation of FTO and ALKBH5 reduces N6-methyladenosine (m6A) modification on FSP1 mRNA, leading to its degradation. Crucially, lactylation of HDAC1K412is essential for ferroptosis regulation. Both Vorinostat (SAHA) and Trichostatin A (TSA) notably diminish HDAC1K412lactylation in comparison to other HDAC1 inhibitors, exhibiting a consistent trend of increasing susceptibility to ferroptosis. In colorectal cancer, Glutaminolysis inhibition upregulated ATF4 expression in an m6A-dependent manner to activate pro-survival autophagy through transcriptional activation of the mTOR inhibitor DDIT4. Determined the relationship between FTO alpha-ketoglutarate dependent dioxygenase (FTO), YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), and ATF4. ATF4 transcriptionally upregulated DDIT4 to suppress Cyclic AMP-dependent transcription factor ATF-4 (ATF4), which induced pro-survival autophagy during glutaminolysis inhibition." M6ADIS0059 39888307; 34373753 M6ADRUG0064 M6ACROT03438 REG00001 M6ATAR00339 Histone modification / Acetylation EPIREG00067 EPITAR00203 EPITAR00179 . Histone modification Direct Inhibition m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "HDACi reduces ferroptosis suppressor protein (FSP1) by promoting its mRNA degradation. Specifically, it is confirmed that HDACi specifically targets HDAC1 and promotes the Histone H3 lysine 27 acetylation (H3K27ac) modification of fat mass- and obesity-associated gene (FTO) and AlkB Homolog 5, RNA Demethylase (ALKBH5), which results in significant activation of FTO and ALKBH5. The activation of FTO and ALKBH5 reduces N6-methyladenosine (m6A) modification on FSP1 mRNA, leading to its degradation. Crucially, lactylation of HDAC1K412is essential for ferroptosis regulation. Both Vorinostat (SAHA) and Trichostatin A (TSA) notably diminish HDAC1K412lactylation in comparison to other HDAC1 inhibitors, exhibiting a consistent trend of increasing susceptibility to ferroptosis. In colorectal cancer, Glutaminolysis inhibition upregulated ATF4 expression in an m6A-dependent manner to activate pro-survival autophagy through transcriptional activation of the mTOR inhibitor DDIT4. Determined the relationship between FTO alpha-ketoglutarate dependent dioxygenase (FTO), YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), and ATF4. Serine/threonine-protein kinase mTOR (MTOR) transcriptionally upregulated DDIT4 to suppress mTOR, which induced pro-survival autophagy during glutaminolysis inhibition." M6ADIS0059 39888307; 34373753 M6ADRUG0044 M6ACROT03439 REG00001 M6ATAR00339 Histone modification / Acetylation EPIREG00067 EPITAR00203 EPITAR00179 . Histone modification Direct Inhibition m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "HDACi reduces ferroptosis suppressor protein (FSP1) by promoting its mRNA degradation. Specifically, it is confirmed that HDACi specifically targets HDAC1 and promotes the Histone H3 lysine 27 acetylation (H3K27ac) modification of fat mass- and obesity-associated gene (FTO) and AlkB Homolog 5, RNA Demethylase (ALKBH5), which results in significant activation of FTO and ALKBH5. The activation of FTO and ALKBH5 reduces N6-methyladenosine (m6A) modification on FSP1 mRNA, leading to its degradation. Crucially, lactylation of HDAC1K412is essential for ferroptosis regulation. Both Vorinostat (SAHA) and Trichostatin A (TSA) notably diminish HDAC1K412lactylation in comparison to other HDAC1 inhibitors, exhibiting a consistent trend of increasing susceptibility to ferroptosis. In colorectal cancer, Glutaminolysis inhibition upregulated ATF4 expression in an m6A-dependent manner to activate pro-survival autophagy through transcriptional activation of the mTOR inhibitor DDIT4. Determined the relationship between FTO alpha-ketoglutarate dependent dioxygenase (FTO), YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), and ATF4. ATF4 transcriptionally upregulated DDIT4 to suppress Serine/threonine-protein kinase mTOR (MTOR), which induced pro-survival autophagy during glutaminolysis inhibition." M6ADIS0059 39888307; 34373753 M6ADRUG0082 M6ACROT03440 REG00001 M6ATAR00339 Histone modification / Acetylation EPIREG00067 EPITAR00203 EPITAR00179 . Histone modification Direct Inhibition m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "HDACi reduces ferroptosis suppressor protein (FSP1) by promoting its mRNA degradation. Specifically, it is confirmed that HDACi specifically targets HDAC1 and promotes the Histone H3 lysine 27 acetylation (H3K27ac) modification of fat mass- and obesity-associated gene (FTO) and AlkB Homolog 5, RNA Demethylase (ALKBH5), which results in significant activation of FTO and ALKBH5. The activation of FTO and ALKBH5 reduces N6-methyladenosine (m6A) modification on FSP1 mRNA, leading to its degradation. Crucially, lactylation of HDAC1K412is essential for ferroptosis regulation. Both Vorinostat (SAHA) and Trichostatin A (TSA) notably diminish HDAC1K412lactylation in comparison to other HDAC1 inhibitors, exhibiting a consistent trend of increasing susceptibility to ferroptosis. In colorectal cancer, Glutaminolysis inhibition upregulated ATF4 expression in an m6A-dependent manner to activate pro-survival autophagy through transcriptional activation of the mTOR inhibitor DDIT4. Determined the relationship between FTO alpha-ketoglutarate dependent dioxygenase (FTO), YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), and ATF4. Serine/threonine-protein kinase mTOR (MTOR) transcriptionally upregulated DDIT4 to suppress mTOR, which induced pro-survival autophagy during glutaminolysis inhibition." M6ADIS0059 39888307; 34373753 M6ADRUG0073 M6ACROT03441 REG00001 M6ATAR00339 Histone modification / Acetylation EPIREG00067 EPITAR00203 EPITAR00179 . Histone modification Direct Inhibition m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "HDACi reduces ferroptosis suppressor protein (FSP1) by promoting its mRNA degradation. Specifically, it is confirmed that HDACi specifically targets HDAC1 and promotes the Histone H3 lysine 27 acetylation (H3K27ac) modification of fat mass- and obesity-associated gene (FTO) and AlkB Homolog 5, RNA Demethylase (ALKBH5), which results in significant activation of FTO and ALKBH5. The activation of FTO and ALKBH5 reduces N6-methyladenosine (m6A) modification on FSP1 mRNA, leading to its degradation. Crucially, lactylation of HDAC1K412is essential for ferroptosis regulation. Both Vorinostat (SAHA) and Trichostatin A (TSA) notably diminish HDAC1K412lactylation in comparison to other HDAC1 inhibitors, exhibiting a consistent trend of increasing susceptibility to ferroptosis. In colorectal cancer, Glutaminolysis inhibition upregulated ATF4 expression in an m6A-dependent manner to activate pro-survival autophagy through transcriptional activation of the mTOR inhibitor DDIT4. Determined the relationship between FTO alpha-ketoglutarate dependent dioxygenase (FTO), YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), and ATF4. Serine/threonine-protein kinase mTOR (MTOR) transcriptionally upregulated DDIT4 to suppress mTOR, which induced pro-survival autophagy during glutaminolysis inhibition." M6ADIS0059 39888307; 34373753 M6ADRUG0063 M6ACROT03442 REG00001 M6ATAR00339 Histone modification / Acetylation EPIREG00067 EPITAR00203 EPITAR00179 . Histone modification Direct Inhibition m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "HDACi reduces ferroptosis suppressor protein (FSP1) by promoting its mRNA degradation. Specifically, it is confirmed that HDACi specifically targets HDAC1 and promotes the Histone H3 lysine 27 acetylation (H3K27ac) modification of fat mass- and obesity-associated gene (FTO) and AlkB Homolog 5, RNA Demethylase (ALKBH5), which results in significant activation of FTO and ALKBH5. The activation of FTO and ALKBH5 reduces N6-methyladenosine (m6A) modification on FSP1 mRNA, leading to its degradation. Crucially, lactylation of HDAC1K412is essential for ferroptosis regulation. Both Vorinostat (SAHA) and Trichostatin A (TSA) notably diminish HDAC1K412lactylation in comparison to other HDAC1 inhibitors, exhibiting a consistent trend of increasing susceptibility to ferroptosis. In colorectal cancer, Glutaminolysis inhibition upregulated ATF4 expression in an m6A-dependent manner to activate pro-survival autophagy through transcriptional activation of the mTOR inhibitor DDIT4. Determined the relationship between FTO alpha-ketoglutarate dependent dioxygenase (FTO), YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), and ATF4. ATF4 transcriptionally upregulated DDIT4 to suppress Serine/threonine-protein kinase mTOR (MTOR), which induced pro-survival autophagy during glutaminolysis inhibition." M6ADIS0059 39888307; 34373753 M6ADRUG0003 M6ACROT03443 REG00001 M6ATAR00339 Histone modification / Acetylation EPIREG00067 EPITAR00203 EPITAR00179 . Histone modification Direct Inhibition m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "HDACi reduces ferroptosis suppressor protein (FSP1) by promoting its mRNA degradation. Specifically, it is confirmed that HDACi specifically targets HDAC1 and promotes the Histone H3 lysine 27 acetylation (H3K27ac) modification of fat mass- and obesity-associated gene (FTO) and AlkB Homolog 5, RNA Demethylase (ALKBH5), which results in significant activation of FTO and ALKBH5. The activation of FTO and ALKBH5 reduces N6-methyladenosine (m6A) modification on FSP1 mRNA, leading to its degradation. Crucially, lactylation of HDAC1K412is essential for ferroptosis regulation. Both Vorinostat (SAHA) and Trichostatin A (TSA) notably diminish HDAC1K412lactylation in comparison to other HDAC1 inhibitors, exhibiting a consistent trend of increasing susceptibility to ferroptosis. In colorectal cancer, Glutaminolysis inhibition upregulated ATF4 expression in an m6A-dependent manner to activate pro-survival autophagy through transcriptional activation of the mTOR inhibitor DDIT4. Determined the relationship between FTO alpha-ketoglutarate dependent dioxygenase (FTO), YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), and ATF4. ATF4 transcriptionally upregulated DDIT4 to suppress Serine/threonine-protein kinase mTOR (MTOR), which induced pro-survival autophagy during glutaminolysis inhibition." M6ADIS0059 39888307; 34373753 M6ADRUG0064 M6ACROT03444 REG00001 M6ATAR00764 Histone modification / Acetylation EPIREG00067 EPITAR00203 EPITAR00179 Up regulation Histone modification Direct Inhibition m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "HDACi reduces ferroptosis suppressor protein (FSP1) by promoting its mRNA degradation. Specifically, it is confirmed that HDACi specifically targets HDAC1 and promotes the Histone H3 lysine 27 acetylation (H3K27ac) modification of fat mass- and obesity-associated gene (FTO) and AlkB Homolog 5, RNA Demethylase (ALKBH5), which results in significant activation of FTO and ALKBH5. The activation of FTO and ALKBH5 reduces N6-methyladenosine (m6A) modification on FSP1 mRNA, leading to its degradation. Crucially, lactylation of HDAC1K412is essential for ferroptosis regulation. Both Vorinostat (SAHA) and Trichostatin A (TSA) notably diminish HDAC1K412lactylation in comparison to other HDAC1 inhibitors, exhibiting a consistent trend of increasing susceptibility to ferroptosis. Targeting FTO significantly suppresses cancer cell growth and enhances chemotherapy sensitivity, which not only mediating the balance of intracellular ROS by regulating Glucose-6-phosphate dehydrogenase (G6PD) expression, but also maintaining genome instability by regulating PARP1 expression. These findings shed light on new molecular mechanisms of CRC development and treatments mediated by m6A modification." M6ADIS0059 39888307; 35297218 . M6ACROT03445 REG00001 M6ATAR00551 Histone modification / Acetylation EPIREG00067 EPITAR00203 EPITAR00179 Up regulation Histone modification Direct Inhibition m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "HDACi reduces ferroptosis suppressor protein (FSP1) by promoting its mRNA degradation. Specifically, it is confirmed that HDACi specifically targets HDAC1 and promotes the Histone H3 lysine 27 acetylation (H3K27ac) modification of fat mass- and obesity-associated gene (FTO) and AlkB Homolog 5, RNA Demethylase (ALKBH5), which results in significant activation of FTO and ALKBH5. The activation of FTO and ALKBH5 reduces N6-methyladenosine (m6A) modification on FSP1 mRNA, leading to its degradation. Crucially, lactylation of HDAC1K412is essential for ferroptosis regulation. Both Vorinostat (SAHA) and Trichostatin A (TSA) notably diminish HDAC1K412lactylation in comparison to other HDAC1 inhibitors, exhibiting a consistent trend of increasing susceptibility to ferroptosis. Targeting FTO significantly suppresses cancer cell growth and enhances chemotherapy sensitivity, which not only mediating the balance of intracellular ROS by regulating G6PD expression, but also maintaining genome instability by regulating Poly [ADP-ribose] polymerase 1 (PARP1) expression. These findings shed light on new molecular mechanisms of CRC development and treatments mediated by m6A modification." M6ADIS0059 39888307; 35297218 . M6ACROT03446 REG00001 M6ATAR00343 Histone modification / Acetylation EPIREG00067 EPITAR00203 EPITAR00179 Down regulation Histone modification Direct Inhibition m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "HDACi reduces ferroptosis suppressor protein (FSP1) by promoting its mRNA degradation. Specifically, it is confirmed that HDACi specifically targets HDAC1 and promotes the Histone H3 lysine 27 acetylation (H3K27ac) modification of fat mass- and obesity-associated gene (FTO) and AlkB Homolog 5, RNA Demethylase (ALKBH5), which results in significant activation of FTO and ALKBH5. The activation of FTO and ALKBH5 reduces N6-methyladenosine (m6A) modification on FSP1 mRNA, leading to its degradation. Crucially, lactylation of HDAC1K412is essential for ferroptosis regulation. Both Vorinostat (SAHA) and Trichostatin A (TSA) notably diminish HDAC1K412lactylation in comparison to other HDAC1 inhibitors, exhibiting a consistent trend of increasing susceptibility to ferroptosis. GSK3beta inhibited Myeloid zinc finger 1 (MZF1) expression by mediating FTO-regulated m6A modification of MZF1 and then decreased the proto-oncogene c-Myc expression, thus hampering CRC cell proliferation. " M6ADIS0059 39888307; 33533172 . M6ACROT03447 REG00001 M6ATAR00341 Histone modification / Acetylation EPIREG00067 EPITAR00203 EPITAR00179 Down regulation Histone modification Direct Inhibition m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "HDACi reduces ferroptosis suppressor protein (FSP1) by promoting its mRNA degradation. Specifically, it is confirmed that HDACi specifically targets HDAC1 and promotes the Histone H3 lysine 27 acetylation (H3K27ac) modification of fat mass- and obesity-associated gene (FTO) and AlkB Homolog 5, RNA Demethylase (ALKBH5), which results in significant activation of FTO and ALKBH5. The activation of FTO and ALKBH5 reduces N6-methyladenosine (m6A) modification on FSP1 mRNA, leading to its degradation. Crucially, lactylation of HDAC1K412is essential for ferroptosis regulation. Both Vorinostat (SAHA) and Trichostatin A (TSA) notably diminish HDAC1K412lactylation in comparison to other HDAC1 inhibitors, exhibiting a consistent trend of increasing susceptibility to ferroptosis. GSK3beta inhibited MZF1 expression by mediating FTO-regulated m6A modification of MZF1 and then decreased the proto-oncogene Myc proto-oncogene protein (MYC) expression, thus hampering CRC cell proliferation. " M6ADIS0059 39888307; 33533172 . M6ACROT03448 REG00001 M6ATAR00542 Histone modification / Acetylation EPIREG00067 EPITAR00203 EPITAR00179 Down regulation Histone modification Direct Inhibition m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "HDACi reduces ferroptosis suppressor protein (FSP1) by promoting its mRNA degradation. Specifically, it is confirmed that HDACi specifically targets HDAC1 and promotes the Histone H3 lysine 27 acetylation (H3K27ac) modification of fat mass- and obesity-associated gene (FTO) and AlkB Homolog 5, RNA Demethylase (ALKBH5), which results in significant activation of FTO and ALKBH5. The activation of FTO and ALKBH5 reduces N6-methyladenosine (m6A) modification on FSP1 mRNA, leading to its degradation. Crucially, lactylation of HDAC1K412is essential for ferroptosis regulation. Both Vorinostat (SAHA) and Trichostatin A (TSA) notably diminish HDAC1K412lactylation in comparison to other HDAC1 inhibitors, exhibiting a consistent trend of increasing susceptibility to ferroptosis. FTO inhibited CRC metastasis both in vitro and in vivo. FTO exerted a tumor suppressive role by inhibiting Metastasis-associated protein MTA1 (MTA1) expression in an m6A-dependent manner. Methylated MTA1 transcripts were recognized by an m6A ""reader"", insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2), which then stabilized its mRNA." M6ADIS0059 39888307; 34218271 . M6ACROT03449 REG00001 M6ATAR01454 Histone modification / Acetylation EPIREG00067 EPITAR00203 EPITAR00179 Up regulation Histone modification Direct Inhibition m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "HDACi reduces ferroptosis suppressor protein (FSP1) by promoting its mRNA degradation. Specifically, it is confirmed that HDACi specifically targets HDAC1 and promotes the Histone H3 lysine 27 acetylation (H3K27ac) modification of fat mass- and obesity-associated gene (FTO) and AlkB Homolog 5, RNA Demethylase (ALKBH5), which results in significant activation of FTO and ALKBH5. The activation of FTO and ALKBH5 reduces N6-methyladenosine (m6A) modification on FSP1 mRNA, leading to its degradation. Crucially, lactylation of HDAC1K412is essential for ferroptosis regulation. Both Vorinostat (SAHA) and Trichostatin A (TSA) notably diminish HDAC1K412lactylation in comparison to other HDAC1 inhibitors, exhibiting a consistent trend of increasing susceptibility to ferroptosis. Apoptosis regulatory protein Siva (SIVA1), a critical apoptotic gene, as a key downstream target of the FTO-mediated m6A demethylation. The m6A demethylation of SIVA1 at the CDS region induced its mRNA degradation via a YTHDF2-dependent mechanism.FTO inhibition may restore the sensitivity of chemo-resistant CRC cells to 5-FU." M6ADIS0059 39888307; 36307991 M6ADRUG0005 M6ACROT03450 REG00001 M6ATAR00283 Histone modification / Acetylation EPIREG00067 EPITAR00203 EPITAR00179 Down regulation Histone modification Direct Inhibition m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "HDACi reduces ferroptosis suppressor protein (FSP1) by promoting its mRNA degradation. Specifically, it is confirmed that HDACi specifically targets HDAC1 and promotes the Histone H3 lysine 27 acetylation (H3K27ac) modification of fat mass- and obesity-associated gene (FTO) and AlkB Homolog 5, RNA Demethylase (ALKBH5), which results in significant activation of FTO and ALKBH5. The activation of FTO and ALKBH5 reduces N6-methyladenosine (m6A) modification on FSP1 mRNA, leading to its degradation. Crucially, lactylation of HDAC1K412is essential for ferroptosis regulation. Both Vorinostat (SAHA) and Trichostatin A (TSA) notably diminish HDAC1K412lactylation in comparison to other HDAC1 inhibitors, exhibiting a consistent trend of increasing susceptibility to ferroptosis. this study revealed the FTO-ALKBH5/IGF2BP2/Hexokinase-2 (HK2)/FOXO1 axis as a mechanism of aberrant m6A modification and glycolysis regulation in CRC." M6ADIS0059 39888307; 37580808 . M6ACROT03451 REG00005 M6ATAR00140 Histone modification / Acetylation EPIREG00067 EPITAR00203 EPITAR00183 Up regulation Histone modification Direct Inhibition m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "HDACi reduces ferroptosis suppressor protein (FSP1) by promoting its mRNA degradation. Specifically, it is confirmed that HDACi specifically targets HDAC1 and promotes the Histone H3 lysine 27 acetylation (H3K27ac) modification of fat mass- and obesity-associated gene (FTO) and AlkB Homolog 5, RNA Demethylase (ALKBH5), which results in significant activation of FTO and ALKBH5. The activation of FTO and ALKBH5 reduces N6-methyladenosine (m6A) modification on FSP1 mRNA, leading to its degradation. Crucially, lactylation of HDAC1K412is essential for ferroptosis regulation. Both Vorinostat (SAHA) and Trichostatin A (TSA) notably diminish HDAC1K412lactylation in comparison to other HDAC1 inhibitors, exhibiting a consistent trend of increasing susceptibility to ferroptosis. ALKBH5 knockdown suppressed malignant behavior of colon cancer partially through Nuclear paraspeckle assembly transcript 1 (NEAT1) by demethylation in vitro and vivo, suggesting that ALKBH5-NEAT1 axis is a potential therapeutic target for colon cancer treatment." M6ADIS0059 39888307; 32913527 . M6ACROT03452 REG00005 M6ATAR00149 Histone modification / Acetylation EPIREG00067 EPITAR00203 EPITAR00183 Down regulation Histone modification Direct Inhibition m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "HDACi reduces ferroptosis suppressor protein (FSP1) by promoting its mRNA degradation. Specifically, it is confirmed that HDACi specifically targets HDAC1 and promotes the Histone H3 lysine 27 acetylation (H3K27ac) modification of fat mass- and obesity-associated gene (FTO) and AlkB Homolog 5, RNA Demethylase (ALKBH5), which results in significant activation of FTO and ALKBH5. The activation of FTO and ALKBH5 reduces N6-methyladenosine (m6A) modification on FSP1 mRNA, leading to its degradation. Crucially, lactylation of HDAC1K412is essential for ferroptosis regulation. Both Vorinostat (SAHA) and Trichostatin A (TSA) notably diminish HDAC1K412lactylation in comparison to other HDAC1 inhibitors, exhibiting a consistent trend of increasing susceptibility to ferroptosis. Overexpression of METTL3 upregulates Long intergenic non-protein coding RNA 2598 (LINC02598/RP11) expression in colorectal cancer cells. Overexpression of ALKBH5 downregulates RP11 expression." M6ADIS0059 39888307; 33335959 . M6ACROT03453 REG00005 M6ATAR00132 Histone modification / Acetylation EPIREG00067 EPITAR00203 EPITAR00183 . Histone modification Direct Inhibition m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "HDACi reduces ferroptosis suppressor protein (FSP1) by promoting its mRNA degradation. Specifically, it is confirmed that HDACi specifically targets HDAC1 and promotes the Histone H3 lysine 27 acetylation (H3K27ac) modification of fat mass- and obesity-associated gene (FTO) and AlkB Homolog 5, RNA Demethylase (ALKBH5), which results in significant activation of FTO and ALKBH5. The activation of FTO and ALKBH5 reduces N6-methyladenosine (m6A) modification on FSP1 mRNA, leading to its degradation. Crucially, lactylation of HDAC1K412is essential for ferroptosis regulation. Both Vorinostat (SAHA) and Trichostatin A (TSA) notably diminish HDAC1K412lactylation in comparison to other HDAC1 inhibitors, exhibiting a consistent trend of increasing susceptibility to ferroptosis. ALKBH5 plays an antitumor role in colorectal cancer by modulating the FOXO3/microRNA 21 (MIR21)/SPRY2 axis, which not only suggests a regulatory effect between ALKBH5 and FOXO3, but also provides a new therapeutic direction for colorectal cancer." M6ADIS0059 39888307; 34786052 . M6ACROT03454 REG00005 M6ATAR00260 Histone modification / Acetylation EPIREG00067 EPITAR00203 EPITAR00183 Down regulation Histone modification Direct Inhibition m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "HDACi reduces ferroptosis suppressor protein (FSP1) by promoting its mRNA degradation. Specifically, it is confirmed that HDACi specifically targets HDAC1 and promotes the Histone H3 lysine 27 acetylation (H3K27ac) modification of fat mass- and obesity-associated gene (FTO) and AlkB Homolog 5, RNA Demethylase (ALKBH5), which results in significant activation of FTO and ALKBH5. The activation of FTO and ALKBH5 reduces N6-methyladenosine (m6A) modification on FSP1 mRNA, leading to its degradation. Crucially, lactylation of HDAC1K412is essential for ferroptosis regulation. Both Vorinostat (SAHA) and Trichostatin A (TSA) notably diminish HDAC1K412lactylation in comparison to other HDAC1 inhibitors, exhibiting a consistent trend of increasing susceptibility to ferroptosis. ALKBH5 plays an antitumor role in colorectal cancer by modulating the Forkhead box protein O3 (FOXO3)/miR-21/SPRY2 axis, which not only suggests a regulatory effect between ALKBH5 and FOXO3, but also provides a new therapeutic direction for colorectal cancer." M6ADIS0059 39888307; 34786052 . M6ACROT03455 REG00005 M6ATAR00409 Histone modification / Acetylation EPIREG00067 EPITAR00203 EPITAR00183 Up regulation Histone modification Direct Inhibition m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "HDACi reduces ferroptosis suppressor protein (FSP1) by promoting its mRNA degradation. Specifically, it is confirmed that HDACi specifically targets HDAC1 and promotes the Histone H3 lysine 27 acetylation (H3K27ac) modification of fat mass- and obesity-associated gene (FTO) and AlkB Homolog 5, RNA Demethylase (ALKBH5), which results in significant activation of FTO and ALKBH5. The activation of FTO and ALKBH5 reduces N6-methyladenosine (m6A) modification on FSP1 mRNA, leading to its degradation. Crucially, lactylation of HDAC1K412is essential for ferroptosis regulation. Both Vorinostat (SAHA) and Trichostatin A (TSA) notably diminish HDAC1K412lactylation in comparison to other HDAC1 inhibitors, exhibiting a consistent trend of increasing susceptibility to ferroptosis. ALKBH5 plays an antitumor role in colorectal cancer by modulating the FOXO3/miR-21/Protein sprouty homolog 2 (SPRY2) axis, which not only suggests a regulatory effect between ALKBH5 and FOXO3, but also provides a new therapeutic direction for colorectal cancer." M6ADIS0059 39888307; 34786052 . M6ACROT03456 REG00005 M6ATAR00484 Histone modification / Acetylation EPIREG00067 EPITAR00203 EPITAR00183 Down regulation Histone modification Direct Inhibition m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "HDACi reduces ferroptosis suppressor protein (FSP1) by promoting its mRNA degradation. Specifically, it is confirmed that HDACi specifically targets HDAC1 and promotes the Histone H3 lysine 27 acetylation (H3K27ac) modification of fat mass- and obesity-associated gene (FTO) and AlkB Homolog 5, RNA Demethylase (ALKBH5), which results in significant activation of FTO and ALKBH5. The activation of FTO and ALKBH5 reduces N6-methyladenosine (m6A) modification on FSP1 mRNA, leading to its degradation. Crucially, lactylation of HDAC1K412is essential for ferroptosis regulation. Both Vorinostat (SAHA) and Trichostatin A (TSA) notably diminish HDAC1K412lactylation in comparison to other HDAC1 inhibitors, exhibiting a consistent trend of increasing susceptibility to ferroptosis. ALKBH5 was downregulated in CRC and ALKBH5 overexpression promoted ROS release and ferroptosis. ALKBH5 erased the m6A modification on Cystine/glutamate transporter (SLC7A11) mRNA to reduce the mRNA stability of SLC7A11, further reducing SLC7A11 expression. SLC7A11 overexpression reversed the promotive role of ALKBH5 overexpression in ferroptosis. ALKBH5 upregulation mitigated tumor growth in vivo." M6ADIS0059 39888307; 36820954 . M6ACROT03457 REG00005 M6ATAR00836 Histone modification / Acetylation EPIREG00067 EPITAR00203 EPITAR00183 Up regulation Histone modification Direct Inhibition m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "HDACi reduces ferroptosis suppressor protein (FSP1) by promoting its mRNA degradation. Specifically, it is confirmed that HDACi specifically targets HDAC1 and promotes the Histone H3 lysine 27 acetylation (H3K27ac) modification of fat mass- and obesity-associated gene (FTO) and AlkB Homolog 5, RNA Demethylase (ALKBH5), which results in significant activation of FTO and ALKBH5. The activation of FTO and ALKBH5 reduces N6-methyladenosine (m6A) modification on FSP1 mRNA, leading to its degradation. Crucially, lactylation of HDAC1K412is essential for ferroptosis regulation. Both Vorinostat (SAHA) and Trichostatin A (TSA) notably diminish HDAC1K412lactylation in comparison to other HDAC1 inhibitors, exhibiting a consistent trend of increasing susceptibility to ferroptosis. Tl increased the level of aberrant N6-methyladenosine (m6A) modification of Polyamine-transporting ATPase 13A3 (ATP13A3) via the METLL3/METTL14/ALKBH5-ATP13A5 axis to promote colorectal tumorigenesis." M6ADIS0059 39888307; 36745568 . M6ACROT03458 REG00005 M6ATAR00909 Histone modification / Acetylation EPIREG00067 EPITAR00203 EPITAR00183 Up regulation Histone modification Direct Inhibition m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "HDACi reduces ferroptosis suppressor protein (FSP1) by promoting its mRNA degradation. Specifically, it is confirmed that HDACi specifically targets HDAC1 and promotes the Histone H3 lysine 27 acetylation (H3K27ac) modification of fat mass- and obesity-associated gene (FTO) and AlkB Homolog 5, RNA Demethylase (ALKBH5), which results in significant activation of FTO and ALKBH5. The activation of FTO and ALKBH5 reduces N6-methyladenosine (m6A) modification on FSP1 mRNA, leading to its degradation. Crucially, lactylation of HDAC1K412is essential for ferroptosis regulation. Both Vorinostat (SAHA) and Trichostatin A (TSA) notably diminish HDAC1K412lactylation in comparison to other HDAC1 inhibitors, exhibiting a consistent trend of increasing susceptibility to ferroptosis. ALKBH5/YTHDF2-mediated m6A modification of Circ_AFF2 enhances radiosensitivity of colorectal cancer by inhibiting Cullin neddylation" M6ADIS0059 39888307; 37381158 . M6ACROT03459 REG00005 M6ATAR00917 Histone modification / Acetylation EPIREG00067 EPITAR00203 EPITAR00183 Up regulation Histone modification Direct Inhibition m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "HDACi reduces ferroptosis suppressor protein (FSP1) by promoting its mRNA degradation. Specifically, it is confirmed that HDACi specifically targets HDAC1 and promotes the Histone H3 lysine 27 acetylation (H3K27ac) modification of fat mass- and obesity-associated gene (FTO) and AlkB Homolog 5, RNA Demethylase (ALKBH5), which results in significant activation of FTO and ALKBH5. The activation of FTO and ALKBH5 reduces N6-methyladenosine (m6A) modification on FSP1 mRNA, leading to its degradation. Crucially, lactylation of HDAC1K412is essential for ferroptosis regulation. Both Vorinostat (SAHA) and Trichostatin A (TSA) notably diminish HDAC1K412lactylation in comparison to other HDAC1 inhibitors, exhibiting a consistent trend of increasing susceptibility to ferroptosis. Mechanistically, Ras-related protein Rab-5A (RAB5A) was identified as the downstream target of ALKBH5 in CRC development, and ALKBH5 posttranscriptionally activated RAB5A by m6A demethylation, which impeded the YTHDF2-mediated degradation of RAB5A mRNA. In addition, we demonstrated that dysregulation of the ALKBH5-RAB5A axis could affect the tumourigenicity of CRC." M6ADIS0059 39888307; 37203239 . M6ACROT03460 REG00005 M6ATAR00283 Histone modification / Acetylation EPIREG00067 EPITAR00203 EPITAR00183 Down regulation Histone modification Direct Inhibition m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "HDACi reduces ferroptosis suppressor protein (FSP1) by promoting its mRNA degradation. Specifically, it is confirmed that HDACi specifically targets HDAC1 and promotes the Histone H3 lysine 27 acetylation (H3K27ac) modification of fat mass- and obesity-associated gene (FTO) and AlkB Homolog 5, RNA Demethylase (ALKBH5), which results in significant activation of FTO and ALKBH5. The activation of FTO and ALKBH5 reduces N6-methyladenosine (m6A) modification on FSP1 mRNA, leading to its degradation. Crucially, lactylation of HDAC1K412is essential for ferroptosis regulation. Both Vorinostat (SAHA) and Trichostatin A (TSA) notably diminish HDAC1K412lactylation in comparison to other HDAC1 inhibitors, exhibiting a consistent trend of increasing susceptibility to ferroptosis. This study revealed the FTO-ALKBH5/IGF2BP2/Hexokinase-2 (HK2)/FOXO1 axis as a mechanism of aberrant m6A modification and glycolysis regulation in CRC." M6ADIS0059 39888307; 37580808 . M6ACROT03461 REG00005 M6ATAR00994 Histone modification / Acetylation EPIREG00067 EPITAR00203 EPITAR00183 . Histone modification Direct Inhibition m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "HDACi reduces ferroptosis suppressor protein (FSP1) by promoting its mRNA degradation. Specifically, it is confirmed that HDACi specifically targets HDAC1 and promotes the Histone H3 lysine 27 acetylation (H3K27ac) modification of fat mass- and obesity-associated gene (FTO) and AlkB Homolog 5, RNA Demethylase (ALKBH5), which results in significant activation of FTO and ALKBH5. The activation of FTO and ALKBH5 reduces N6-methyladenosine (m6A) modification on FSP1 mRNA, leading to its degradation. Crucially, lactylation of HDAC1K412is essential for ferroptosis regulation. Both Vorinostat (SAHA) and Trichostatin A (TSA) notably diminish HDAC1K412lactylation in comparison to other HDAC1 inhibitors, exhibiting a consistent trend of increasing susceptibility to ferroptosis. The rs11245997 A allele facilitated BET1-like protein (BET1L) expression by disrupting miR-140-3p binding. It also reduced BET1L m6A modification, which upregulated BET1L expression levels through a mechanism mediated by the m6A methyltransferases (METTL14 and WTAP) and the m6A demethylase ALKBH5." M6ADIS0059 39888307; 37115853 . M6ACROT03462 REG00005 M6ATAR01012 Histone modification / Acetylation EPIREG00067 EPITAR00203 EPITAR00183 . Histone modification Direct Inhibition m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "HDACi reduces ferroptosis suppressor protein (FSP1) by promoting its mRNA degradation. Specifically, it is confirmed that HDACi specifically targets HDAC1 and promotes the Histone H3 lysine 27 acetylation (H3K27ac) modification of fat mass- and obesity-associated gene (FTO) and AlkB Homolog 5, RNA Demethylase (ALKBH5), which results in significant activation of FTO and ALKBH5. The activation of FTO and ALKBH5 reduces N6-methyladenosine (m6A) modification on FSP1 mRNA, leading to its degradation. Crucially, lactylation of HDAC1K412is essential for ferroptosis regulation. Both Vorinostat (SAHA) and Trichostatin A (TSA) notably diminish HDAC1K412lactylation in comparison to other HDAC1 inhibitors, exhibiting a consistent trend of increasing susceptibility to ferroptosis. METTL14/ALKBH5/IGF2BPs combine to modulate JmjC domain-containing protein 8 (JMJD8) stability in an m6A-dependent manner, which increases glycolysis and accelerates the development of CRC by enhancing the enzymatic activity of PKM2." M6ADIS0059 39888307; 37310898 . M6ACROT03463 REG00005 M6ATAR00356 Histone modification / Acetylation EPIREG00067 EPITAR00203 EPITAR00183 Up regulation Histone modification Direct Inhibition m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "HDACi reduces ferroptosis suppressor protein (FSP1) by promoting its mRNA degradation. Specifically, it is confirmed that HDACi specifically targets HDAC1 and promotes the Histone H3 lysine 27 acetylation (H3K27ac) modification of fat mass- and obesity-associated gene (FTO) and AlkB Homolog 5, RNA Demethylase (ALKBH5), which results in significant activation of FTO and ALKBH5. The activation of FTO and ALKBH5 reduces N6-methyladenosine (m6A) modification on FSP1 mRNA, leading to its degradation. Crucially, lactylation of HDAC1K412is essential for ferroptosis regulation. Both Vorinostat (SAHA) and Trichostatin A (TSA) notably diminish HDAC1K412lactylation in comparison to other HDAC1 inhibitors, exhibiting a consistent trend of increasing susceptibility to ferroptosis. The interplay between CARMN and ALKBH5 promoted tumourigenesis in colorectal cancer patients via the Cellular tumor antigen p53 (TP53/p53)/ALKBH5/CARMN/miR-5683 pathway. These findings illuminate the role of m6A methylation in colorectal cancer patients with p53R273H mutation." M6ADIS0059 39888307; 39039912 . M6ACROT03464 REG00012 M6ATAR01012 Histone modification / Acetylation EPIREG00067 EPITAR00203 EPITAR00179 . Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "HDACi reduces ferroptosis suppressor protein (FSP1) by promoting its mRNA degradation. Specifically, it is confirmed that HDACi specifically targets HDAC1 and promotes the Histone H3 lysine 27 acetylation (H3K27ac) modification of fat mass- and obesity-associated gene (FTO) and AlkB Homolog 5, RNA Demethylase (ALKBH5), which results in significant activation of FTO and ALKBH5. The activation of FTO and ALKBH5 reduces N6-methyladenosine (m6A) modification on FSP1 mRNA, leading to its degradation. Crucially, lactylation of HDAC1K412is essential for ferroptosis regulation. Both Vorinostat (SAHA) and Trichostatin A (TSA) notably diminish HDAC1K412lactylation in comparison to other HDAC1 inhibitors, exhibiting a consistent trend of increasing susceptibility to ferroptosis. METTL14/ALKBH5/IGF2BP1 combine to modulate JmjC domain-containing protein 8 (JMJD8) stability in an m6A-dependent manner, which increases glycolysis and accelerates the development of CRC by enhancing the enzymatic activity of PKM2." M6ADIS0059 39888307; 37310898 . M6ACROT03465 REG00013 M6ATAR00445 Histone modification / Methylation EPIREG00044 EPITAR00204 EPITAR00028 Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator This feeds back upon the IGF2BP2 promoter region by further increasing SETD1A-mediated Histone H3 lysine 4 trimethylation (H3K4me3) level to upregulate IGF2BP2 expression. We demonstrated that this positive feedback loop between IGF2BP2 and SLC7A5 promotes lung cancer radioresistance through the AKT/mTOR pathway. Up-regulation of Vang-like protein 1 (VANGL1) by IGF2BP2 and miR-29b-3p attenuates the detrimental effect of irradiation on lung adenocarcinoma. Increased m6A level of VANGL1 and reduced miR-29b-3p took the responsibility of VANGL1 overexpression upon irradiation. M6ADIS0007 38281999; 33228740 . M6ACROT03466 REG00013 M6ATAR00147 Histone modification / Methylation EPIREG00044 EPITAR00204 EPITAR00028 Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "This feeds back upon the IGF2BP2 promoter region by further increasing SETD1A-mediated Histone H3 lysine 4 trimethylation (H3K4me3) level to upregulate IGF2BP2 expression. We demonstrated that this positive feedback loop between IGF2BP2 and SLC7A5 promotes lung cancer radioresistance through the AKT/mTOR pathway. HLA complex group 11 (HCG11) mediated by METTL14 inhibited the growth of lung adenocarcinoma via IGF2BP2/LATS1. The m6A modification of HCG11 promoted its nuclear exportation and binding by Insulin Like Growth Factor 2 MRNA Binding Protein 2 (IGF2BP2), resulting in increased stability." M6ADIS0007 38281999; 34624573 . M6ACROT03467 REG00013 M6ATAR00308 Histone modification / Methylation EPIREG00044 EPITAR00204 EPITAR00028 Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "This feeds back upon the IGF2BP2 promoter region by further increasing SETD1A-mediated Histone H3 lysine 4 trimethylation (H3K4me3) level to upregulate IGF2BP2 expression. We demonstrated that this positive feedback loop between IGF2BP2 and SLC7A5 promotes lung cancer radioresistance through the AKT/mTOR pathway. In lung cancer, IGF2BP2 modified m6A to increase the expression of Thymidine kinase, cytosolic (TK1), thus promoting angiogenesis." M6ADIS0007 38281999; 33758932 . M6ACROT03468 REG00013 M6ATAR00848 Histone modification / Methylation EPIREG00044 EPITAR00204 EPITAR00028 Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator This feeds back upon the IGF2BP2 promoter region by further increasing SETD1A-mediated Histone H3 lysine 4 trimethylation (H3K4me3) level to upregulate IGF2BP2 expression. We demonstrated that this positive feedback loop between IGF2BP2 and SLC7A5 promotes lung cancer radioresistance through the AKT/mTOR pathway. Silencing AC026356.1 significantly inhibited proliferation and migration but increased apoptosis in A549-cisplatin (DDP) cells.METTL14/IGF2BP2-mediated m6A modification and stabilization of the AC026356.1 RNA. M6ADIS0007 38281999; 37142269 . M6ACROT03469 REG00005 M6ATAR00140 Histone modification / Acetylation EPIREG00035 EPITAR00203 EPITAR00478 Up regulation Histone modification Indirect Enhancement m6A Histone modification indirectly regulates m6A modification through downstream signaling pathways Histone acetylation causes HSPA4 upregulation in GC tumor tissues. HSPA4 upregulation increases the protein stability of m6A demethylase ALKBH5. ALKBH5 decreases CD58 in GC cells through m6A methylation regulation. p300/CREBBP-mediated Histone H3 lysine 27 acetylation (H3K27ac) modification plays an important role in HSPA4 overexpression in GC tissues. ALKBH5 promotes Gastric cancer invasion and metastasis by demethylating the lncRNA Nuclear paraspeckle assembly transcript 1 (NEAT1). M6ADIS0057 38589927; 31290116 . M6ACROT03470 REG00005 M6ATAR00732 Histone modification / Acetylation EPIREG00035 EPITAR00203 EPITAR00478 Down regulation Histone modification Indirect Enhancement m6A Histone modification indirectly regulates m6A modification through downstream signaling pathways "Histone acetylation causes HSPA4 upregulation in GC tumor tissues. HSPA4 upregulation increases the protein stability of m6A demethylase ALKBH5. ALKBH5 decreases CD58 in GC cells through m6A methylation regulation. p300/CREBBP-mediated Histone H3 lysine 27 acetylation (H3K27ac) modification plays an important role in HSPA4 overexpression in GC tissues.Myt1 kinase (PKMYT1), as a downstream target of ALKBH5, promoted invasion and migration in GC. Moreover IGF2BP3 helped stabilize the mRNA stability of PKMYT1 via its m6A modification site." M6ADIS0057 38589927; 35114989 . M6ACROT03471 REG00005 M6ATAR00635 Histone modification / Acetylation EPIREG00035 EPITAR00203 EPITAR00478 Down regulation Histone modification Indirect Enhancement m6A Histone modification indirectly regulates m6A modification through downstream signaling pathways "Histone acetylation causes HSPA4 upregulation in GC tumor tissues. HSPA4 upregulation increases the protein stability of m6A demethylase ALKBH5. ALKBH5 decreases CD58 in GC cells through m6A methylation regulation. p300/CREBBP-mediated Histone H3 lysine 27 acetylation (H3K27ac) modification plays an important role in HSPA4 overexpression in GC tissues. Transcriptional repressor protein YY1 (YY1) was regulated by ALKBH5 and YTHDF1-mediated m6A modification and served as an autophagy-dependent tumor driver to accelerate cancer progression through ATG4B transactivation, providing an exploitable therapeutic target for GC." M6ADIS0057 38589927; 37724907 . M6ACROT03472 REG00005 M6ATAR00997 Histone modification / Acetylation EPIREG00035 EPITAR00203 EPITAR00478 Down regulation Histone modification Indirect Enhancement m6A Histone modification indirectly regulates m6A modification through downstream signaling pathways Histone acetylation causes HSPA4 upregulation in GC tumor tissues. HSPA4 upregulation increases the protein stability of m6A demethylase ALKBH5. ALKBH5 decreases CD58 in GC cells through m6A methylation regulation. p300/CREBBP-mediated Histone H3 lysine 27 acetylation (H3K27ac) modification plays an important role in HSPA4 overexpression in GC tissues. ALKBH5-mediated Glutathione-specific gamma-glutamylcyclotransferase 1 (CHAC1) depletion promotes malignant progression and decreases cisplatin-induced oxidative stress in gastric cancer M6ADIS0057 38589927; 38007439 M6ADRUG0047 M6ACROT03473 REG00013 M6ATAR00224 Histone modification / Lactylation EPIREG00035 EPITAR00208 EPITAR00028 Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "CTCF interacts with HNRNPU through a FLG-AS1-dependent mechanism, facilitating the recruitment of p300 and activation of the m6A reader IGF2BP2 by Histone H3 lysine 18 lactylation (H3K18la). This activation promotes histone lactylation at the promoter region of IGF2BP2 stimulating the proliferation of PDAC cells. IGF2BP2 enhanced the mRNA stability of CSF1 and MYC. IGF2BP2 functions in partnerships with Putative uncharacterized protein DANCR (DANCR) to regulate its stability. In tumor cells, IGF2BP2 is upregulated, which increases the chance of IGF2PB2 to interact with and stabilize DANCR.DANCR is a novel target for IGF2BP2 through m6A modification, and IGF2BP2 and DANCR work together to promote cancer stemness-like properties and pancreatic cancer pathogenesis." M6ADIS0061 39616247; 31804607 . M6ACROT03474 REG00013 M6ATAR00509 Histone modification / Lactylation EPIREG00035 EPITAR00208 EPITAR00028 Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "CTCF interacts with HNRNPU through a FLG-AS1-dependent mechanism, facilitating the recruitment of p300 and activation of the m6A reader IGF2BP2 by Histone H3 lysine 18 lactylation (H3K18la). This activation promotes histone lactylation at the promoter region of IGF2BP2 stimulating the proliferation of PDAC cells. IGF2BP2 enhanced the mRNA stability of CSF1 and MYC. PTGS2 antisense RNA 1 (PACERR) which bound to IGF2BP2 acts as an m6A-dependent manner to enhance the stability of KLF12 and c-myc in cytoplasm. This study found that LncRNA-PACERR functions as key regulator of TAMs in PDAC microenvironment and revealed the novel mechanisms in cytoplasm and in nucleus." M6ADIS0061 39616247; 35526050 . M6ACROT03475 REG00013 M6ATAR00510 Histone modification / Lactylation EPIREG00035 EPITAR00208 EPITAR00028 Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "CTCF interacts with HNRNPU through a FLG-AS1-dependent mechanism, facilitating the recruitment of p300 and activation of the m6A reader IGF2BP2 by Histone H3 lysine 18 lactylation (H3K18la). This activation promotes histone lactylation at the promoter region of IGF2BP2 stimulating the proliferation of PDAC cells. IGF2BP2 enhanced the mRNA stability of CSF1 and MYC. LncRNA-PACERR which bound to IGF2BP2 acts as an m6A-dependent manner to enhance the stability of Krueppel-like factor 12 (KLF12) and c-myc in cytoplasm. This study found that LncRNA-PACERR functions as key regulator of TAMs in PDAC microenvironment and revealed the novel mechanisms in cytoplasm and in nucleus." M6ADIS0061 39616247; 35526050 . M6ACROT03476 REG00013 M6ATAR00341 Histone modification / Lactylation EPIREG00035 EPITAR00208 EPITAR00028 Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "CTCF interacts with HNRNPU through a FLG-AS1-dependent mechanism, facilitating the recruitment of p300 and activation of the m6A reader IGF2BP2 by Histone H3 lysine 18 lactylation (H3K18la). This activation promotes histone lactylation at the promoter region of IGF2BP2 stimulating the proliferation of PDAC cells. IGF2BP2 enhanced the mRNA stability of CSF1 and MYC. LncRNA-PACERR which bound to IGF2BP2 acts as an m6A-dependent manner to enhance the stability of KLF12 and Myc proto-oncogene protein (MYC) in cytoplasm. This study found that LncRNA-PACERR functions as key regulator of TAMs in PDAC microenvironment and revealed the novel mechanisms in cytoplasm and in nucleus." M6ADIS0061 39616247; 35526050 . M6ACROT03477 REG00013 M6ATAR00341 Histone modification / Lactylation EPIREG00035 EPITAR00208 EPITAR00028 Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "CTCF interacts with HNRNPU through a FLG-AS1-dependent mechanism, facilitating the recruitment of p300 and activation of the m6A reader IGF2BP2 by Histone H3 lysine 18 lactylation (H3K18la). This activation promotes histone lactylation at the promoter region of IGF2BP2 stimulating the proliferation of PDAC cells. IGF2BP2 enhanced the mRNA stability of CSF1 and Myc proto-oncogene protein (MYC). YTHDF1 serves as a reader for the m6A modified LINC00901 and downregulates the LINC00901 level.LINC00901 positively regulates MYC through upregulation of IGF2BP2, a known RNA binding protein that can enhance MYC mRNA stability." M6ADIS0061 39616247; 37223505 . M6ACROT03478 REG00013 M6ATAR01442 Histone modification / Lactylation EPIREG00035 EPITAR00208 EPITAR00028 Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "CTCF interacts with HNRNPU through a FLG-AS1-dependent mechanism, facilitating the recruitment of p300 and activation of the m6A reader IGF2BP2 by Histone H3 lysine 18 lactylation (H3K18la). This activation promotes histone lactylation at the promoter region of IGF2BP2 stimulating the proliferation of PDAC cells. IGF2BP2 enhanced the mRNA stability of CSF1 and MYC. IGF2BP2 promotes pancreatic carcinoma progression by enhancing the stability of Beta-1,4-glucuronyltransferase 1 (B3GNT6) mRNA via m6A methylation" M6ADIS0061 39616247; 35908253 . M6ACROT03479 REG00013 M6ATAR00360 Histone modification / Lactylation EPIREG00035 EPITAR00208 EPITAR00028 Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "CTCF interacts with HNRNPU through a FLG-AS1-dependent mechanism, facilitating the recruitment of p300 and activation of the m6A reader IGF2BP2 by Histone H3 lysine 18 lactylation (H3K18la). This activation promotes histone lactylation at the promoter region of IGF2BP2 stimulating the proliferation of PDAC cells. IGF2BP2 enhanced the mRNA stability of CSF1 and MYC. Mechanistically, circMYO1C cyclization was mediated by m6A methyltransferase METTL3. Moreover, methylated RNA immunoprecipitation sequencing (MeRIP-seq) unveiled the remarkable m6A modification on Programmed cell death 1 ligand 1 (CD274/PD-L1) mRNA. Moreover, circMYO1C targeted the m6A site of PD-L1 mRNA to enhance its stability by cooperating with IGF2BP2, thereby accelerating PDAC immune escape." M6ADIS0061 39616247; 36781839 . M6ACROT03480 REG00013 M6ATAR01018 Histone modification / Lactylation EPIREG00035 EPITAR00208 EPITAR00028 Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "CTCF interacts with HNRNPU through a FLG-AS1-dependent mechanism, facilitating the recruitment of p300 and activation of the m6A reader IGF2BP2 by Histone H3 lysine 18 lactylation (H3K18la). This activation promotes histone lactylation at the promoter region of IGF2BP2 stimulating the proliferation of PDAC cells. IGF2BP2 enhanced the mRNA stability of CSF1 and MYC. METTL14 Facilitates the Metastasis of Pancreatic Carcinoma by Stabilizing Long intergenic non-protein coding RNA 941 (LINC00941) in an m6A-IGF2BP2-Dependent Manner" M6ADIS0061 39616247; 37215454 . M6ACROT03481 REG00007 M6ATAR01408 Histone modification / Lactylation EPIREG00051 EPITAR00220 EPITAR00027 . Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "LDHA-induced Histone H3 lysine 18 lactylation (H3K18lac) promoted NAFLD progression, where LDHA-induced H3K18lac in METTL3 promoter elevated METTL3 expression, thereby promoting m6A methylation and stabilizing SCD1 via a YTHDF1-dependent manner. Keywords: Nonalcoholic fatty liver disease, LDHA, METTL3, YTHDF1, Histone lactylation.Mechanistically, RPN11 deubiquitinates and stabilizes METTL3 to enhance the m6A modification and expression of acyl-coenzyme A (CoA) synthetase short-chain family member 3 (Acyl-CoA synthetase short-chain family member 3, mitochondrial (ACSS3)), which generates propionyl-CoA to upregulate lipid metabolism genes via histone propionylation. The RPN11-METTL3-ACSS3-histone propionylation pathway is activated in the livers of patients with NA" M6ADIS0107 39903889; 39146936 . M6ACROT03482 REG00022 M6ATAR00072 Histone modification / Lactylation EPIREG00035 EPITAR00208 EPITAR00238 Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "Histone H3 lysine 18 lactylation (H3K18la) in HCC induces increased expression of YTHDC1, increasing the stability of m6A-modified NEAT1. The histone acetyltransferase p300 is then recruited by NEAT1 and activates SCD by increasing the level of histone acetylation at the SCD promoter, thus facilitating HCC progression via hepatocellular lipid metabolism remodeling. Taken together, these discoveries suggest a close link between the epigenetic machinery and lipid metabolic abnormalities, which promotes cancer progression. hsa_circ_0092493 (circ_ARL3) is a critical regulator in HBV-related HCC, targeting the axis of circ-ARL3/miR-1305 can be a promising treatment for HBV+ HCC patients. HBx protein upregulated N6 -methyladenosine (m6A) methyltransferases METTL3 expression, increasing the m6A modification of circ-ARL3; then, m6A reader YTHDC1 bound to m6A-modified of circ-ARL3 and favored its reverse splicing and biogenesis. Furthermore, circ-ARL3 was able to sponge miR-1305, antagonizing the inhibitory effects of miR-1305 on a cohort of target oncogenes, thereby promoting HBV+ HCC progression. " M6ADIS0006 39725144; 33372396 . M6ACROT03483 REG00022 M6ATAR00058 Histone modification / Lactylation EPIREG00035 EPITAR00208 EPITAR00238 Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "Histone H3 lysine 18 lactylation (H3K18la) in HCC induces increased expression of YTHDC1, increasing the stability of m6A-modified NEAT1. The histone acetyltransferase p300 is then recruited by NEAT1 and activates SCD by increasing the level of histone acetylation at the SCD promoter, thus facilitating HCC progression via hepatocellular lipid metabolism remodeling. Taken together, these discoveries suggest a close link between the epigenetic machinery and lipid metabolic abnormalities, which promotes cancer progression. In hepatocellular carcinoma, METTL3 could direct the formation of circHPS5, and specific m6A controlled the accumulation of circHPS5. YTHDC1 facilitated the cytoplasmic output of hsa_circ_0021427 (circHPS5) under m6A modification. CircHPS5 can act as a miR-370 sponge to regulate the expression of HMGA2 and further accelerate hepatocellular carcinoma cell tumorigenesis." M6ADIS0006 39725144; 34703649 . M6ACROT03484 REG00022 M6ATAR00119 Histone modification / Lactylation EPIREG00035 EPITAR00208 EPITAR00238 . Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "Histone H3 lysine 18 lactylation (H3K18la) in HCC induces increased expression of YTHDC1, increasing the stability of m6A-modified NEAT1. The histone acetyltransferase p300 is then recruited by NEAT1 and activates SCD by increasing the level of histone acetylation at the SCD promoter, thus facilitating HCC progression via hepatocellular lipid metabolism remodeling. Taken together, these discoveries suggest a close link between the epigenetic machinery and lipid metabolic abnormalities, which promotes cancer progression. In hepatocellular carcinoma, METTL3 could direct the formation of circHPS5, and specific m6A controlled the accumulation of circHPS5. YTHDC1 facilitated the cytoplasmic output of circHPS5 under m6A modification. CircHPS5 can act as a microRNA 370 (MIR370) sponge to regulate the expression of HMGA2 and further accelerate hepatocellular carcinoma cell tumorigenesis." M6ADIS0006 39725144; 34703649 . M6ACROT03485 REG00022 M6ATAR00276 Histone modification / Lactylation EPIREG00035 EPITAR00208 EPITAR00238 Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "Histone H3 lysine 18 lactylation (H3K18la) in HCC induces increased expression of YTHDC1, increasing the stability of m6A-modified NEAT1. The histone acetyltransferase p300 is then recruited by NEAT1 and activates SCD by increasing the level of histone acetylation at the SCD promoter, thus facilitating HCC progression via hepatocellular lipid metabolism remodeling. Taken together, these discoveries suggest a close link between the epigenetic machinery and lipid metabolic abnormalities, which promotes cancer progression. In hepatocellular carcinoma, METTL3 could direct the formation of circHPS5, and specific m6A controlled the accumulation of circHPS5. YTHDC1 facilitated the cytoplasmic output of circHPS5 under m6A modification. CircHPS5 can act as a miR-370 sponge to regulate the expression of High mobility group protein HMGI-C (HMGA2) and further accelerate hepatocellular carcinoma cell tumorigenesis." M6ADIS0006 39725144; 34703649 . M6ACROT03486 REG00022 M6ATAR00069 Histone modification / Lactylation EPIREG00035 EPITAR00208 EPITAR00238 Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "Histone H3 lysine 18 lactylation (H3K18la) in HCC induces increased expression of YTHDC1, increasing the stability of m6A-modified NEAT1. The histone acetyltransferase p300 is then recruited by NEAT1 and activates SCD by increasing the level of histone acetylation at the SCD promoter, thus facilitating HCC progression via hepatocellular lipid metabolism remodeling. Taken together, these discoveries suggest a close link between the epigenetic machinery and lipid metabolic abnormalities, which promotes cancer progression. In hepatocellular carcinoma, hsa_circ_0058493 contained m6A methylation sites and that METTL3 mediated the degree of methylation modification of hsa_circ_0058493. YTHDC1 could bind to hsa_circ_0058493 and promote its intracellular localization from the nucleus to the cytoplasm." M6ADIS0006 39725144; 34888309 . M6ACROT03487 REG00022 M6ATAR00854 Histone modification / Lactylation EPIREG00035 EPITAR00208 EPITAR00238 Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "Histone H3 lysine 18 lactylation (H3K18la) in HCC induces increased expression of YTHDC1, increasing the stability of m6A-modified NEAT1. The histone acetyltransferase p300 is then recruited by NEAT1 and activates SCD by increasing the level of histone acetylation at the SCD promoter, thus facilitating HCC progression via hepatocellular lipid metabolism remodeling. Taken together, these discoveries suggest a close link between the epigenetic machinery and lipid metabolic abnormalities, which promotes cancer progression. m6A-modified Long non-coding RNA epigenetically activating Wnt/beta-catenin signalling in HCC (LEAWBIH) binds to the m6A reader YTHDC1, which further interacts with and recruits H3K9me2 demethylase KDM3B to CTNNB1 promoter, leading to H3K9me2 demethylation and CTNNB1 transcription activation. Functional rescue assays showed that blocking Wnt/beta-catenin signaling abolished the role of LEAWBIH in HCC." M6ADIS0006 39725144; 37954496 . M6ACROT03488 REG00022 M6ATAR00860 Histone modification / Lactylation EPIREG00035 EPITAR00208 EPITAR00238 Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "Histone H3 lysine 18 lactylation (H3K18la) in HCC induces increased expression of YTHDC1, increasing the stability of m6A-modified NEAT1. The histone acetyltransferase p300 is then recruited by NEAT1 and activates SCD by increasing the level of histone acetylation at the SCD promoter, thus facilitating HCC progression via hepatocellular lipid metabolism remodeling. Taken together, these discoveries suggest a close link between the epigenetic machinery and lipid metabolic abnormalities, which promotes cancer progression. m6A-modified ATP8B1 antisense RNA 1 (ATP8B1-AS1) interacts with and recruits m6A reader YTHDC1 and histone demethylase KDM3B to MYC promoter region, leading to the reduction of H3K9me2 level at MYC promoter region and activation of MYC transcription. Functional rescue assays showed that depletion of MYC largely abolished the oncogenic roles of ATP8B1-AS1." M6ADIS0006 39725144; 37701563 . M6ACROT03489 REG00022 M6ATAR00979 Histone modification / Lactylation EPIREG00035 EPITAR00208 EPITAR00238 Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "Histone H3 lysine 18 lactylation (H3K18la) in HCC induces increased expression of YTHDC1, increasing the stability of m6A-modified NEAT1. The histone acetyltransferase p300 is then recruited by NEAT1 and activates SCD by increasing the level of histone acetylation at the SCD promoter, thus facilitating HCC progression via hepatocellular lipid metabolism remodeling. Taken together, these discoveries suggest a close link between the epigenetic machinery and lipid metabolic abnormalities, which promotes cancer progression. The expression of FAM111A was positively correlated with the m6A level of FAM111A divergent transcript (FAM111A-DT), and the expression of methyltransferase complex, YTHDC1, and KDM3B in HCC tissues. Depletion of FAM111A largely attenuated the roles of m6A-modified FAM111A-DT in HCC. In summary, the m6A-modified FAM111A-DT/YTHDC1/KDM3B/FAM111A regulatory axis promoted HCC growth and represented a candidate therapeutic target for HCC." M6ADIS0006 39725144; 37400994 . M6ACROT03490 REG00022 M6ATAR01050 Histone modification / Lactylation EPIREG00035 EPITAR00208 EPITAR00238 Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "Histone H3 lysine 18 lactylation (H3K18la) in HCC induces increased expression of YTHDC1, increasing the stability of m6A-modified NEAT1. The histone acetyltransferase p300 is then recruited by NEAT1 and activates SCD by increasing the level of histone acetylation at the SCD promoter, thus facilitating HCC progression via hepatocellular lipid metabolism remodeling. Taken together, these discoveries suggest a close link between the epigenetic machinery and lipid metabolic abnormalities, which promotes cancer progression. METTL3/YTHDC1-mediated upregulation of Long intergenic non-protein coding RNA 294 (LINC00294) promotes hepatocellular carcinoma progression.LINC00294 promoted the interaction between YTHDC1 and HK2 and GLUT1 mRNA." M6ADIS0006 39725144; 38125436 . M6ACROT03491 REG00007 M6ATAR00814 Histone modification / Methylation EPIREG00074 EPITAR00202 EPITAR00027 Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "EHMT2 promotes m6A methyltransferase activity of METTL3 by regulating Histone H3 lysine 9 dimethylation (H3K9me2) level during ET. Protein SON rescues MYC and suppresses the METTL3-HSC inflammatory gene expression program, including CCL5, through transcriptional regulation. Thus, our findings define a m6A-SON-CCL5 axis that controls inflammation and HSC fate." M6ADIS0125 37858336; 38065069 . M6ACROT03492 REG00007 M6ATAR01502 Histone modification / Methylation EPIREG00074 EPITAR00202 EPITAR00027 . Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator EHMT2 promotes m6A methyltransferase activity of METTL3 by regulating Histone H3 lysine 9 dimethylation (H3K9me2) level during ET. Mettl3/Ythdf2 regulate macrophage inflammation and ROS generation by controlling Protein-tyrosine kinase 2-beta (PYK2) mRNA stability. M6ADIS0125 37858336; 37952687 . M6ACROT03493 REG00006 M6ATAR00534 Histone modification / Methylation EPIREG00056 EPITAR00225 EPITAR00195 . Histone modification Direct Inhibition m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "JMJD6 affects METTL14 expression in an arginine Histone H4 arginine 3 symmetric dimethylation (H4R3me2a) dependent manner, and mediates m6A modification of SLC3A2 to regulate its expression level, thereby affecting the sensitivity of lung cancer cells to ferroptosis.METTL14 was remarkably downregulated in LC tissues and cell lines. METTL14 mediated the maturation of hsa-miR-30c-1-3p." M6ADIS0007 40011892; 34586620 . M6ACROT03494 REG00006 M6ATAR00081 Histone modification / Lactylation . EPITAR00208 EPITAR00195 Up regulation Histone modification Direct Enhancement m6A Histone modification directly impacts m6A modification through modulating the level of m6A regulator "Histone H3 lysine 18 lactylation (H3K18la) was found to upregulate METTL14 expression. In conclusion, METTL14 knockdown promotes stemness in GC by mediating m6A modification of ATF5 mRNA, which activates the WDR74/beta-catenin axis, making METTL14 a potential therapeutic target for gastric cancer treatment. In gastric cancer, METTL14 was involved in the m6A modification of LINC01320 and induced the up-regulation of Long intergenic non-protein coding RNA 1320 (LINC01320)." M6ADIS0057 39497511; 34288797 . M6ACROT03495 REG00006 M6ATAR00616 Histone modification / Lactylation . EPITAR00208 EPITAR00195 Down regulation Histone modification Direct Enhancement m6A Histone modification directly impacts m6A modification through modulating the level of m6A regulator "Histone H3 lysine 18 lactylation (H3K18la) was found to upregulate METTL14 expression. In conclusion, METTL14 knockdown promotes stemness in GC by mediating m6A modification of ATF5 mRNA, which activates the WDR74/beta-catenin axis, making METTL14 a potential therapeutic target for gastric cancer treatment. METTL14-mediated m6A modification of Circ_ORC5 suppresses gastric cancer progression by regulating miR-30c-2-3p/AKT1S1 axis. METTL14 was downregulated in GC tissue samples and its low expression acted as a prognostic factor of poor survival in patients with GC." M6ADIS0057 39497511; 35164771 . M6ACROT03496 REG00006 M6ATAR00617 Histone modification / Lactylation . EPITAR00208 EPITAR00195 Up regulation Histone modification Direct Enhancement m6A Histone modification directly impacts m6A modification through modulating the level of m6A regulator "Histone H3 lysine 18 lactylation (H3K18la) was found to upregulate METTL14 expression. In conclusion, METTL14 knockdown promotes stemness in GC by mediating m6A modification of ATF5 mRNA, which activates the WDR74/beta-catenin axis, making METTL14 a potential therapeutic target for gastric cancer treatment. METTL14-mediated m6A modification of circORC5 suppresses gastric cancer progression by regulating hsa-miR-30c-2-3p/AKT1S1 axis.METTL14 was downregulated in GC tissue samples and its low expression acted as a prognostic factor of poor survival in patients with GC." M6ADIS0057 39497511; 35164771 . M6ACROT03497 REG00006 M6ATAR00618 Histone modification / Lactylation . EPITAR00208 EPITAR00195 Down regulation Histone modification Direct Enhancement m6A Histone modification directly impacts m6A modification through modulating the level of m6A regulator "Histone H3 lysine 18 lactylation (H3K18la) was found to upregulate METTL14 expression. In conclusion, METTL14 knockdown promotes stemness in GC by mediating m6A modification of ATF5 mRNA, which activates the WDR74/beta-catenin axis, making METTL14 a potential therapeutic target for gastric cancer treatment. METTL14-mediated m6A modification of circORC5 suppresses gastric cancer progression by regulating miR-30c-2-3p/Proline-rich AKT1 substrate 1 (AKT1S1) axis. METTL14 was downregulated in GC tissue samples and its low expression acted as a prognostic factor of poor survival in patients with GC." M6ADIS0057 39497511; 35164771 . M6ACROT03498 REG00006 M6ATAR00368 Histone modification / Lactylation . EPITAR00208 EPITAR00195 Down regulation Histone modification Direct Enhancement m6A Histone modification directly impacts m6A modification through modulating the level of m6A regulator "Histone H3 lysine 18 lactylation (H3K18la) was found to upregulate METTL14 expression. In conclusion, METTL14 knockdown promotes stemness in GC by mediating m6A modification of ATF5 mRNA, which activates the WDR74/beta-catenin axis, making METTL14 a potential therapeutic target for gastric cancer treatment. The m6A modification level was decreased in GC and METTL14 was a key regulator resulting in m6A disorder in GC. METTL14 overexpression suppressed GC cell proliferation and aggression by deactivating the PI3-kinase subunit alpha (PI3k/PIK3CA)/AKT/mTOR pathway and the EMT pathway, respectively." M6ADIS0057 39497511; 33314339 . M6ACROT03499 REG00006 M6ATAR00175 Histone modification / Lactylation . EPITAR00208 EPITAR00195 Down regulation Histone modification Direct Enhancement m6A Histone modification directly impacts m6A modification through modulating the level of m6A regulator "Histone H3 lysine 18 lactylation (H3K18la) was found to upregulate METTL14 expression. In conclusion, METTL14 knockdown promotes stemness in GC by mediating m6A modification of ATF5 mRNA, which activates the WDR74/beta-catenin axis, making METTL14 a potential therapeutic target for gastric cancer treatment. The m6A modification level was decreased in GC and METTL14 was a key regulator resulting in m6A disorder in GC. METTL14 overexpression suppressed GC cell proliferation and aggression by deactivating the PI3K/RAC-alpha serine/threonine-protein kinase (AKT1)/mTOR pathway and the EMT pathway, respectively." M6ADIS0057 39497511; 33314339 . M6ACROT03500 REG00006 M6ATAR00339 Histone modification / Lactylation . EPITAR00208 EPITAR00195 Down regulation Histone modification Direct Enhancement m6A Histone modification directly impacts m6A modification through modulating the level of m6A regulator "Histone H3 lysine 18 lactylation (H3K18la) was found to upregulate METTL14 expression. In conclusion, METTL14 knockdown promotes stemness in GC by mediating m6A modification of ATF5 mRNA, which activates the WDR74/beta-catenin axis, making METTL14 a potential therapeutic target for gastric cancer treatment. The m6A modification level was decreased in GC and METTL14 was a key regulator resulting in m6A disorder in GC. METTL14 overexpression suppressed GC cell proliferation and aggression by deactivating the PI3K/AKT/Serine/threonine-protein kinase mTOR (MTOR) pathway and the EMT pathway, respectively." M6ADIS0057 39497511; 33314339 . M6ACROT03501 REG00006 M6ATAR00375 Histone modification / Lactylation . EPITAR00208 EPITAR00195 Up regulation Histone modification Direct Enhancement m6A Histone modification directly impacts m6A modification through modulating the level of m6A regulator "Histone H3 lysine 18 lactylation (H3K18la) was found to upregulate METTL14 expression. In conclusion, METTL14 knockdown promotes stemness in GC by mediating m6A modification of ATF5 mRNA, which activates the WDR74/beta-catenin axis, making METTL14 a potential therapeutic target for gastric cancer treatment. METTL14 inhibits tumor growth and metastasis of Stomach Adenocarcinoma via stabilization of Mutated in multiple advanced cancers 1 (PTEN) mRNA expression. Therefore, METTL14 is a potential biomarker of prognosis and therapeutic targets for Stomach Adenocarcinoma." M6ADIS0057 39497511; 34476213 . M6ACROT03502 REG00006 M6ATAR00418 Histone modification / Lactylation . EPITAR00208 EPITAR00195 . Histone modification Direct Enhancement m6A Histone modification directly impacts m6A modification through modulating the level of m6A regulator "Histone H3 lysine 18 lactylation (H3K18la) was found to upregulate METTL14 expression. In conclusion, METTL14 knockdown promotes stemness in GC by mediating m6A modification of ATF5 mRNA, which activates the WDR74/beta-catenin axis, making METTL14 a potential therapeutic target for gastric cancer treatment. Mechanistically, AGAP2-AS1 bound WT1-associated protein (WTAP) to promote the formation of the WTAP/methyltransferase-like 3 (METTL3)/METTL14 m6A methyltransferase complex. AGAP2-AS1 stabilized signal transducer and activator of transcription 3 (Signal transducer and activator of transcription 3 (STAT3)) mRNA in an m6A-dependent manner and, thus, activated the interleukin 6 (IL6)/STAT3 pathway. Importantly, activation of the AGAP2-AS1/WTAP/STAT3 pathways promoted cell proliferation and migration in GC." M6ADIS0057 39497511; 37983949 . M6ACROT03503 REG00007 M6ATAR01443 Histone modification / Methylation EPIREG00039 EPITAR00204 EPITAR00027 . Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "KMT2A-mediated Histone H3 lysine 4 trimethylation (H3K4me3) regulates the autophagy-GATA4 axis through METTL3-mediated m6A modification of ATG4a to promote NPCs senescence and IVDD progression. METTL3 stabilized Toll-like receptor 2 (TLR2) mRNA in an IGF2BP1-dependent manner. METTL3 silencing restored specific gut microbiota levels in IDD rats, which was further reversed by administration of Pam3CSK4. These results demonstrate the beneficial effects of METTL3 silencing on NPC senescence and amelioration of IVD injury, involving modulation of TLR2 m6A modification and gut microbiota. These findings support METTL3 silencing as a potential therapeutic target for IDD." M6ADIS0168 39572532; 38853707 . M6ACROT03504 REG00007 M6ATAR00112 Histone modification / Acetylation EPIREG00035 EPITAR00203 EPITAR00027 . Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "The transcription factor ETS1 recruited p300 and WDR5 which separately mediated Histone H3 lysine 27 acetylation (H3K27ac) and H3K4me3 histone modification in the promoter of METTL3 and induced METTL3 transcription activation. Furthermore, we identified TXNDC5 as a target of METTL3-mediated m6A modification through MeRIP-seq, and revealed that METTL3-mediated TXNDC5 expression relied on the m6A reader-dependent manner. ZNFX1 antisense RNA 1 (ZFAS1) sequestered miR-647, and this RNA-RNA interaction is regulated by METLL3-mediated m6A modification in cervical cancer." M6ADIS0008 35987795; 33235466 . M6ACROT03505 REG00007 M6ATAR00094 Histone modification / Acetylation EPIREG00035 EPITAR00203 EPITAR00027 Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "The transcription factor ETS1 recruited p300 and WDR5 which separately mediated Histone H3 lysine 27 acetylation (H3K27ac) and H3K4me3 histone modification in the promoter of METTL3 and induced METTL3 transcription activation. Furthermore, we identified TXNDC5 as a target of METTL3-mediated m6A modification through MeRIP-seq, and revealed that METTL3-mediated TXNDC5 expression relied on the m6A reader-dependent manner. METTL3/FOXD2 adjacent opposite strand RNA 1 (FOXD2-AS1) accelerates cervical cancer progression via a m6A-dependent modality, which serves as a potential therapeutic target for cervical cancer." M6ADIS0008 35987795; 34589576 . M6ACROT03506 REG00007 M6ATAR00533 Histone modification / Acetylation EPIREG00035 EPITAR00203 EPITAR00027 Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "The transcription factor ETS1 recruited p300 and WDR5 which separately mediated Histone H3 lysine 27 acetylation (H3K27ac) and H3K4me3 histone modification in the promoter of METTL3 and induced METTL3 transcription activation. Furthermore, we identified TXNDC5 as a target of METTL3-mediated m6A modification through MeRIP-seq, and revealed that METTL3-mediated TXNDC5 expression relied on the m6A reader-dependent manner. METTL3 interacts with IGF2BP3 to promote the mRNA stability of Apoptotic chromatin condensation inducer in the nucleus (ACIN1), the overexpression of which induces the aggressiveness of CC cells." M6ADIS0008 35987795; 35255776 . M6ACROT03507 REG00007 M6ATAR00283 Histone modification / Acetylation EPIREG00035 EPITAR00203 EPITAR00027 Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "The transcription factor ETS1 recruited p300 and WDR5 which separately mediated Histone H3 lysine 27 acetylation (H3K27ac) and H3K4me3 histone modification in the promoter of METTL3 and induced METTL3 transcription activation. Furthermore, we identified TXNDC5 as a target of METTL3-mediated m6A modification through MeRIP-seq, and revealed that METTL3-mediated TXNDC5 expression relied on the m6A reader-dependent manner. METTL3 enhanced the Hexokinase-2 (HK2) stability through YTHDF1-mediated m6A modification, thereby promoting the Warburg effect of CC, which promotes a novel insight for the CC treatment." M6ADIS0008 35987795; 33099572 . M6ACROT03508 REG00007 M6ATAR00599 Histone modification / Acetylation EPIREG00035 EPITAR00203 EPITAR00027 Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "The transcription factor ETS1 recruited p300 and WDR5 which separately mediated Histone H3 lysine 27 acetylation (H3K27ac) and H3K4me3 histone modification in the promoter of METTL3 and induced METTL3 transcription activation. Furthermore, we identified TXNDC5 as a target of METTL3-mediated m6A modification through MeRIP-seq, and revealed that METTL3-mediated TXNDC5 expression relied on the m6A reader-dependent manner. METTL3 modulates miR-193b mature process in an m6A-dependent manner. Reintroduction of hsa-miR-193b profoundly inhibits tumorigenesis of cervical cancer cells both in vivo and in vitro through CCND1 targeting." M6ADIS0008 35987795; 34178650 . M6ACROT03509 REG00007 M6ATAR00206 Histone modification / Acetylation EPIREG00035 EPITAR00203 EPITAR00027 Down regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "The transcription factor ETS1 recruited p300 and WDR5 which separately mediated Histone H3 lysine 27 acetylation (H3K27ac) and H3K4me3 histone modification in the promoter of METTL3 and induced METTL3 transcription activation. Furthermore, we identified TXNDC5 as a target of METTL3-mediated m6A modification through MeRIP-seq, and revealed that METTL3-mediated TXNDC5 expression relied on the m6A reader-dependent manner. METTL3 modulates miR-193b mature process in an m6A-dependent manner. Reintroduction of miR-193b profoundly inhibits tumorigenesis of cervical cancer cells both in vivo and in vitro through G1/S-specific cyclin-D1 (CCND1) targeting." M6ADIS0008 35987795; 34178650 . M6ACROT03510 REG00007 M6ATAR00729 Histone modification / Acetylation EPIREG00035 EPITAR00203 EPITAR00027 . Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "The transcription factor ETS1 recruited p300 and WDR5 which separately mediated Histone H3 lysine 27 acetylation (H3K27ac) and H3K4me3 histone modification in the promoter of METTL3 and induced METTL3 transcription activation. Furthermore, we identified TXNDC5 as a target of METTL3-mediated m6A modification through MeRIP-seq, and revealed that METTL3-mediated TXNDC5 expression relied on the m6A reader-dependent manner. DARS-AS1 was validated to facilitate DARS translation via recruiting METTL3 and METTL14, which bound with DARS mRNA Aspartate--tRNA ligase, cytoplasmic (DARS) mRNA 5' untranslated region (5'UTR) and promoting its translation. The present study demonstrated that the 'HIF1-Alpha/DARS-AS1/DARS/ATG5/ATG3' pathway regulated the hypoxia-induced cytoprotective autophagy of cervical cancer(CC) and is a promising target of therapeutic strategies for patients afflicted with CC." M6ADIS0008 35987795; 35638109 . M6ACROT03511 REG00007 M6ATAR01450 Histone modification / Acetylation EPIREG00035 EPITAR00203 EPITAR00027 Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "The transcription factor ETS1 recruited p300 and WDR5 which separately mediated Histone H3 lysine 27 acetylation (H3K27ac) and H3K4me3 histone modification in the promoter of METTL3 and induced METTL3 transcription activation. Furthermore, we identified TXNDC5 as a target of METTL3-mediated m6A modification through MeRIP-seq, and revealed that METTL3-mediated TXNDC5 expression relied on the m6A reader-dependent manner. METTL3 mediated the m6A modification of cathepsin L (Procathepsin L (CTSL)) mRNA at the 5'-UTR, and the m6A reader protein insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) bound to the m6A sites and enhanced CTSL mRNA stability. Our results indicated that METTL3 enhanced CTSL mRNA stability through an m6A-IGF2BP2-dependent mechanism, thereby promoting cervical cancer cell metastasis." M6ADIS0008 35987795; 36382580 . M6ACROT03512 REG00007 M6ATAR00966 Histone modification / Acetylation EPIREG00035 EPITAR00203 EPITAR00027 Down regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "The transcription factor ETS1 recruited p300 and WDR5 which separately mediated Histone H3 lysine 27 acetylation (H3K27ac) and H3K4me3 histone modification in the promoter of METTL3 and induced METTL3 transcription activation. Furthermore, we identified TXNDC5 as a target of METTL3-mediated m6A modification through MeRIP-seq, and revealed that METTL3-mediated TXNDC5 expression relied on the m6A reader-dependent manner. METTL3/YTHDF2 promoted the degradation of Circ_RNF13 and subsequently affected the stability of CXC motif chemokine ligand 1 (CXCL1), ultimately enhancing the radiosensitivity of CC cells." M6ADIS0008 35987795; 37468464 . M6ACROT03513 REG00007 M6ATAR00980 Histone modification / Acetylation EPIREG00035 EPITAR00203 EPITAR00027 Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "The transcription factor ETS1 recruited p300 and WDR5 which separately mediated Histone H3 lysine 27 acetylation (H3K27ac) and H3K4me3 histone modification in the promoter of METTL3 and induced METTL3 transcription activation. Furthermore, we identified TXNDC5 as a target of METTL3-mediated m6A modification through MeRIP-seq, and revealed that METTL3-mediated TXNDC5 expression relied on the m6A reader-dependent manner. METIL3 is believed to enhance the expression of Long intergenic non-protein coding RNA 426 (LINC00426) through m6A methylation modification.The LINC00426/miR-200a-3p/ZEB1 axis plays a crucial role in regulating E-cadherin, N-cadherin and vimentin during EMT in CC.Overexpression of LINC00426 in CC cells caused resistance to Cisplatin and Bleomycin, but sensitivity to imatinib." M6ADIS0008 35987795; 37392859 M6ADRUG0047 M6ACROT03514 REG00007 M6ATAR00980 Histone modification / Acetylation EPIREG00035 EPITAR00203 EPITAR00027 Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "The transcription factor ETS1 recruited p300 and WDR5 which separately mediated Histone H3 lysine 27 acetylation (H3K27ac) and H3K4me3 histone modification in the promoter of METTL3 and induced METTL3 transcription activation. Furthermore, we identified TXNDC5 as a target of METTL3-mediated m6A modification through MeRIP-seq, and revealed that METTL3-mediated TXNDC5 expression relied on the m6A reader-dependent manner. METIL3 is believed to enhance the expression of Long intergenic non-protein coding RNA 426 (LINC00426) through m6A methylation modification.The LINC00426/miR-200a-3p/ZEB1 axis plays a crucial role in regulating E-cadherin, N-cadherin and vimentin during EMT in CC.Overexpression of LINC00426 in CC cells caused resistance to Cisplatin and Bleomycin, but sensitivity to imatinib." M6ADIS0008 35987795; 37392859 M6ADRUG0180 M6ACROT03515 REG00007 M6ATAR00980 Histone modification / Acetylation EPIREG00035 EPITAR00203 EPITAR00027 Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "The transcription factor ETS1 recruited p300 and WDR5 which separately mediated Histone H3 lysine 27 acetylation (H3K27ac) and H3K4me3 histone modification in the promoter of METTL3 and induced METTL3 transcription activation. Furthermore, we identified TXNDC5 as a target of METTL3-mediated m6A modification through MeRIP-seq, and revealed that METTL3-mediated TXNDC5 expression relied on the m6A reader-dependent manner. METIL3 is believed to enhance the expression of Long intergenic non-protein coding RNA 426 (LINC00426) through m6A methylation modification.The LINC00426/miR-200a-3p/ZEB1 axis plays a crucial role in regulating E-cadherin, N-cadherin and vimentin during EMT in CC.Overexpression of LINC00426 in CC cells caused resistance to Cisplatin and Bleomycin, but sensitivity to imatinib." M6ADIS0008 35987795; 37392859 M6ADRUG0107 M6ACROT03516 REG00007 M6ATAR01200 Histone modification / Acetylation EPIREG00035 EPITAR00203 EPITAR00027 . Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "The transcription factor ETS1 recruited p300 and WDR5 which separately mediated Histone H3 lysine 27 acetylation (H3K27ac) and H3K4me3 histone modification in the promoter of METTL3 and induced METTL3 transcription activation. Furthermore, we identified TXNDC5 as a target of METTL3-mediated m6A modification through MeRIP-seq, and revealed that METTL3-mediated TXNDC5 expression relied on the m6A reader-dependent manner. The METTL3-Serine/threonine-protein kinase Nek2 (NEK2) axis promoted CC progression by activating the Wnt/beta-catenin pathway and inhibiting the apoptosis pathway. In conclusion, METTL3 facilitated the malignant progression of CC and contributed to the formation of the METTL3-NEK2 regulatory axis in an m6A-dependent manner, which represented a potential target for CC therapy." M6ADIS0008 35987795; 39424828 . M6ACROT03517 REG00007 M6ATAR00112 Histone modification / Methylation EPIREG00066 EPITAR00204 EPITAR00027 . Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "The transcription factor ETS1 recruited P300 and WDR5 which separately mediated H3K27ac and Histone H3 lysine 4 trimethylation (H3K4me3) histone modification in the promoter of METTL3 and induced METTL3 transcription activation. Furthermore, we identified TXNDC5 as a target of METTL3-mediated m6A modification through MeRIP-seq, and revealed that METTL3-mediated TXNDC5 expression relied on the m6A reader-dependent manner. ZNFX1 antisense RNA 1 (ZFAS1) sequestered miR-647, and this RNA-RNA interaction is regulated by METLL3-mediated m6A modification in cervical cancer." M6ADIS0008 35987795; 33235466 . M6ACROT03518 REG00007 M6ATAR00094 Histone modification / Methylation EPIREG00066 EPITAR00204 EPITAR00027 Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "The transcription factor ETS1 recruited P300 and WDR5 which separately mediated H3K27ac and Histone H3 lysine 4 trimethylation (H3K4me3) histone modification in the promoter of METTL3 and induced METTL3 transcription activation. Furthermore, we identified TXNDC5 as a target of METTL3-mediated m6A modification through MeRIP-seq, and revealed that METTL3-mediated TXNDC5 expression relied on the m6A reader-dependent manner. METTL3/FOXD2 adjacent opposite strand RNA 1 (FOXD2-AS1) accelerates cervical cancer progression via a m6A-dependent modality, which serves as a potential therapeutic target for cervical cancer." M6ADIS0008 35987795; 34589576 . M6ACROT03519 REG00007 M6ATAR00533 Histone modification / Methylation EPIREG00066 EPITAR00204 EPITAR00027 Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "The transcription factor ETS1 recruited P300 and WDR5 which separately mediated H3K27ac and Histone H3 lysine 4 trimethylation (H3K4me3) histone modification in the promoter of METTL3 and induced METTL3 transcription activation. Furthermore, we identified TXNDC5 as a target of METTL3-mediated m6A modification through MeRIP-seq, and revealed that METTL3-mediated TXNDC5 expression relied on the m6A reader-dependent manner. METTL3 interacts with IGF2BP3 to promote the mRNA stability of Apoptotic chromatin condensation inducer in the nucleus (ACIN1), the overexpression of which induces the aggressiveness of CC cells." M6ADIS0008 35987795; 35255776 . M6ACROT03520 REG00007 M6ATAR00283 Histone modification / Methylation EPIREG00066 EPITAR00204 EPITAR00027 Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "The transcription factor ETS1 recruited P300 and WDR5 which separately mediated H3K27ac and Histone H3 lysine 4 trimethylation (H3K4me3) histone modification in the promoter of METTL3 and induced METTL3 transcription activation. Furthermore, we identified TXNDC5 as a target of METTL3-mediated m6A modification through MeRIP-seq, and revealed that METTL3-mediated TXNDC5 expression relied on the m6A reader-dependent manner. METTL3 enhanced the Hexokinase-2 (HK2) stability through YTHDF1-mediated m6A modification, thereby promoting the Warburg effect of CC, which promotes a novel insight for the CC treatment." M6ADIS0008 35987795; 33099572 . M6ACROT03521 REG00007 M6ATAR00599 Histone modification / Methylation EPIREG00066 EPITAR00204 EPITAR00027 Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "The transcription factor ETS1 recruited P300 and WDR5 which separately mediated H3K27ac and Histone H3 lysine 4 trimethylation (H3K4me3) histone modification in the promoter of METTL3 and induced METTL3 transcription activation. Furthermore, we identified TXNDC5 as a target of METTL3-mediated m6A modification through MeRIP-seq, and revealed that METTL3-mediated TXNDC5 expression relied on the m6A reader-dependent manner. METTL3 modulates miR-193b mature process in an m6A-dependent manner. Reintroduction of hsa-miR-193b profoundly inhibits tumorigenesis of cervical cancer cells both in vivo and in vitro through CCND1 targeting." M6ADIS0008 35987795; 34178650 . M6ACROT03522 REG00007 M6ATAR00206 Histone modification / Methylation EPIREG00066 EPITAR00204 EPITAR00027 Down regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "The transcription factor ETS1 recruited P300 and WDR5 which separately mediated H3K27ac and Histone H3 lysine 4 trimethylation (H3K4me3) histone modification in the promoter of METTL3 and induced METTL3 transcription activation. Furthermore, we identified TXNDC5 as a target of METTL3-mediated m6A modification through MeRIP-seq, and revealed that METTL3-mediated TXNDC5 expression relied on the m6A reader-dependent manner. METTL3 modulates miR-193b mature process in an m6A-dependent manner. Reintroduction of miR-193b profoundly inhibits tumorigenesis of cervical cancer cells both in vivo and in vitro through G1/S-specific cyclin-D1 (CCND1) targeting." M6ADIS0008 35987795; 34178650 . M6ACROT03523 REG00007 M6ATAR00729 Histone modification / Methylation EPIREG00066 EPITAR00204 EPITAR00027 . Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "The transcription factor ETS1 recruited P300 and WDR5 which separately mediated H3K27ac and Histone H3 lysine 4 trimethylation (H3K4me3) histone modification in the promoter of METTL3 and induced METTL3 transcription activation. Furthermore, we identified TXNDC5 as a target of METTL3-mediated m6A modification through MeRIP-seq, and revealed that METTL3-mediated TXNDC5 expression relied on the m6A reader-dependent manner. DARS-AS1 was validated to facilitate DARS translation via recruiting METTL3 and METTL14, which bound with DARS mRNA Aspartate--tRNA ligase, cytoplasmic (DARS) mRNA 5' untranslated region (5'UTR) and promoting its translation. The present study demonstrated that the 'HIF1-Alpha/DARS-AS1/DARS/ATG5/ATG3' pathway regulated the hypoxia-induced cytoprotective autophagy of cervical cancer(CC) and is a promising target of therapeutic strategies for patients afflicted with CC." M6ADIS0008 35987795; 35638109 . M6ACROT03524 REG00007 M6ATAR01450 Histone modification / Methylation EPIREG00066 EPITAR00204 EPITAR00027 Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "The transcription factor ETS1 recruited P300 and WDR5 which separately mediated H3K27ac and Histone H3 lysine 4 trimethylation (H3K4me3) histone modification in the promoter of METTL3 and induced METTL3 transcription activation. Furthermore, we identified TXNDC5 as a target of METTL3-mediated m6A modification through MeRIP-seq, and revealed that METTL3-mediated TXNDC5 expression relied on the m6A reader-dependent manner. METTL3 mediated the m6A modification of cathepsin L (Procathepsin L (CTSL)) mRNA at the 5'-UTR, and the m6A reader protein insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) bound to the m6A sites and enhanced CTSL mRNA stability. Our results indicated that METTL3 enhanced CTSL mRNA stability through an m6A-IGF2BP2-dependent mechanism, thereby promoting cervical cancer cell metastasis." M6ADIS0008 35987795; 36382580 . M6ACROT03525 REG00007 M6ATAR00966 Histone modification / Methylation EPIREG00066 EPITAR00204 EPITAR00027 Down regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "The transcription factor ETS1 recruited P300 and WDR5 which separately mediated H3K27ac and Histone H3 lysine 4 trimethylation (H3K4me3) histone modification in the promoter of METTL3 and induced METTL3 transcription activation. Furthermore, we identified TXNDC5 as a target of METTL3-mediated m6A modification through MeRIP-seq, and revealed that METTL3-mediated TXNDC5 expression relied on the m6A reader-dependent manner. METTL3/YTHDF2 promoted the degradation of Circ_RNF13 and subsequently affected the stability of CXC motif chemokine ligand 1 (CXCL1), ultimately enhancing the radiosensitivity of CC cells." M6ADIS0008 35987795; 37468464 . M6ACROT03526 REG00007 M6ATAR00980 Histone modification / Methylation EPIREG00066 EPITAR00204 EPITAR00027 Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "The transcription factor ETS1 recruited P300 and WDR5 which separately mediated H3K27ac and Histone H3 lysine 4 trimethylation (H3K4me3) histone modification in the promoter of METTL3 and induced METTL3 transcription activation. Furthermore, we identified TXNDC5 as a target of METTL3-mediated m6A modification through MeRIP-seq, and revealed that METTL3-mediated TXNDC5 expression relied on the m6A reader-dependent manner. METIL3 is believed to enhance the expression of Long intergenic non-protein coding RNA 426 (LINC00426) through m6A methylation modification.The LINC00426/miR-200a-3p/ZEB1 axis plays a crucial role in regulating E-cadherin, N-cadherin and vimentin during EMT in CC.Overexpression of LINC00426 in CC cells caused resistance to Cisplatin and Bleomycin, but sensitivity to imatinib." M6ADIS0008 35987795; 37392859 M6ADRUG0047 M6ACROT03527 REG00007 M6ATAR00980 Histone modification / Methylation EPIREG00066 EPITAR00204 EPITAR00027 Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "The transcription factor ETS1 recruited P300 and WDR5 which separately mediated H3K27ac and Histone H3 lysine 4 trimethylation (H3K4me3) histone modification in the promoter of METTL3 and induced METTL3 transcription activation. Furthermore, we identified TXNDC5 as a target of METTL3-mediated m6A modification through MeRIP-seq, and revealed that METTL3-mediated TXNDC5 expression relied on the m6A reader-dependent manner. METIL3 is believed to enhance the expression of Long intergenic non-protein coding RNA 426 (LINC00426) through m6A methylation modification.The LINC00426/miR-200a-3p/ZEB1 axis plays a crucial role in regulating E-cadherin, N-cadherin and vimentin during EMT in CC.Overexpression of LINC00426 in CC cells caused resistance to Cisplatin and Bleomycin, but sensitivity to imatinib." M6ADIS0008 35987795; 37392859 M6ADRUG0180 M6ACROT03528 REG00007 M6ATAR00980 Histone modification / Methylation EPIREG00066 EPITAR00204 EPITAR00027 Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "The transcription factor ETS1 recruited P300 and WDR5 which separately mediated H3K27ac and Histone H3 lysine 4 trimethylation (H3K4me3) histone modification in the promoter of METTL3 and induced METTL3 transcription activation. Furthermore, we identified TXNDC5 as a target of METTL3-mediated m6A modification through MeRIP-seq, and revealed that METTL3-mediated TXNDC5 expression relied on the m6A reader-dependent manner. METIL3 is believed to enhance the expression of Long intergenic non-protein coding RNA 426 (LINC00426) through m6A methylation modification.The LINC00426/miR-200a-3p/ZEB1 axis plays a crucial role in regulating E-cadherin, N-cadherin and vimentin during EMT in CC.Overexpression of LINC00426 in CC cells caused resistance to Cisplatin and Bleomycin, but sensitivity to imatinib." M6ADIS0008 35987795; 37392859 M6ADRUG0107 M6ACROT03529 REG00007 M6ATAR01200 Histone modification / Methylation EPIREG00066 EPITAR00204 EPITAR00027 . Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "The transcription factor ETS1 recruited P300 and WDR5 which separately mediated H3K27ac and Histone H3 lysine 4 trimethylation (H3K4me3) histone modification in the promoter of METTL3 and induced METTL3 transcription activation. Furthermore, we identified TXNDC5 as a target of METTL3-mediated m6A modification through MeRIP-seq, and revealed that METTL3-mediated TXNDC5 expression relied on the m6A reader-dependent manner. The METTL3-Serine/threonine-protein kinase Nek2 (NEK2) axis promoted CC progression by activating the Wnt/beta-catenin pathway and inhibiting the apoptosis pathway. In conclusion, METTL3 facilitated the malignant progression of CC and contributed to the formation of the METTL3-NEK2 regulatory axis in an m6A-dependent manner, which represented a potential target for CC therapy." M6ADIS0008 35987795; 39424828 . M6ACROT03530 REG00007 M6ATAR00606 Histone modification / Methylation EPIREG00054 EPITAR00201 EPITAR00027 Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "KDM1A-mediated upregulation of METTL3, which is caused by the abundant Histone H3 lysine 9 trimethylation (H3K9me3), ameliorates Alzheimer's disease via enhancing autophagic clearance of p-Tau through m6A-dependent regulation of STUB1. METTL3 rescues the A-Bete-induced reduction of Nucleolar protein 3 (ARC) expression via YTHDF1-Dependent m6A modification, which suggests an important mechanism of epigenetic alteration in AD." M6ADIS0089 36587923; 35547627 . M6ACROT03531 REG00007 M6ATAR01491 Histone modification / Methylation EPIREG00054 EPITAR00201 EPITAR00027 Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "KDM1A-mediated upregulation of METTL3, which is caused by the abundant Histone H3 lysine 9 trimethylation (H3K9me3), ameliorates Alzheimer's disease via enhancing autophagic clearance of p-Tau through m6A-dependent regulation of STUB1. METTL3 ablation attenuated the m6A modification in DNA methyltransferase 3A (Cysteine methyltransferase DNMT3A (DNMT3A)) mRNAs and consequently impaired YTH N6-methyladenosine RNA binding protein 1 (YTHDF1)-mediated translation of DNMT3A." M6ADIS0089 36587923; 36881554 . M6ACROT03532 REG00005 M6ATAR00787 Histone modification / Methylation EPIREG00066 EPITAR00204 EPITAR00183 . Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "Mechanically, the highly expressed ALKBH5 is induced by HBx-mediated Histone H3 lysine 4 trimethylation (H3K4me3) modification of ALKBH5 gene promoter in a WDR5-dependent manner after HBV infection. The increased ALKBH5 protein catalyzes the m6A demethylation of HBx mRNA, thus stabilizing and favoring a higher HBx expression level. circCPSF6 was dominated by ALKBH5-mediated demethylation, followed by the recognization and destabilization by YTHDF2. Meanwhile, circCPSF6 was upregulated in HCC specimens, and elevated hsa_circ_0000417 (circCPSF6) expression served as an independent prognostic factor for worse survival of patients with HCC." M6ADIS0006 34112124; 34916222 . M6ACROT03533 REG00005 M6ATAR00356 Histone modification / Methylation EPIREG00066 EPITAR00204 EPITAR00183 . Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "Mechanically, the highly expressed ALKBH5 is induced by HBx-mediated Histone H3 lysine 4 trimethylation (H3K4me3) modification of ALKBH5 gene promoter in a WDR5-dependent manner after HBV infection. The increased ALKBH5 protein catalyzes the m6A demethylation of HBx mRNA, thus stabilizing and favoring a higher HBx expression level. Deletion of METTL16 or ALKBH5 predicted poor OS and DFS of hepatocellular carcinoma (HCC) patients. And this study found significant associations between the genetic alterations and clinicopathological features as well as Cellular tumor antigen p53 (TP53/p53) alteration. " M6ADIS0006 34112124; 33133142 . M6ACROT03534 REG00005 M6ATAR00678 Histone modification / Methylation EPIREG00066 EPITAR00204 EPITAR00183 Down regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "Mechanically, the highly expressed ALKBH5 is induced by HBx-mediated Histone H3 lysine 4 trimethylation (H3K4me3) modification of ALKBH5 gene promoter in a WDR5-dependent manner after HBV infection. The increased ALKBH5 protein catalyzes the m6A demethylation of HBx mRNA, thus stabilizing and favoring a higher HBx expression level. ALKBH5 suppressed the proliferation and invasion capabilities of HCC cells in vitro and in vivo. Mechanistically, ALKBH5-mediated m6A demethylation led to a post-transcriptional inhibition of Ly6/PLAUR domain-containing protein 1 (LYPD1)." M6ADIS0006 34112124; 32772918 . M6ACROT03535 REG00005 M6ATAR00140 Histone modification / Methylation EPIREG00066 EPITAR00204 EPITAR00183 Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "Mechanically, the highly expressed ALKBH5 is induced by HBx-mediated Histone H3 lysine 4 trimethylation (H3K4me3) modification of ALKBH5 gene promoter in a WDR5-dependent manner after HBV infection. The increased ALKBH5 protein catalyzes the m6A demethylation of HBx mRNA, thus stabilizing and favoring a higher HBx expression level. ALKBH5 could up-regulate Nuclear paraspeckle assembly transcript 1 (NEAT1) expression by inhibiting m6A enrichment. ALKBH5-induced NEAT1 promoted cell proliferation and migration of HCC by sponging miR-214 in vitro, which provided a potential therapeutic target for HCC." M6ADIS0006 34112124; 35357550 . M6ACROT03536 REG00005 M6ATAR00895 Histone modification / Methylation EPIREG00066 EPITAR00204 EPITAR00183 Down regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "Mechanically, the highly expressed ALKBH5 is induced by HBx-mediated Histone H3 lysine 4 trimethylation (H3K4me3) modification of ALKBH5 gene promoter in a WDR5-dependent manner after HBV infection. The increased ALKBH5 protein catalyzes the m6A demethylation of HBx mRNA, thus stabilizing and favoring a higher HBx expression level. ALKBH5 decreases Progestin and adipoQ receptor family member 4 (PAQR4) mRNA and protein expression in an N6-methyladenosine (m6A)-dependent manner. The study also showed that ALKBH5 changes PAQR4 expression via the m6A reader IGF2BP1." M6ADIS0006 34112124; 36609413 . M6ACROT03537 REG00025 M6ATAR00453 Histone modification / Methylation EPIREG00053 EPITAR00204 EPITAR00487 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "KDM5B demethylated Histone H3 lysine 4 trimethylation (H3K4me3) on the MIR448 promoter and thereby inhibited the expression of miR-448, which in turn targeted YTHDF3 and integrin subunit alpha 6 (ITGA6) to promote the malignant phenotype of HCC. Moreover, KDM5B accelerated HCC progression in nude mice via the miR-448/YTHDF3/ITGA6 axis. circ_KIAA1429 could accelerate HCC advancement, maintained the expression of Zeb1 through the mechanism of m6A-YTHDF3-Zinc finger E-box-binding homeobox 1 (ZEB1) in hepatocellular carcinoma. " M6ADIS0006 33829656; 32653519 . M6ACROT03538 REG00025 M6ATAR00237 Histone modification / Methylation EPIREG00053 EPITAR00204 EPITAR00487 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "KDM5B demethylated Histone H3 lysine 4 trimethylation (H3K4me3) on the MIR448 promoter and thereby inhibited the expression of miR-448, which in turn targeted YTHDF3 and integrin subunit alpha 6 (ITGA6) to promote the malignant phenotype of HCC. Moreover, KDM5B accelerated HCC progression in nude mice via the miR-448/YTHDF3/ITGA6 axis. m6A reader YTHDF3 triggers the progression of hepatocellular carcinoma through the YTHDF3/m6A-Epidermal growth factor receptor (EGFR)/STAT3 axis and EMT" M6ADIS0006 33829656; 32653519 . M6ACROT03539 REG00008 M6ATAR00341 Histone modification / Methylation EPIREG00036 EPITAR00205 EPITAR00488 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways Histone methyltransferase EZH2 inhibited hsa-miR-454-3p through Histone H3 lysine 27 trimethylation (H3K27me3) and promoted m6A modification of PTEN/Myc proto-oncogene protein (MYC)/UBXN1/NF-Kappa-B to induce glioma M2 macrophage polarization. miR-454-3p promoted PTEN expression by inhibiting m6A modification through binding to the enzyme YTHDF2 M6ADIS0001 33363140 . M6ACROT03540 REG00008 M6ATAR00731 Histone modification / Methylation EPIREG00036 EPITAR00205 EPITAR00488 Down regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways Histone methyltransferase EZH2 inhibited hsa-miR-454-3p through Histone H3 lysine 27 trimethylation (H3K27me3) and promoted m6A modification of PTEN/MYC/UBX domain-containing protein 1 (UBXN1)/NF-Kappa-B to induce glioma M2 macrophage polarization. miR-454-3p promoted PTEN expression by inhibiting m6A modification through binding to the enzyme YTHDF2 M6ADIS0001 33363140 . M6ACROT03541 REG00008 M6ATAR00054 Histone modification / Methylation EPIREG00036 EPITAR00205 EPITAR00488 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways Histone methyltransferase EZH2 inhibited hsa-miR-454-3p through Histone H3 lysine 27 trimethylation (H3K27me3) and promoted m6A modification of PTEN/MYC/UBXN1/Nuclear factor NF-kappa-B p105 subunit (NF-Kappa-B/NFKB1) to induce glioma M2 macrophage polarization. miR-454-3p promoted PTEN expression by inhibiting m6A modification through binding to the enzyme YTHDF2 M6ADIS0001 33363140 . M6ACROT03542 REG00007 M6ATAR00404 Histone modification / Acetylation EPIREG00035 EPITAR00203 EPITAR00489 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "LINC01605 was regulated by SMYD2-p300-mediated modifications of histone H3K4me3 as well as Histone H3 lysine 27 acetylation (H3K27ac). LINC01605 was found to bind to METTL3 and promote the m6A modification of SPTBN2 mRNA, thereby facilitating the translation of SPTBN2. METTL3, acting as an oncogene, maintained Transcription factor SOX-2 (SOX2) expression through an m6A-IGF2BP2-dependent mechanism in CRC cells, and indicated a potential biomarker panel for prognostic prediction in Colorectal carcinoma." M6ADIS0059 34544413; 31230592 . M6ACROT03543 REG00007 M6ATAR00330 Histone modification / Acetylation EPIREG00035 EPITAR00203 EPITAR00489 Down regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "LINC01605 was regulated by SMYD2-p300-mediated modifications of histone H3K4me3 as well as Histone H3 lysine 27 acetylation (H3K27ac). LINC01605 was found to bind to METTL3 and promote the m6A modification of SPTBN2 mRNA, thereby facilitating the translation of SPTBN2. METTL3 played a tumor-suppressive role in Colorectal cancer cell proliferation, migration and invasion through Mitogen-activated protein kinase 14 (p38/MAPK14)/ERK pathways, which indicated that METTL3 was a novel marker for CRC carcinogenesis, progression and survival." M6ADIS0059 34544413; 31239708 . M6ACROT03544 REG00007 M6ATAR00244 Histone modification / Acetylation EPIREG00035 EPITAR00203 EPITAR00489 Down regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "LINC01605 was regulated by SMYD2-p300-mediated modifications of histone H3K4me3 as well as Histone H3 lysine 27 acetylation (H3K27ac). LINC01605 was found to bind to METTL3 and promote the m6A modification of SPTBN2 mRNA, thereby facilitating the translation of SPTBN2. METTL3 played a tumor-suppressive role in Colorectal cancer cell proliferation, migration and invasion through p38/Ephrin type-B receptor 2 (ERK/EPHB2) pathways, which indicated that METTL3 was a novel marker for CRC carcinogenesis, progression and survival." M6ADIS0059 34544413; 31239708 . M6ACROT03545 REG00007 M6ATAR00464 Histone modification / Acetylation EPIREG00035 EPITAR00203 EPITAR00489 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "LINC01605 was regulated by SMYD2-p300-mediated modifications of histone H3K4me3 as well as Histone H3 lysine 27 acetylation (H3K27ac). LINC01605 was found to bind to METTL3 and promote the m6A modification of SPTBN2 mRNA, thereby facilitating the translation of SPTBN2. METTL3/miR-1246/Sprouty-related, EVH1 domain-containing protein 2 (SPRED2) axis plays an important role in tumor metastasis and provides a new m6A modification pattern in Colorectal cancer development." M6ADIS0059 34544413; 31492150 . M6ACROT03546 REG00007 M6ATAR00109 Histone modification / Acetylation EPIREG00035 EPITAR00203 EPITAR00489 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "LINC01605 was regulated by SMYD2-p300-mediated modifications of histone H3K4me3 as well as Histone H3 lysine 27 acetylation (H3K27ac). LINC01605 was found to bind to METTL3 and promote the m6A modification of SPTBN2 mRNA, thereby facilitating the translation of SPTBN2. METTL3/microRNA 1246 (MIR1246)/SPRED2 axis plays an important role in tumor metastasis and provides a new m6A modification pattern in Colorectal cancer development." M6ADIS0059 34544413; 31492150 . M6ACROT03547 REG00007 M6ATAR00208 Histone modification / Acetylation EPIREG00035 EPITAR00203 EPITAR00489 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "LINC01605 was regulated by SMYD2-p300-mediated modifications of histone H3K4me3 as well as Histone H3 lysine 27 acetylation (H3K27ac). LINC01605 was found to bind to METTL3 and promote the m6A modification of SPTBN2 mRNA, thereby facilitating the translation of SPTBN2. METTL3 promotes colorectal cancer proliferation by stabilizing G1/S-specific cyclin-E1 (CCNE1) mRNA in an m6A-dependent manner, representing a promising therapeutic strategy for the treatment of CRC." M6ADIS0059 34544413; 32039568 . M6ACROT03548 REG00007 M6ATAR00283 Histone modification / Acetylation EPIREG00035 EPITAR00203 EPITAR00489 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "LINC01605 was regulated by SMYD2-p300-mediated modifications of histone H3K4me3 as well as Histone H3 lysine 27 acetylation (H3K27ac). LINC01605 was found to bind to METTL3 and promote the m6A modification of SPTBN2 mRNA, thereby facilitating the translation of SPTBN2. METTL3 stabilizes Hexokinase-2 (HK2) and SLC2A1 (GLUT1) expression in colorectal cancer through an m6A-IGF2BP2/3- dependent mechanism." M6ADIS0059 34544413; 32245489 . M6ACROT03549 REG00007 M6ATAR00269 Histone modification / Acetylation EPIREG00035 EPITAR00203 EPITAR00489 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "LINC01605 was regulated by SMYD2-p300-mediated modifications of histone H3K4me3 as well as Histone H3 lysine 27 acetylation (H3K27ac). LINC01605 was found to bind to METTL3 and promote the m6A modification of SPTBN2 mRNA, thereby facilitating the translation of SPTBN2. METTL3 stabilizes HK2 and Glucose transporter type 1 (SLC2A1) (GLUT1) expression in colorectal cancer through an m6A-IGF2BP2/3- dependent mechanism." M6ADIS0059 34544413; 32245489 . M6ACROT03550 REG00007 M6ATAR00341 Histone modification / Acetylation EPIREG00035 EPITAR00203 EPITAR00489 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "LINC01605 was regulated by SMYD2-p300-mediated modifications of histone H3K4me3 as well as Histone H3 lysine 27 acetylation (H3K27ac). LINC01605 was found to bind to METTL3 and promote the m6A modification of SPTBN2 mRNA, thereby facilitating the translation of SPTBN2. METTL3 exerted its function through enhancing Myc proto-oncogene protein (MYC) expression, at least partially in an m6A-IGF2BP1-dependent manner. Knockdown of METTL3 suppressed colorectal cancer cell proliferation in vitro and in vivo." M6ADIS0059 34544413; 32509177 . M6ACROT03551 REG00007 M6ATAR00149 Histone modification / Acetylation EPIREG00035 EPITAR00203 EPITAR00489 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "LINC01605 was regulated by SMYD2-p300-mediated modifications of histone H3K4me3 as well as Histone H3 lysine 27 acetylation (H3K27ac). LINC01605 was found to bind to METTL3 and promote the m6A modification of SPTBN2 mRNA, thereby facilitating the translation of SPTBN2. Overexpression of METTL3 upregulates Long intergenic non-protein coding RNA 2598 (LINC02598/RP11) expression in colorectal cancer cells. Overexpression of ALKBH5 downregulates RP11 expression." M6ADIS0059 34544413; 33335959 . M6ACROT03552 REG00007 M6ATAR00476 Histone modification / Acetylation EPIREG00035 EPITAR00203 EPITAR00489 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "LINC01605 was regulated by SMYD2-p300-mediated modifications of histone H3K4me3 as well as Histone H3 lysine 27 acetylation (H3K27ac). LINC01605 was found to bind to METTL3 and promote the m6A modification of SPTBN2 mRNA, thereby facilitating the translation of SPTBN2. LINC00460 is a novel oncogene of colorectal cancer through interacting with IGF2BP2 and DHX9 and bind to the m6A modified High mobility group protein HMG-I/HMG-Y (HMGA1) mRNA to enhance the HMGA1 mRNA stability. The N6-methyladenosine (m6A) modification of HMGA1 mRNA by METTL3 enhanced HMGA1 expression in CRC." M6ADIS0059 34544413; 33526059 . M6ACROT03553 REG00007 M6ATAR00100 Histone modification / Acetylation EPIREG00035 EPITAR00203 EPITAR00489 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "LINC01605 was regulated by SMYD2-p300-mediated modifications of histone H3K4me3 as well as Histone H3 lysine 27 acetylation (H3K27ac). LINC01605 was found to bind to METTL3 and promote the m6A modification of SPTBN2 mRNA, thereby facilitating the translation of SPTBN2. Long intergenic non-protein coding RNA 460 (LINC00460) is a novel oncogene of colorectal cancer through interacting with IGF2BP2 and DHX9 and bind to the m6A modified HMGA1 mRNA to enhance the HMGA1 mRNA stability. The N6-methyladenosine (m6A) modification of HMGA1 mRNA by METTL3 enhanced HMGA1 expression in CRC." M6ADIS0059 34544413; 33526059 . M6ACROT03554 REG00007 M6ATAR00036 Histone modification / Acetylation EPIREG00035 EPITAR00203 EPITAR00489 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "LINC01605 was regulated by SMYD2-p300-mediated modifications of histone H3K4me3 as well as Histone H3 lysine 27 acetylation (H3K27ac). LINC01605 was found to bind to METTL3 and promote the m6A modification of SPTBN2 mRNA, thereby facilitating the translation of SPTBN2. METTL3-induced Circ_1662 promoted colorectal cancer cell invasion and migration by accelerating YAP1 nuclear transport. Circ1662 enhanced CRC invasion and migration depending on YAP1 and SMAD3. This result implies that circ1662 is a new prognostic and therapeutic marker for CRC metastasis." M6ADIS0059 34544413; 33754062 . M6ACROT03555 REG00007 M6ATAR00451 Histone modification / Acetylation EPIREG00035 EPITAR00203 EPITAR00489 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "LINC01605 was regulated by SMYD2-p300-mediated modifications of histone H3K4me3 as well as Histone H3 lysine 27 acetylation (H3K27ac). LINC01605 was found to bind to METTL3 and promote the m6A modification of SPTBN2 mRNA, thereby facilitating the translation of SPTBN2. METTL3-induced circ1662 promoted colorectal cancer cell invasion and migration by accelerating Transcriptional coactivator YAP1 (YAP1) nuclear transport. Circ1662 enhanced CRC invasion and migration depending on YAP1 and SMAD3. This result implies that circ1662 is a new prognostic and therapeutic marker for CRC metastasis." M6ADIS0059 34544413; 33754062 . M6ACROT03556 REG00007 M6ATAR00396 Histone modification / Acetylation EPIREG00035 EPITAR00203 EPITAR00489 Down regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "LINC01605 was regulated by SMYD2-p300-mediated modifications of histone H3K4me3 as well as Histone H3 lysine 27 acetylation (H3K27ac). LINC01605 was found to bind to METTL3 and promote the m6A modification of SPTBN2 mRNA, thereby facilitating the translation of SPTBN2. METTL3-induced circ1662 promoted colorectal cancer cell invasion and migration by accelerating YAP1 nuclear transport. Circ1662 enhanced CRC invasion and migration depending on YAP1 and Mothers against decapentaplegic homolog 3 (SMAD3). This result implies that circ1662 is a new prognostic and therapeutic marker for CRC metastasis." M6ADIS0059 34544413; 33754062 . M6ACROT03557 REG00007 M6ATAR00389 Histone modification / Acetylation EPIREG00035 EPITAR00203 EPITAR00489 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "LINC01605 was regulated by SMYD2-p300-mediated modifications of histone H3K4me3 as well as Histone H3 lysine 27 acetylation (H3K27ac). LINC01605 was found to bind to METTL3 and promote the m6A modification of SPTBN2 mRNA, thereby facilitating the translation of SPTBN2. Translocation protein SEC62 (SEC62) upregulated by the METTL3-mediated m6A modification promotes the stemness and chemoresistance of colorectal cancer by binding to beta-catenin and enhancing Wnt signalling. Depletion of Sec62 sensitized the CRC cells to 5-Fu or oxaliplatin treatment." M6ADIS0059 34544413; 33858476 M6ADRUG0048 M6ACROT03558 REG00007 M6ATAR00389 Histone modification / Acetylation EPIREG00035 EPITAR00203 EPITAR00489 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "LINC01605 was regulated by SMYD2-p300-mediated modifications of histone H3K4me3 as well as Histone H3 lysine 27 acetylation (H3K27ac). LINC01605 was found to bind to METTL3 and promote the m6A modification of SPTBN2 mRNA, thereby facilitating the translation of SPTBN2. Translocation protein SEC62 (SEC62) upregulated by the METTL3-mediated m6A modification promotes the stemness and chemoresistance of colorectal cancer by binding to beta-catenin and enhancing Wnt signalling. Depletion of Sec62 sensitized the CRC cells to 5-Fu or oxaliplatin treatment." M6ADIS0059 34544413; 33858476 M6ADRUG0005 M6ACROT03559 REG00007 M6ATAR00146 Histone modification / Acetylation EPIREG00035 EPITAR00203 EPITAR00489 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "LINC01605 was regulated by SMYD2-p300-mediated modifications of histone H3K4me3 as well as Histone H3 lysine 27 acetylation (H3K27ac). LINC01605 was found to bind to METTL3 and promote the m6A modification of SPTBN2 mRNA, thereby facilitating the translation of SPTBN2. The increased LBX2 antisense RNA 1 (LBX2-AS1) in CRC was mediated by METTL3-dependent m6A methylation. LBX2-AS1 serves as a therapeutic target and predictor of 5-FU benefit in colorectal cancer patients." M6ADIS0059 34544413; 34535128 M6ADRUG0005 M6ACROT03560 REG00007 M6ATAR00377 Histone modification / Acetylation EPIREG00035 EPITAR00203 EPITAR00489 Down regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "LINC01605 was regulated by SMYD2-p300-mediated modifications of histone H3K4me3 as well as Histone H3 lysine 27 acetylation (H3K27ac). LINC01605 was found to bind to METTL3 and promote the m6A modification of SPTBN2 mRNA, thereby facilitating the translation of SPTBN2. In colorectal cancer, n6-methyladenosine (m6A) subunit METTL3 increased PTTG3P expression by influencing its stability, while insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) could identify Putative pituitary tumor-transforming gene 3 protein (PTTG3P) m6A methylation status and bind to it." M6ADIS0059 34544413; 34660259 . M6ACROT03561 REG00007 M6ATAR00757 Histone modification / Acetylation EPIREG00035 EPITAR00203 EPITAR00489 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "LINC01605 was regulated by SMYD2-p300-mediated modifications of histone H3K4me3 as well as Histone H3 lysine 27 acetylation (H3K27ac). LINC01605 was found to bind to METTL3 and promote the m6A modification of SPTBN2 mRNA, thereby facilitating the translation of SPTBN2. METTL3 promoted Class E basic helix-loop-helix protein 41 (BHLHE41) expression in m6A-dependent manner, which subsequently induced CXCL1 transcription to enhance MDSC migration in vitro. METTL3 as a potential therapeutic target for CRC immunotherapy whose inhibition reverses immune suppression through m6A-BHLHE41-CXCL1 axis." M6ADIS0059 34544413; 35700773 . M6ACROT03562 REG00007 M6ATAR00762 Histone modification / Acetylation EPIREG00035 EPITAR00203 EPITAR00489 Down regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "LINC01605 was regulated by SMYD2-p300-mediated modifications of histone H3K4me3 as well as Histone H3 lysine 27 acetylation (H3K27ac). LINC01605 was found to bind to METTL3 and promote the m6A modification of SPTBN2 mRNA, thereby facilitating the translation of SPTBN2. m6A and METTL3 levels were substantially elevated in colorectal carcinoma(CRC) tissues, METTL3 knockdown substantially reduced the m6A level of Protein crumbs homolog 3 (CRB3), and inhibited the degradation of CRB3 mRNA to increase CRB3 expression. METTL3 regulated the progression of CRC by regulating the m6A-CRB3-Hippo pathway." M6ADIS0059 34544413; 35012593 . M6ACROT03563 REG00007 M6ATAR00771 Histone modification / Acetylation EPIREG00035 EPITAR00203 EPITAR00489 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "LINC01605 was regulated by SMYD2-p300-mediated modifications of histone H3K4me3 as well as Histone H3 lysine 27 acetylation (H3K27ac). LINC01605 was found to bind to METTL3 and promote the m6A modification of SPTBN2 mRNA, thereby facilitating the translation of SPTBN2. METTL3 enhances the expression of Lactate dehydrogenase A (LDHA), which catalyzes the conversion of pyruvate to lactate, to trigger glycolysis and 5-FU resistance. METTL3/LDHA axis-induced glucose metabolism is a potential therapy target to overcome 5-FU resistance in CRC cells." M6ADIS0059 34544413; 35832094 . M6ACROT03564 REG00007 M6ATAR00773 Histone modification / Acetylation EPIREG00035 EPITAR00203 EPITAR00489 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "LINC01605 was regulated by SMYD2-p300-mediated modifications of histone H3K4me3 as well as Histone H3 lysine 27 acetylation (H3K27ac). LINC01605 was found to bind to METTL3 and promote the m6A modification of SPTBN2 mRNA, thereby facilitating the translation of SPTBN2. METTL3 augmented 5 FU induced DNA damage and overcame 5 FU resistance in HCT 8R cells, which could be mimicked by inhibition of RAD51-associated protein 1 (RAD51AP1). The present study revealed that the METTL3/RAD51AP1 axis plays an important role in the acquisition of 5 FU resistance in CRC." M6ADIS0059 34544413; 35856434 M6ADRUG0005 M6ACROT03565 REG00007 M6ATAR01672 Histone modification / Acetylation EPIREG00035 EPITAR00203 EPITAR00489 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "LINC01605 was regulated by SMYD2-p300-mediated modifications of histone H3K4me3 as well as Histone H3 lysine 27 acetylation (H3K27ac). LINC01605 was found to bind to METTL3 and promote the m6A modification of SPTBN2 mRNA, thereby facilitating the translation of SPTBN2. hsa_circ_0000677 and its downstream target ABCC1 were upregulated in CRC cells, induced by the METTL3-mediated m6A modification of circ_0000677 and SUMO1-mediated SUMOylation of METTL3. This work provided a new strategy for the therapeutic treatment of CRC." M6ADIS0059 34544413; 35030640 . M6ACROT03566 REG00007 M6ATAR00521 Histone modification / Acetylation EPIREG00035 EPITAR00203 EPITAR00489 Down regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "LINC01605 was regulated by SMYD2-p300-mediated modifications of histone H3K4me3 as well as Histone H3 lysine 27 acetylation (H3K27ac). LINC01605 was found to bind to METTL3 and promote the m6A modification of SPTBN2 mRNA, thereby facilitating the translation of SPTBN2. In colorectal cancer, Mettl3- or Mettl14-deficient tumors increased cytotoxic tumor-infiltrating CD8+ T cells and elevated secretion of Interferon gamma (IFN-gamma), Cxcl9, and Cxcl10 in tumor microenvironment in vivo. Mechanistically, Mettl3 or Mettl14 loss promoted IFN-gamma-Stat1-Irf1 signaling through stabilizing the Stat1 and Irf1 mRNA via Ythdf2." M6ADIS0059 34544413; 32964498 . M6ACROT03567 REG00007 M6ATAR00522 Histone modification / Acetylation EPIREG00035 EPITAR00203 EPITAR00489 Down regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "LINC01605 was regulated by SMYD2-p300-mediated modifications of histone H3K4me3 as well as Histone H3 lysine 27 acetylation (H3K27ac). LINC01605 was found to bind to METTL3 and promote the m6A modification of SPTBN2 mRNA, thereby facilitating the translation of SPTBN2. In colorectal cancer, Mettl3- or Mettl14-deficient tumors increased cytotoxic tumor-infiltrating CD8+ T cells and elevated secretion of IFN-gamma, C-X-C motif chemokine 9 (Cxcl9), and Cxcl10 in tumor microenvironment in vivo. Mechanistically, Mettl3 or Mettl14 loss promoted IFN-gamma-Stat1-Irf1 signaling through stabilizing the Stat1 and Irf1 mRNA via Ythdf2." M6ADIS0059 34544413; 32964498 . M6ACROT03568 REG00007 M6ATAR00523 Histone modification / Acetylation EPIREG00035 EPITAR00203 EPITAR00489 Down regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "LINC01605 was regulated by SMYD2-p300-mediated modifications of histone H3K4me3 as well as Histone H3 lysine 27 acetylation (H3K27ac). LINC01605 was found to bind to METTL3 and promote the m6A modification of SPTBN2 mRNA, thereby facilitating the translation of SPTBN2. In colorectal cancer, Mettl3- or Mettl14-deficient tumors increased cytotoxic tumor-infiltrating CD8+ T cells and elevated secretion of IFN-gamma, Cxcl9, and C-X-C motif chemokine 10 (Cxcl10) in tumor microenvironment in vivo. Mechanistically, Mettl3 or Mettl14 loss promoted IFN-gamma-Stat1-Irf1 signaling through stabilizing the Stat1 and Irf1 mRNA via Ythdf2." M6ADIS0059 34544413; 32964498 . M6ACROT03569 REG00007 M6ATAR00524 Histone modification / Acetylation EPIREG00035 EPITAR00203 EPITAR00489 Down regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "LINC01605 was regulated by SMYD2-p300-mediated modifications of histone H3K4me3 as well as Histone H3 lysine 27 acetylation (H3K27ac). LINC01605 was found to bind to METTL3 and promote the m6A modification of SPTBN2 mRNA, thereby facilitating the translation of SPTBN2. In colorectal cancer, Mettl3- or Mettl14-deficient tumors increased cytotoxic tumor-infiltrating CD8+ T cells and elevated secretion of IFN-gamma, Cxcl9, and Cxcl10 in tumor microenvironment in vivo. Mechanistically, Mettl3 or Mettl14 loss promoted IFN-gamma-Stat1-Irf1 signaling through stabilizing the Transcription factor ISGF-3 components p91/p84 (Stat1) and Irf1 mRNA via Ythdf2." M6ADIS0059 34544413; 32964498 . M6ACROT03570 REG00007 M6ATAR00525 Histone modification / Acetylation EPIREG00035 EPITAR00203 EPITAR00489 Down regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "LINC01605 was regulated by SMYD2-p300-mediated modifications of histone H3K4me3 as well as Histone H3 lysine 27 acetylation (H3K27ac). LINC01605 was found to bind to METTL3 and promote the m6A modification of SPTBN2 mRNA, thereby facilitating the translation of SPTBN2. In colorectal cancer, Mettl3- or Mettl14-deficient tumors increased cytotoxic tumor-infiltrating CD8+ T cells and elevated secretion of IFN-gamma, Cxcl9, and Cxcl10 in tumor microenvironment in vivo. Mechanistically, Mettl3 or Mettl14 loss promoted IFN-gamma-Stat1-Irf1 signaling through stabilizing the Stat1 and Interferon regulatory factor 1 (Irf1) mRNA via Ythdf2." M6ADIS0059 34544413; 32964498 . M6ACROT03571 REG00007 M6ATAR00269 Histone modification / Acetylation EPIREG00035 EPITAR00203 EPITAR00489 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "LINC01605 was regulated by SMYD2-p300-mediated modifications of histone H3K4me3 as well as Histone H3 lysine 27 acetylation (H3K27ac). LINC01605 was found to bind to METTL3 and promote the m6A modification of SPTBN2 mRNA, thereby facilitating the translation of SPTBN2. METTL3 induced Glucose transporter type 1 (SLC2A1) translation in an m6A-dependent manner, which subsequently promoted glucose uptake and lactate production, leading to the activation of mTORC1 signaling and CRC development. " M6ADIS0059 34544413; 33217448 . M6ACROT03572 REG00007 M6ATAR00399 Histone modification / Acetylation EPIREG00035 EPITAR00203 EPITAR00489 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "LINC01605 was regulated by SMYD2-p300-mediated modifications of histone H3K4me3 as well as Histone H3 lysine 27 acetylation (H3K27ac). LINC01605 was found to bind to METTL3 and promote the m6A modification of SPTBN2 mRNA, thereby facilitating the translation of SPTBN2. METTL3 acts as a critical m6A methyltransferase capable of facilitating colorectal cancer(CRC) progression, and revealed a novel mechanism by which METTL3 promotes CRC cell proliferation and invasion via stabilizing Zinc finger protein SNAI1 (SNAI1) mRNA in an m6A-dependent manner. " M6ADIS0059 34544413; 34457066 . M6ACROT03573 REG00007 M6ATAR00663 Histone modification / Acetylation EPIREG00035 EPITAR00203 EPITAR00489 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "LINC01605 was regulated by SMYD2-p300-mediated modifications of histone H3K4me3 as well as Histone H3 lysine 27 acetylation (H3K27ac). LINC01605 was found to bind to METTL3 and promote the m6A modification of SPTBN2 mRNA, thereby facilitating the translation of SPTBN2. METTL3 upregulated Urokinase-type plasminogen activator (PLAU) mRNA in an m6A-dependent manner, and then participated in MAPK/ERK pathway to promote angiogenesis and metastasis in CRC." M6ADIS0059 34544413; 35567945 . M6ACROT03574 REG00007 M6ATAR00666 Histone modification / Acetylation EPIREG00035 EPITAR00203 EPITAR00489 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "LINC01605 was regulated by SMYD2-p300-mediated modifications of histone H3K4me3 as well as Histone H3 lysine 27 acetylation (H3K27ac). LINC01605 was found to bind to METTL3 and promote the m6A modification of SPTBN2 mRNA, thereby facilitating the translation of SPTBN2. METTL3 dependent m6A methylation was upregulated in CRC to promote the processing of miR 181d 5p by DGCR8. This led to increased hsa-miR-181d-5p expression, which inhibited the 5 FU sensitivity of CRC cells by targeting NCALD." M6ADIS0059 34544413; 35014676 M6ADRUG0005 M6ACROT03575 REG00007 M6ATAR00667 Histone modification / Acetylation EPIREG00035 EPITAR00203 EPITAR00489 Down regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "LINC01605 was regulated by SMYD2-p300-mediated modifications of histone H3K4me3 as well as Histone H3 lysine 27 acetylation (H3K27ac). LINC01605 was found to bind to METTL3 and promote the m6A modification of SPTBN2 mRNA, thereby facilitating the translation of SPTBN2. METTL3 dependent m6A methylation was upregulated in CRC to promote the processing of miR 181d 5p by DGCR8. This led to increased miR 181d 5p expression, which inhibited the 5 FU sensitivity of CRC cells by targeting Neurocalcin-delta (NCALD)." M6ADIS0059 34544413; 35014676 M6ADRUG0005 M6ACROT03576 REG00007 M6ATAR00671 Histone modification / Acetylation EPIREG00035 EPITAR00203 EPITAR00489 Down regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "LINC01605 was regulated by SMYD2-p300-mediated modifications of histone H3K4me3 as well as Histone H3 lysine 27 acetylation (H3K27ac). LINC01605 was found to bind to METTL3 and promote the m6A modification of SPTBN2 mRNA, thereby facilitating the translation of SPTBN2. 2-polarized tumor-associated macrophages enabled the oxaliplatin resistance via the elevation of METTL3-mediated m6A modification in Colorectal Cancer cells. Furthermore, they found that TNF receptor-associated factor 5 (TRAF5) contributes to the METTL3-triggered OX resistance in CRC cells." M6ADIS0059 34544413; 33555197 M6ADRUG0048 M6ACROT03577 REG00007 M6ATAR00680 Histone modification / Acetylation EPIREG00035 EPITAR00203 EPITAR00489 Down regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "LINC01605 was regulated by SMYD2-p300-mediated modifications of histone H3K4me3 as well as Histone H3 lysine 27 acetylation (H3K27ac). LINC01605 was found to bind to METTL3 and promote the m6A modification of SPTBN2 mRNA, thereby facilitating the translation of SPTBN2. METTL3-catalyzed m6A modification in CRC tumorigenesis, wherein it facilitates CRC tumor growth and metastasis through suppressing Protein yippee-like 5 (YPEL5) expression in an m6A-YTHDF2-dependent manner." M6ADIS0059 34544413; 33411363 . M6ACROT03578 REG00007 M6ATAR00716 Histone modification / Acetylation EPIREG00035 EPITAR00203 EPITAR00489 . Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "LINC01605 was regulated by SMYD2-p300-mediated modifications of histone H3K4me3 as well as Histone H3 lysine 27 acetylation (H3K27ac). LINC01605 was found to bind to METTL3 and promote the m6A modification of SPTBN2 mRNA, thereby facilitating the translation of SPTBN2. Ephrin type-A receptor 2 (EphA2) and VEGFA targeted by METTL3 via different IGF2BP-dependent mechanisms were found to promote vasculogenic mimicry (VM) formation via PI3K/AKT/mTOR and ERK1/2 signaling in CRC." M6ADIS0059 34544413; 35595748 . M6ACROT03579 REG00007 M6ATAR00446 Histone modification / Acetylation EPIREG00035 EPITAR00203 EPITAR00489 . Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "LINC01605 was regulated by SMYD2-p300-mediated modifications of histone H3K4me3 as well as Histone H3 lysine 27 acetylation (H3K27ac). LINC01605 was found to bind to METTL3 and promote the m6A modification of SPTBN2 mRNA, thereby facilitating the translation of SPTBN2. EphA2 and Vascular endothelial growth factor A (VEGFA) targeted by METTL3 via different IGF2BP-dependent mechanisms were found to promote vasculogenic mimicry (VM) formation via PI3K/AKT/mTOR and ERK1/2 signaling in CRC." M6ADIS0059 34544413; 35595748 . M6ACROT03580 REG00007 M6ATAR01425 Histone modification / Acetylation EPIREG00035 EPITAR00203 EPITAR00489 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "LINC01605 was regulated by SMYD2-p300-mediated modifications of histone H3K4me3 as well as Histone H3 lysine 27 acetylation (H3K27ac). LINC01605 was found to bind to METTL3 and promote the m6A modification of SPTBN2 mRNA, thereby facilitating the translation of SPTBN2. the malignant behaviors governed by Lithostathine-1-alpha (REG1A) could be effectively abolished by silencing of Wnt/beta-catenin/MYC axis or glycolysis process using specific inhibitors. Besides, REG1alpha expression was mediated by METTL3 in an m6A-dependent manner." M6ADIS0059 34544413; 37626036 . M6ACROT03581 REG00007 M6ATAR00836 Histone modification / Acetylation EPIREG00035 EPITAR00203 EPITAR00489 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "LINC01605 was regulated by SMYD2-p300-mediated modifications of histone H3K4me3 as well as Histone H3 lysine 27 acetylation (H3K27ac). LINC01605 was found to bind to METTL3 and promote the m6A modification of SPTBN2 mRNA, thereby facilitating the translation of SPTBN2. Tl increased the level of aberrant N6-methyladenosine (m6A) modification of Polyamine-transporting ATPase 13A3 (ATP13A3) via the METLL3/METTL14/ALKBH5-ATP13A3 axis to promote colorectal tumorigenesis." M6ADIS0059 34544413; 36745568 . M6ACROT03582 REG00007 M6ATAR00117 Histone modification / Acetylation EPIREG00035 EPITAR00203 EPITAR00489 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "LINC01605 was regulated by SMYD2-p300-mediated modifications of histone H3K4me3 as well as Histone H3 lysine 27 acetylation (H3K27ac). LINC01605 was found to bind to METTL3 and promote the m6A modification of SPTBN2 mRNA, thereby facilitating the translation of SPTBN2. METTL3 promotes proliferation and migration of colorectal cancer cells by increasing Small nucleolar RNA host gene 1 (SNHG1) stability" M6ADIS0059 34544413; 37772373 . M6ACROT03583 REG00007 M6ATAR00981 Histone modification / Acetylation EPIREG00035 EPITAR00203 EPITAR00489 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "LINC01605 was regulated by SMYD2-p300-mediated modifications of histone H3K4me3 as well as Histone H3 lysine 27 acetylation (H3K27ac). LINC01605 was found to bind to METTL3 and promote the m6A modification of SPTBN2 mRNA, thereby facilitating the translation of SPTBN2. METTL3-Modulated Circ_UHRF2 Promotes Colorectal Cancer Stemness and Metastasis through Increasing DDX27 mRNA Stability by Recruiting IGF2BP1" M6ADIS0059 34544413; 37370759 . M6ACROT03584 REG00007 M6ATAR00982 Histone modification / Acetylation EPIREG00035 EPITAR00203 EPITAR00489 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "LINC01605 was regulated by SMYD2-p300-mediated modifications of histone H3K4me3 as well as Histone H3 lysine 27 acetylation (H3K27ac). LINC01605 was found to bind to METTL3 and promote the m6A modification of SPTBN2 mRNA, thereby facilitating the translation of SPTBN2. The METTL3/IGF2BP2/Cohesin subunit SA-3 (STAG3) axis affects CRC progression in an m6A modification-dependent manner. This may guide targeted therapy in CRC patients." M6ADIS0059 34544413; 37828232 . M6ACROT03585 REG00007 M6ATAR01005 Histone modification / Acetylation EPIREG00035 EPITAR00203 EPITAR00489 . Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "LINC01605 was regulated by SMYD2-p300-mediated modifications of histone H3K4me3 as well as Histone H3 lysine 27 acetylation (H3K27ac). LINC01605 was found to bind to METTL3 and promote the m6A modification of SPTBN2 mRNA, thereby facilitating the translation of SPTBN2. METTL3 regulates miR-196b expression via an N6-methyladenosine (m6A)-pri-miR-196b-dependent mechanism and thereby promotes CRC metastasis." M6ADIS0059 34544413; 36348020 . M6ACROT03586 REG00007 M6ATAR01058 Histone modification / Acetylation EPIREG00035 EPITAR00203 EPITAR00489 Down regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "LINC01605 was regulated by SMYD2-p300-mediated modifications of histone H3K4me3 as well as Histone H3 lysine 27 acetylation (H3K27ac). LINC01605 was found to bind to METTL3 and promote the m6A modification of SPTBN2 mRNA, thereby facilitating the translation of SPTBN2. METTL3 mediated m6A methylation of hsa_circ_0124554.m6A-modified circ_0124554 promoted CRC progression and radioresistance by inducing LASP1 expression through interaction with miR-1184." M6ADIS0059 34544413; 38091882 . M6ACROT03587 REG00007 M6ATAR00404 Histone modification / Methylation EPIREG00071 EPITAR00204 EPITAR00489 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "LINC01605 was regulated by SMYD2-EP300-mediated modifications of histone Histone H3 lysine 4 trimethylation (H3K4me3) as well as H3K27ac. LINC01605 was found to bind to METTL3 and promote the m6A modification of SPTBN2 mRNA, thereby facilitating the translation of SPTBN2. METTL3, acting as an oncogene, maintained Transcription factor SOX-2 (SOX2) expression through an m6A-IGF2BP2-dependent mechanism in CRC cells, and indicated a potential biomarker panel for prognostic prediction in Colorectal carcinoma." M6ADIS0059 34544413; 31230592 . M6ACROT03588 REG00007 M6ATAR00330 Histone modification / Methylation EPIREG00071 EPITAR00204 EPITAR00489 Down regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "LINC01605 was regulated by SMYD2-EP300-mediated modifications of histone Histone H3 lysine 4 trimethylation (H3K4me3) as well as H3K27ac. LINC01605 was found to bind to METTL3 and promote the m6A modification of SPTBN2 mRNA, thereby facilitating the translation of SPTBN2. METTL3 played a tumor-suppressive role in Colorectal cancer cell proliferation, migration and invasion through Mitogen-activated protein kinase 14 (p38/MAPK14)/ERK pathways, which indicated that METTL3 was a novel marker for CRC carcinogenesis, progression and survival." M6ADIS0059 34544413; 31239708 . M6ACROT03589 REG00007 M6ATAR00244 Histone modification / Methylation EPIREG00071 EPITAR00204 EPITAR00489 Down regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "LINC01605 was regulated by SMYD2-EP300-mediated modifications of histone Histone H3 lysine 4 trimethylation (H3K4me3) as well as H3K27ac. LINC01605 was found to bind to METTL3 and promote the m6A modification of SPTBN2 mRNA, thereby facilitating the translation of SPTBN2. METTL3 played a tumor-suppressive role in Colorectal cancer cell proliferation, migration and invasion through p38/Ephrin type-B receptor 2 (ERK/EPHB2) pathways, which indicated that METTL3 was a novel marker for CRC carcinogenesis, progression and survival." M6ADIS0059 34544413; 31239708 . M6ACROT03590 REG00007 M6ATAR00464 Histone modification / Methylation EPIREG00071 EPITAR00204 EPITAR00489 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "LINC01605 was regulated by SMYD2-EP300-mediated modifications of histone Histone H3 lysine 4 trimethylation (H3K4me3) as well as H3K27ac. LINC01605 was found to bind to METTL3 and promote the m6A modification of SPTBN2 mRNA, thereby facilitating the translation of SPTBN2. METTL3/miR-1246/Sprouty-related, EVH1 domain-containing protein 2 (SPRED2) axis plays an important role in tumor metastasis and provides a new m6A modification pattern in Colorectal cancer development." M6ADIS0059 34544413; 31492150 . M6ACROT03591 REG00007 M6ATAR00109 Histone modification / Methylation EPIREG00071 EPITAR00204 EPITAR00489 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "LINC01605 was regulated by SMYD2-EP300-mediated modifications of histone Histone H3 lysine 4 trimethylation (H3K4me3) as well as H3K27ac. LINC01605 was found to bind to METTL3 and promote the m6A modification of SPTBN2 mRNA, thereby facilitating the translation of SPTBN2. METTL3/microRNA 1246 (MIR1246)/SPRED2 axis plays an important role in tumor metastasis and provides a new m6A modification pattern in Colorectal cancer development." M6ADIS0059 34544413; 31492150 . M6ACROT03592 REG00007 M6ATAR00208 Histone modification / Methylation EPIREG00071 EPITAR00204 EPITAR00489 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "LINC01605 was regulated by SMYD2-EP300-mediated modifications of histone Histone H3 lysine 4 trimethylation (H3K4me3) as well as H3K27ac. LINC01605 was found to bind to METTL3 and promote the m6A modification of SPTBN2 mRNA, thereby facilitating the translation of SPTBN2. METTL3 promotes colorectal cancer proliferation by stabilizing G1/S-specific cyclin-E1 (CCNE1) mRNA in an m6A-dependent manner, representing a promising therapeutic strategy for the treatment of CRC." M6ADIS0059 34544413; 32039568 . M6ACROT03593 REG00007 M6ATAR00283 Histone modification / Methylation EPIREG00071 EPITAR00204 EPITAR00489 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "LINC01605 was regulated by SMYD2-EP300-mediated modifications of histone Histone H3 lysine 4 trimethylation (H3K4me3) as well as H3K27ac. LINC01605 was found to bind to METTL3 and promote the m6A modification of SPTBN2 mRNA, thereby facilitating the translation of SPTBN2. METTL3 stabilizes Hexokinase-2 (HK2) and SLC2A1 (GLUT1) expression in colorectal cancer through an m6A-IGF2BP2/3- dependent mechanism." M6ADIS0059 34544413; 32245489 . M6ACROT03594 REG00007 M6ATAR00269 Histone modification / Methylation EPIREG00071 EPITAR00204 EPITAR00489 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "LINC01605 was regulated by SMYD2-EP300-mediated modifications of histone Histone H3 lysine 4 trimethylation (H3K4me3) as well as H3K27ac. LINC01605 was found to bind to METTL3 and promote the m6A modification of SPTBN2 mRNA, thereby facilitating the translation of SPTBN2. METTL3 stabilizes HK2 and Glucose transporter type 1 (SLC2A1) (GLUT1) expression in colorectal cancer through an m6A-IGF2BP2/3- dependent mechanism." M6ADIS0059 34544413; 32245489 . M6ACROT03595 REG00007 M6ATAR00341 Histone modification / Methylation EPIREG00071 EPITAR00204 EPITAR00489 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "LINC01605 was regulated by SMYD2-EP300-mediated modifications of histone Histone H3 lysine 4 trimethylation (H3K4me3) as well as H3K27ac. LINC01605 was found to bind to METTL3 and promote the m6A modification of SPTBN2 mRNA, thereby facilitating the translation of SPTBN2. METTL3 exerted its function through enhancing Myc proto-oncogene protein (MYC) expression, at least partially in an m6A-IGF2BP1-dependent manner. Knockdown of METTL3 suppressed colorectal cancer cell proliferation in vitro and in vivo." M6ADIS0059 34544413; 32509177 . M6ACROT03596 REG00007 M6ATAR00149 Histone modification / Methylation EPIREG00071 EPITAR00204 EPITAR00489 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "LINC01605 was regulated by SMYD2-EP300-mediated modifications of histone Histone H3 lysine 4 trimethylation (H3K4me3) as well as H3K27ac. LINC01605 was found to bind to METTL3 and promote the m6A modification of SPTBN2 mRNA, thereby facilitating the translation of SPTBN2. Overexpression of METTL3 upregulates Long intergenic non-protein coding RNA 2598 (LINC02598/RP11) expression in colorectal cancer cells. Overexpression of ALKBH5 downregulates RP11 expression." M6ADIS0059 34544413; 33335959 . M6ACROT03597 REG00007 M6ATAR00476 Histone modification / Methylation EPIREG00071 EPITAR00204 EPITAR00489 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "LINC01605 was regulated by SMYD2-EP300-mediated modifications of histone Histone H3 lysine 4 trimethylation (H3K4me3) as well as H3K27ac. LINC01605 was found to bind to METTL3 and promote the m6A modification of SPTBN2 mRNA, thereby facilitating the translation of SPTBN2. LINC00460 is a novel oncogene of colorectal cancer through interacting with IGF2BP2 and DHX9 and bind to the m6A modified High mobility group protein HMG-I/HMG-Y (HMGA1) mRNA to enhance the HMGA1 mRNA stability. The N6-methyladenosine (m6A) modification of HMGA1 mRNA by METTL3 enhanced HMGA1 expression in CRC." M6ADIS0059 34544413; 33526059 . M6ACROT03598 REG00007 M6ATAR00100 Histone modification / Methylation EPIREG00071 EPITAR00204 EPITAR00489 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "LINC01605 was regulated by SMYD2-EP300-mediated modifications of histone Histone H3 lysine 4 trimethylation (H3K4me3) as well as H3K27ac. LINC01605 was found to bind to METTL3 and promote the m6A modification of SPTBN2 mRNA, thereby facilitating the translation of SPTBN2. Long intergenic non-protein coding RNA 460 (LINC00460) is a novel oncogene of colorectal cancer through interacting with IGF2BP2 and DHX9 and bind to the m6A modified HMGA1 mRNA to enhance the HMGA1 mRNA stability. The N6-methyladenosine (m6A) modification of HMGA1 mRNA by METTL3 enhanced HMGA1 expression in CRC." M6ADIS0059 34544413; 33526059 . M6ACROT03599 REG00007 M6ATAR00036 Histone modification / Methylation EPIREG00071 EPITAR00204 EPITAR00489 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "LINC01605 was regulated by SMYD2-EP300-mediated modifications of histone Histone H3 lysine 4 trimethylation (H3K4me3) as well as H3K27ac. LINC01605 was found to bind to METTL3 and promote the m6A modification of SPTBN2 mRNA, thereby facilitating the translation of SPTBN2. METTL3-induced Circ_1662 promoted colorectal cancer cell invasion and migration by accelerating YAP1 nuclear transport. Circ1662 enhanced CRC invasion and migration depending on YAP1 and SMAD3. This result implies that circ1662 is a new prognostic and therapeutic marker for CRC metastasis." M6ADIS0059 34544413; 33754062 . M6ACROT03600 REG00007 M6ATAR00451 Histone modification / Methylation EPIREG00071 EPITAR00204 EPITAR00489 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "LINC01605 was regulated by SMYD2-EP300-mediated modifications of histone Histone H3 lysine 4 trimethylation (H3K4me3) as well as H3K27ac. LINC01605 was found to bind to METTL3 and promote the m6A modification of SPTBN2 mRNA, thereby facilitating the translation of SPTBN2. METTL3-induced circ1662 promoted colorectal cancer cell invasion and migration by accelerating Transcriptional coactivator YAP1 (YAP1) nuclear transport. Circ1662 enhanced CRC invasion and migration depending on YAP1 and SMAD3. This result implies that circ1662 is a new prognostic and therapeutic marker for CRC metastasis." M6ADIS0059 34544413; 33754062 . M6ACROT03601 REG00007 M6ATAR00396 Histone modification / Methylation EPIREG00071 EPITAR00204 EPITAR00489 Down regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "LINC01605 was regulated by SMYD2-EP300-mediated modifications of histone Histone H3 lysine 4 trimethylation (H3K4me3) as well as H3K27ac. LINC01605 was found to bind to METTL3 and promote the m6A modification of SPTBN2 mRNA, thereby facilitating the translation of SPTBN2. METTL3-induced circ1662 promoted colorectal cancer cell invasion and migration by accelerating YAP1 nuclear transport. Circ1662 enhanced CRC invasion and migration depending on YAP1 and Mothers against decapentaplegic homolog 3 (SMAD3). This result implies that circ1662 is a new prognostic and therapeutic marker for CRC metastasis." M6ADIS0059 34544413; 33754062 . M6ACROT03602 REG00007 M6ATAR00389 Histone modification / Methylation EPIREG00071 EPITAR00204 EPITAR00489 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "LINC01605 was regulated by SMYD2-EP300-mediated modifications of histone Histone H3 lysine 4 trimethylation (H3K4me3) as well as H3K27ac. LINC01605 was found to bind to METTL3 and promote the m6A modification of SPTBN2 mRNA, thereby facilitating the translation of SPTBN2. Translocation protein SEC62 (SEC62) upregulated by the METTL3-mediated m6A modification promotes the stemness and chemoresistance of colorectal cancer by binding to beta-catenin and enhancing Wnt signalling. Depletion of Sec62 sensitized the CRC cells to 5-Fu or oxaliplatin treatment." M6ADIS0059 34544413; 33858476 M6ADRUG0048 M6ACROT03603 REG00007 M6ATAR00389 Histone modification / Methylation EPIREG00071 EPITAR00204 EPITAR00489 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "LINC01605 was regulated by SMYD2-EP300-mediated modifications of histone Histone H3 lysine 4 trimethylation (H3K4me3) as well as H3K27ac. LINC01605 was found to bind to METTL3 and promote the m6A modification of SPTBN2 mRNA, thereby facilitating the translation of SPTBN2. Translocation protein SEC62 (SEC62) upregulated by the METTL3-mediated m6A modification promotes the stemness and chemoresistance of colorectal cancer by binding to beta-catenin and enhancing Wnt signalling. Depletion of Sec62 sensitized the CRC cells to 5-Fu or oxaliplatin treatment." M6ADIS0059 34544413; 33858476 M6ADRUG0005 M6ACROT03604 REG00007 M6ATAR00146 Histone modification / Methylation EPIREG00071 EPITAR00204 EPITAR00489 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "LINC01605 was regulated by SMYD2-EP300-mediated modifications of histone Histone H3 lysine 4 trimethylation (H3K4me3) as well as H3K27ac. LINC01605 was found to bind to METTL3 and promote the m6A modification of SPTBN2 mRNA, thereby facilitating the translation of SPTBN2. The increased LBX2 antisense RNA 1 (LBX2-AS1) in CRC was mediated by METTL3-dependent m6A methylation. LBX2-AS1 serves as a therapeutic target and predictor of 5-FU benefit in colorectal cancer patients." M6ADIS0059 34544413; 34535128 M6ADRUG0005 M6ACROT03605 REG00007 M6ATAR00377 Histone modification / Methylation EPIREG00071 EPITAR00204 EPITAR00489 Down regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "LINC01605 was regulated by SMYD2-EP300-mediated modifications of histone Histone H3 lysine 4 trimethylation (H3K4me3) as well as H3K27ac. LINC01605 was found to bind to METTL3 and promote the m6A modification of SPTBN2 mRNA, thereby facilitating the translation of SPTBN2. In colorectal cancer, n6-methyladenosine (m6A) subunit METTL3 increased PTTG3P expression by influencing its stability, while insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) could identify Putative pituitary tumor-transforming gene 3 protein (PTTG3P) m6A methylation status and bind to it." M6ADIS0059 34544413; 34660259 . M6ACROT03606 REG00007 M6ATAR00757 Histone modification / Methylation EPIREG00071 EPITAR00204 EPITAR00489 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "LINC01605 was regulated by SMYD2-EP300-mediated modifications of histone Histone H3 lysine 4 trimethylation (H3K4me3) as well as H3K27ac. LINC01605 was found to bind to METTL3 and promote the m6A modification of SPTBN2 mRNA, thereby facilitating the translation of SPTBN2. METTL3 promoted Class E basic helix-loop-helix protein 41 (BHLHE41) expression in m6A-dependent manner, which subsequently induced CXCL1 transcription to enhance MDSC migration in vitro. METTL3 as a potential therapeutic target for CRC immunotherapy whose inhibition reverses immune suppression through m6A-BHLHE41-CXCL1 axis." M6ADIS0059 34544413; 35700773 . M6ACROT03607 REG00007 M6ATAR00762 Histone modification / Methylation EPIREG00071 EPITAR00204 EPITAR00489 Down regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "LINC01605 was regulated by SMYD2-EP300-mediated modifications of histone Histone H3 lysine 4 trimethylation (H3K4me3) as well as H3K27ac. LINC01605 was found to bind to METTL3 and promote the m6A modification of SPTBN2 mRNA, thereby facilitating the translation of SPTBN2. m6A and METTL3 levels were substantially elevated in colorectal carcinoma(CRC) tissues, METTL3 knockdown substantially reduced the m6A level of Protein crumbs homolog 3 (CRB3), and inhibited the degradation of CRB3 mRNA to increase CRB3 expression. METTL3 regulated the progression of CRC by regulating the m6A-CRB3-Hippo pathway." M6ADIS0059 34544413; 35012593 . M6ACROT03608 REG00007 M6ATAR00771 Histone modification / Methylation EPIREG00071 EPITAR00204 EPITAR00489 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "LINC01605 was regulated by SMYD2-EP300-mediated modifications of histone Histone H3 lysine 4 trimethylation (H3K4me3) as well as H3K27ac. LINC01605 was found to bind to METTL3 and promote the m6A modification of SPTBN2 mRNA, thereby facilitating the translation of SPTBN2. METTL3 enhances the expression of Lactate dehydrogenase A (LDHA), which catalyzes the conversion of pyruvate to lactate, to trigger glycolysis and 5-FU resistance. METTL3/LDHA axis-induced glucose metabolism is a potential therapy target to overcome 5-FU resistance in CRC cells." M6ADIS0059 34544413; 35832094 . M6ACROT03609 REG00007 M6ATAR00773 Histone modification / Methylation EPIREG00071 EPITAR00204 EPITAR00489 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "LINC01605 was regulated by SMYD2-EP300-mediated modifications of histone Histone H3 lysine 4 trimethylation (H3K4me3) as well as H3K27ac. LINC01605 was found to bind to METTL3 and promote the m6A modification of SPTBN2 mRNA, thereby facilitating the translation of SPTBN2. METTL3 augmented 5 FU induced DNA damage and overcame 5 FU resistance in HCT 8R cells, which could be mimicked by inhibition of RAD51-associated protein 1 (RAD51AP1). The present study revealed that the METTL3/RAD51AP1 axis plays an important role in the acquisition of 5 FU resistance in CRC." M6ADIS0059 34544413; 35856434 M6ADRUG0005 M6ACROT03610 REG00007 M6ATAR01672 Histone modification / Methylation EPIREG00071 EPITAR00204 EPITAR00489 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "LINC01605 was regulated by SMYD2-EP300-mediated modifications of histone Histone H3 lysine 4 trimethylation (H3K4me3) as well as H3K27ac. LINC01605 was found to bind to METTL3 and promote the m6A modification of SPTBN2 mRNA, thereby facilitating the translation of SPTBN2. hsa_circ_0000677 and its downstream target ABCC1 were upregulated in CRC cells, induced by the METTL3-mediated m6A modification of circ_0000677 and SUMO1-mediated SUMOylation of METTL3. This work provided a new strategy for the therapeutic treatment of CRC." M6ADIS0059 34544413; 35030640 . M6ACROT03611 REG00007 M6ATAR00521 Histone modification / Methylation EPIREG00071 EPITAR00204 EPITAR00489 Down regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "LINC01605 was regulated by SMYD2-EP300-mediated modifications of histone Histone H3 lysine 4 trimethylation (H3K4me3) as well as H3K27ac. LINC01605 was found to bind to METTL3 and promote the m6A modification of SPTBN2 mRNA, thereby facilitating the translation of SPTBN2. In colorectal cancer, Mettl3- or Mettl14-deficient tumors increased cytotoxic tumor-infiltrating CD8+ T cells and elevated secretion of Interferon gamma (IFN-gamma), Cxcl9, and Cxcl10 in tumor microenvironment in vivo. Mechanistically, Mettl3 or Mettl14 loss promoted IFN-gamma-Stat1-Irf1 signaling through stabilizing the Stat1 and Irf1 mRNA via Ythdf2." M6ADIS0059 34544413; 32964498 . M6ACROT03612 REG00007 M6ATAR00522 Histone modification / Methylation EPIREG00071 EPITAR00204 EPITAR00489 Down regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "LINC01605 was regulated by SMYD2-EP300-mediated modifications of histone Histone H3 lysine 4 trimethylation (H3K4me3) as well as H3K27ac. LINC01605 was found to bind to METTL3 and promote the m6A modification of SPTBN2 mRNA, thereby facilitating the translation of SPTBN2. In colorectal cancer, Mettl3- or Mettl14-deficient tumors increased cytotoxic tumor-infiltrating CD8+ T cells and elevated secretion of IFN-gamma, C-X-C motif chemokine 9 (Cxcl9), and Cxcl10 in tumor microenvironment in vivo. Mechanistically, Mettl3 or Mettl14 loss promoted IFN-gamma-Stat1-Irf1 signaling through stabilizing the Stat1 and Irf1 mRNA via Ythdf2." M6ADIS0059 34544413; 32964498 . M6ACROT03613 REG00007 M6ATAR00523 Histone modification / Methylation EPIREG00071 EPITAR00204 EPITAR00489 Down regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "LINC01605 was regulated by SMYD2-EP300-mediated modifications of histone Histone H3 lysine 4 trimethylation (H3K4me3) as well as H3K27ac. LINC01605 was found to bind to METTL3 and promote the m6A modification of SPTBN2 mRNA, thereby facilitating the translation of SPTBN2. In colorectal cancer, Mettl3- or Mettl14-deficient tumors increased cytotoxic tumor-infiltrating CD8+ T cells and elevated secretion of IFN-gamma, Cxcl9, and C-X-C motif chemokine 10 (Cxcl10) in tumor microenvironment in vivo. Mechanistically, Mettl3 or Mettl14 loss promoted IFN-gamma-Stat1-Irf1 signaling through stabilizing the Stat1 and Irf1 mRNA via Ythdf2." M6ADIS0059 34544413; 32964498 . M6ACROT03614 REG00007 M6ATAR00524 Histone modification / Methylation EPIREG00071 EPITAR00204 EPITAR00489 Down regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "LINC01605 was regulated by SMYD2-EP300-mediated modifications of histone Histone H3 lysine 4 trimethylation (H3K4me3) as well as H3K27ac. LINC01605 was found to bind to METTL3 and promote the m6A modification of SPTBN2 mRNA, thereby facilitating the translation of SPTBN2. In colorectal cancer, Mettl3- or Mettl14-deficient tumors increased cytotoxic tumor-infiltrating CD8+ T cells and elevated secretion of IFN-gamma, Cxcl9, and Cxcl10 in tumor microenvironment in vivo. Mechanistically, Mettl3 or Mettl14 loss promoted IFN-gamma-Stat1-Irf1 signaling through stabilizing the Transcription factor ISGF-3 components p91/p84 (Stat1) and Irf1 mRNA via Ythdf2." M6ADIS0059 34544413; 32964498 . M6ACROT03615 REG00007 M6ATAR00525 Histone modification / Methylation EPIREG00071 EPITAR00204 EPITAR00489 Down regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "LINC01605 was regulated by SMYD2-EP300-mediated modifications of histone Histone H3 lysine 4 trimethylation (H3K4me3) as well as H3K27ac. LINC01605 was found to bind to METTL3 and promote the m6A modification of SPTBN2 mRNA, thereby facilitating the translation of SPTBN2. In colorectal cancer, Mettl3- or Mettl14-deficient tumors increased cytotoxic tumor-infiltrating CD8+ T cells and elevated secretion of IFN-gamma, Cxcl9, and Cxcl10 in tumor microenvironment in vivo. Mechanistically, Mettl3 or Mettl14 loss promoted IFN-gamma-Stat1-Irf1 signaling through stabilizing the Stat1 and Interferon regulatory factor 1 (Irf1) mRNA via Ythdf2." M6ADIS0059 34544413; 32964498 . M6ACROT03616 REG00007 M6ATAR00269 Histone modification / Methylation EPIREG00071 EPITAR00204 EPITAR00489 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "LINC01605 was regulated by SMYD2-EP300-mediated modifications of histone Histone H3 lysine 4 trimethylation (H3K4me3) as well as H3K27ac. LINC01605 was found to bind to METTL3 and promote the m6A modification of SPTBN2 mRNA, thereby facilitating the translation of SPTBN2. METTL3 induced Glucose transporter type 1 (SLC2A1) translation in an m6A-dependent manner, which subsequently promoted glucose uptake and lactate production, leading to the activation of mTORC1 signaling and CRC development. " M6ADIS0059 34544413; 33217448 . M6ACROT03617 REG00007 M6ATAR00399 Histone modification / Methylation EPIREG00071 EPITAR00204 EPITAR00489 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "LINC01605 was regulated by SMYD2-EP300-mediated modifications of histone Histone H3 lysine 4 trimethylation (H3K4me3) as well as H3K27ac. LINC01605 was found to bind to METTL3 and promote the m6A modification of SPTBN2 mRNA, thereby facilitating the translation of SPTBN2. METTL3 acts as a critical m6A methyltransferase capable of facilitating colorectal cancer(CRC) progression, and revealed a novel mechanism by which METTL3 promotes CRC cell proliferation and invasion via stabilizing Zinc finger protein SNAI1 (SNAI1) mRNA in an m6A-dependent manner. " M6ADIS0059 34544413; 34457066 . M6ACROT03618 REG00007 M6ATAR00663 Histone modification / Methylation EPIREG00071 EPITAR00204 EPITAR00489 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "LINC01605 was regulated by SMYD2-EP300-mediated modifications of histone Histone H3 lysine 4 trimethylation (H3K4me3) as well as H3K27ac. LINC01605 was found to bind to METTL3 and promote the m6A modification of SPTBN2 mRNA, thereby facilitating the translation of SPTBN2. METTL3 upregulated Urokinase-type plasminogen activator (PLAU) mRNA in an m6A-dependent manner, and then participated in MAPK/ERK pathway to promote angiogenesis and metastasis in CRC." M6ADIS0059 34544413; 35567945 . M6ACROT03619 REG00007 M6ATAR00666 Histone modification / Methylation EPIREG00071 EPITAR00204 EPITAR00489 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "LINC01605 was regulated by SMYD2-EP300-mediated modifications of histone Histone H3 lysine 4 trimethylation (H3K4me3) as well as H3K27ac. LINC01605 was found to bind to METTL3 and promote the m6A modification of SPTBN2 mRNA, thereby facilitating the translation of SPTBN2. METTL3 dependent m6A methylation was upregulated in CRC to promote the processing of miR 181d 5p by DGCR8. This led to increased hsa-miR-181d-5p expression, which inhibited the 5 FU sensitivity of CRC cells by targeting NCALD." M6ADIS0059 34544413; 35014676 M6ADRUG0005 M6ACROT03620 REG00007 M6ATAR00667 Histone modification / Methylation EPIREG00071 EPITAR00204 EPITAR00489 Down regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "LINC01605 was regulated by SMYD2-EP300-mediated modifications of histone Histone H3 lysine 4 trimethylation (H3K4me3) as well as H3K27ac. LINC01605 was found to bind to METTL3 and promote the m6A modification of SPTBN2 mRNA, thereby facilitating the translation of SPTBN2. METTL3 dependent m6A methylation was upregulated in CRC to promote the processing of miR 181d 5p by DGCR8. This led to increased miR 181d 5p expression, which inhibited the 5 FU sensitivity of CRC cells by targeting Neurocalcin-delta (NCALD)." M6ADIS0059 34544413; 35014676 M6ADRUG0005 M6ACROT03621 REG00007 M6ATAR00671 Histone modification / Methylation EPIREG00071 EPITAR00204 EPITAR00489 Down regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "LINC01605 was regulated by SMYD2-EP300-mediated modifications of histone Histone H3 lysine 4 trimethylation (H3K4me3) as well as H3K27ac. LINC01605 was found to bind to METTL3 and promote the m6A modification of SPTBN2 mRNA, thereby facilitating the translation of SPTBN2. 2-polarized tumor-associated macrophages enabled the oxaliplatin resistance via the elevation of METTL3-mediated m6A modification in Colorectal Cancer cells. Furthermore, they found that TNF receptor-associated factor 5 (TRAF5) contributes to the METTL3-triggered OX resistance in CRC cells." M6ADIS0059 34544413; 33555197 M6ADRUG0048 M6ACROT03622 REG00007 M6ATAR00680 Histone modification / Methylation EPIREG00071 EPITAR00204 EPITAR00489 Down regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "LINC01605 was regulated by SMYD2-EP300-mediated modifications of histone Histone H3 lysine 4 trimethylation (H3K4me3) as well as H3K27ac. LINC01605 was found to bind to METTL3 and promote the m6A modification of SPTBN2 mRNA, thereby facilitating the translation of SPTBN2. METTL3-catalyzed m6A modification in CRC tumorigenesis, wherein it facilitates CRC tumor growth and metastasis through suppressing Protein yippee-like 5 (YPEL5) expression in an m6A-YTHDF2-dependent manner." M6ADIS0059 34544413; 33411363 . M6ACROT03623 REG00007 M6ATAR00716 Histone modification / Methylation EPIREG00071 EPITAR00204 EPITAR00489 . Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "LINC01605 was regulated by SMYD2-EP300-mediated modifications of histone Histone H3 lysine 4 trimethylation (H3K4me3) as well as H3K27ac. LINC01605 was found to bind to METTL3 and promote the m6A modification of SPTBN2 mRNA, thereby facilitating the translation of SPTBN2. Ephrin type-A receptor 2 (EphA2) and VEGFA targeted by METTL3 via different IGF2BP-dependent mechanisms were found to promote vasculogenic mimicry (VM) formation via PI3K/AKT/mTOR and ERK1/2 signaling in CRC." M6ADIS0059 34544413; 35595748 . M6ACROT03624 REG00007 M6ATAR00446 Histone modification / Methylation EPIREG00071 EPITAR00204 EPITAR00489 . Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "LINC01605 was regulated by SMYD2-EP300-mediated modifications of histone Histone H3 lysine 4 trimethylation (H3K4me3) as well as H3K27ac. LINC01605 was found to bind to METTL3 and promote the m6A modification of SPTBN2 mRNA, thereby facilitating the translation of SPTBN2. EphA2 and Vascular endothelial growth factor A (VEGFA) targeted by METTL3 via different IGF2BP-dependent mechanisms were found to promote vasculogenic mimicry (VM) formation via PI3K/AKT/mTOR and ERK1/2 signaling in CRC." M6ADIS0059 34544413; 35595748 . M6ACROT03625 REG00007 M6ATAR01425 Histone modification / Methylation EPIREG00071 EPITAR00204 EPITAR00489 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "LINC01605 was regulated by SMYD2-EP300-mediated modifications of histone Histone H3 lysine 4 trimethylation (H3K4me3) as well as H3K27ac. LINC01605 was found to bind to METTL3 and promote the m6A modification of SPTBN2 mRNA, thereby facilitating the translation of SPTBN2. the malignant behaviors governed by Lithostathine-1-alpha (REG1A) could be effectively abolished by silencing of Wnt/beta-catenin/MYC axis or glycolysis process using specific inhibitors. Besides, REG1alpha expression was mediated by METTL3 in an m6A-dependent manner." M6ADIS0059 34544413; 37626036 . M6ACROT03626 REG00007 M6ATAR00836 Histone modification / Methylation EPIREG00071 EPITAR00204 EPITAR00489 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "LINC01605 was regulated by SMYD2-EP300-mediated modifications of histone Histone H3 lysine 4 trimethylation (H3K4me3) as well as H3K27ac. LINC01605 was found to bind to METTL3 and promote the m6A modification of SPTBN2 mRNA, thereby facilitating the translation of SPTBN2. Tl increased the level of aberrant N6-methyladenosine (m6A) modification of Polyamine-transporting ATPase 13A3 (ATP13A3) via the METLL3/METTL14/ALKBH5-ATP13A3 axis to promote colorectal tumorigenesis." M6ADIS0059 34544413; 36745568 . M6ACROT03627 REG00007 M6ATAR00117 Histone modification / Methylation EPIREG00071 EPITAR00204 EPITAR00489 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "LINC01605 was regulated by SMYD2-EP300-mediated modifications of histone Histone H3 lysine 4 trimethylation (H3K4me3) as well as H3K27ac. LINC01605 was found to bind to METTL3 and promote the m6A modification of SPTBN2 mRNA, thereby facilitating the translation of SPTBN2. METTL3 promotes proliferation and migration of colorectal cancer cells by increasing Small nucleolar RNA host gene 1 (SNHG1) stability" M6ADIS0059 34544413; 37772373 . M6ACROT03628 REG00007 M6ATAR00981 Histone modification / Methylation EPIREG00071 EPITAR00204 EPITAR00489 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "LINC01605 was regulated by SMYD2-EP300-mediated modifications of histone Histone H3 lysine 4 trimethylation (H3K4me3) as well as H3K27ac. LINC01605 was found to bind to METTL3 and promote the m6A modification of SPTBN2 mRNA, thereby facilitating the translation of SPTBN2. METTL3-Modulated Circ_UHRF2 Promotes Colorectal Cancer Stemness and Metastasis through Increasing DDX27 mRNA Stability by Recruiting IGF2BP1" M6ADIS0059 34544413; 37370759 . M6ACROT03629 REG00007 M6ATAR00982 Histone modification / Methylation EPIREG00071 EPITAR00204 EPITAR00489 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "LINC01605 was regulated by SMYD2-EP300-mediated modifications of histone Histone H3 lysine 4 trimethylation (H3K4me3) as well as H3K27ac. LINC01605 was found to bind to METTL3 and promote the m6A modification of SPTBN2 mRNA, thereby facilitating the translation of SPTBN2. The METTL3/IGF2BP2/Cohesin subunit SA-3 (STAG3) axis affects CRC progression in an m6A modification-dependent manner. This may guide targeted therapy in CRC patients." M6ADIS0059 34544413; 37828232 . M6ACROT03630 REG00007 M6ATAR01005 Histone modification / Methylation EPIREG00071 EPITAR00204 EPITAR00489 . Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "LINC01605 was regulated by SMYD2-EP300-mediated modifications of histone Histone H3 lysine 4 trimethylation (H3K4me3) as well as H3K27ac. LINC01605 was found to bind to METTL3 and promote the m6A modification of SPTBN2 mRNA, thereby facilitating the translation of SPTBN2. METTL3 regulates miR-196b expression via an N6-methyladenosine (m6A)-pri-miR-196b-dependent mechanism and thereby promotes CRC metastasis." M6ADIS0059 34544413; 36348020 . M6ACROT03631 REG00007 M6ATAR01058 Histone modification / Methylation EPIREG00071 EPITAR00204 EPITAR00489 Down regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "LINC01605 was regulated by SMYD2-EP300-mediated modifications of histone Histone H3 lysine 4 trimethylation (H3K4me3) as well as H3K27ac. LINC01605 was found to bind to METTL3 and promote the m6A modification of SPTBN2 mRNA, thereby facilitating the translation of SPTBN2. METTL3 mediated m6A methylation of hsa_circ_0124554.m6A-modified circ_0124554 promoted CRC progression and radioresistance by inducing LASP1 expression through interaction with miR-1184." M6ADIS0059 34544413; 38091882 . M6ACROT03632 REG00007 M6ATAR00561 Histone modification / Lactylation EPIREG00035 EPITAR00230 EPITAR00027 Up regulation Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "p300-mediated Histone H3 lysine 9 lactylation (H3K9la) in the promoter region of the N6-methyladenosine (m6A) writer METTL3 was enriched to enhance METTL3 transcription, leading to the lnc668 m6A modification. Meanwhile, the m6A reader YTHDC1 recognized m6A-modified lnc668 and elevated the METTL3-mediated lnc668 modification. Lowering m6A levels through silencing METTL3 suppresses the FMT process in vitro and in vivo. m6A modification regulates EMT by modulating the translation of Potassium voltage-gated channel subfamily H member 6 (KCNH6) mRNA in a YTHDF1-dependent manner. Manipulation of m6A modification through targeting METTL3 becomes a promising strategy for the treatment of idiopathic pulmonary fibrosis." M6ADIS0310 40221424; 34111558 . M6ACROT03633 REG00007 M6ATAR00696 Histone modification / Lactylation EPIREG00035 EPITAR00230 EPITAR00027 . Histone modification Direct Enhancement m6A histone modification directly impacts m6A modification through modulating the level of m6A regulator "p300-mediated Histone H3 lysine 9 lactylation (H3K9la) in the promoter region of the N6-methyladenosine (m6A) writer METTL3 was enriched to enhance METTL3 transcription, leading to the lnc668 m6A modification. Meanwhile, the m6A reader YTHDC1 recognized m6A-modified lnc668 and elevated the METTL3-mediated lnc668 modification. PM2.5 exposure increased the levels of METTL3-mediated m6A modification of Cadherin-1 (CDH1) mRNA. PM2.5 exposure triggered EMT progression to promote the pulmonary fibrosis via miR-494-3p/YTHDF2 recognized and METTL3 mediated m6A modification." M6ADIS0310 40221424; 34735003 . M6ACROT03634 REG00007 M6ATAR00196 Histone modification / Methylation EPIREG00036 EPITAR00205 EPITAR00490 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "Collectively, EZH2 downregulated hsa-miR-338-5p through Histone H3 lysine 27 trimethylation (H3K27me3), which in turn impaired miR-338-5p-dependent METTL3 inhibition and enhanced CDCP1 translation, therefore contributing to the development of GC. Down-regulation of METTL3 inhibits the proliferation and mobility of human gastric cancer cells and leads to inactivation of the AKT signaling pathway, suggesting that METTL3 is a potential target for the treatment of human gastric cancer. METTL3 knockdown decreased Apoptosis regulator Bcl-2 (BCL2) and increased Bax and active Caspase-3 in gastric cancer cells, which suggested the apoptotic pathway was activated. METTL3 led to inactivation of the AKT signaling pathway in human gastric cancer cells, including decreased phosphorylation levels of AKT and expression of down-stream effectors p70S6K and Cyclin D1. " M6ADIS0057 33882457; 30886897 . M6ACROT03635 REG00007 M6ATAR00195 Histone modification / Methylation EPIREG00036 EPITAR00205 EPITAR00490 Down regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "Collectively, EZH2 downregulated hsa-miR-338-5p through Histone H3 lysine 27 trimethylation (H3K27me3), which in turn impaired miR-338-5p-dependent METTL3 inhibition and enhanced CDCP1 translation, therefore contributing to the development of GC. Down-regulation of METTL3 inhibits the proliferation and mobility of human gastric cancer cells and leads to inactivation of the AKT signaling pathway, suggesting that METTL3 is a potential target for the treatment of human gastric cancer. METTL3 knockdown decreased Bcl2 and increased Apoptosis regulator BAX (BAX) and active Caspase-3 in gastric cancer cells, which suggested the apoptotic pathway was activated. METTL3 led to inactivation of the AKT signaling pathway in human gastric cancer cells, including decreased phosphorylation levels of AKT and expression of down-stream effectors p70S6K and Cyclin D1. " M6ADIS0057 33882457; 30886897 . M6ACROT03636 REG00007 M6ATAR00203 Histone modification / Methylation EPIREG00036 EPITAR00205 EPITAR00490 Down regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "Collectively, EZH2 downregulated hsa-miR-338-5p through Histone H3 lysine 27 trimethylation (H3K27me3), which in turn impaired miR-338-5p-dependent METTL3 inhibition and enhanced CDCP1 translation, therefore contributing to the development of GC. Down-regulation of METTL3 inhibits the proliferation and mobility of human gastric cancer cells and leads to inactivation of the AKT signaling pathway, suggesting that METTL3 is a potential target for the treatment of human gastric cancer. METTL3 knockdown decreased Bcl2 and increased Bax and active Caspase-3 (CASP3) in gastric cancer cells, which suggested the apoptotic pathway was activated. METTL3 led to inactivation of the AKT signaling pathway in human gastric cancer cells, including decreased phosphorylation levels of AKT and expression of down-stream effectors p70S6K and Cyclin D1. " M6ADIS0057 33882457; 30886897 . M6ACROT03637 REG00007 M6ATAR00175 Histone modification / Methylation EPIREG00036 EPITAR00205 EPITAR00490 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "Collectively, EZH2 downregulated hsa-miR-338-5p through Histone H3 lysine 27 trimethylation (H3K27me3), which in turn impaired miR-338-5p-dependent METTL3 inhibition and enhanced CDCP1 translation, therefore contributing to the development of GC. Down-regulation of METTL3 inhibits the proliferation and mobility of human gastric cancer cells and leads to inactivation of the AKT signaling pathway, suggesting that METTL3 is a potential target for the treatment of human gastric cancer. METTL3 knockdown decreased Bcl2 and increased Bax and active Caspase-3 in gastric cancer cells, which suggested the apoptotic pathway was activated. METTL3 led to inactivation of the AKT signaling pathway in human gastric cancer cells, including decreased phosphorylation levels of RAC-alpha serine/threonine-protein kinase (AKT1) and expression of down-stream effectors p70S6K and Cyclin D1. " M6ADIS0057 33882457; 30886897 . M6ACROT03638 REG00007 M6ATAR00313 Histone modification / Methylation EPIREG00036 EPITAR00205 EPITAR00490 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "Collectively, EZH2 downregulated hsa-miR-338-5p through Histone H3 lysine 27 trimethylation (H3K27me3), which in turn impaired miR-338-5p-dependent METTL3 inhibition and enhanced CDCP1 translation, therefore contributing to the development of GC. Down-regulation of METTL3 inhibits the proliferation and mobility of human gastric cancer cells and leads to inactivation of the AKT signaling pathway, suggesting that METTL3 is a potential target for the treatment of human gastric cancer. METTL3 knockdown decreased Bcl2 and increased Bax and active Caspase-3 in gastric cancer cells, which suggested the apoptotic pathway was activated. METTL3 led to inactivation of the AKT signaling pathway in human gastric cancer cells, including decreased phosphorylation levels of AKT and expression of down-stream effectors Ribosomal protein S6 kinase beta-1 (RPS6KB1/p70S6K) and Cyclin D1. " M6ADIS0057 33882457; 30886897 . M6ACROT03639 REG00007 M6ATAR00206 Histone modification / Methylation EPIREG00036 EPITAR00205 EPITAR00490 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "Collectively, EZH2 downregulated hsa-miR-338-5p through Histone H3 lysine 27 trimethylation (H3K27me3), which in turn impaired miR-338-5p-dependent METTL3 inhibition and enhanced CDCP1 translation, therefore contributing to the development of GC. Down-regulation of METTL3 inhibits the proliferation and mobility of human gastric cancer cells and leads to inactivation of the AKT signaling pathway, suggesting that METTL3 is a potential target for the treatment of human gastric cancer. METTL3 knockdown decreased Bcl2 and increased Bax and active Caspase-3 in gastric cancer cells, which suggested the apoptotic pathway was activated. METTL3 led to inactivation of the AKT signaling pathway in human gastric cancer cells, including decreased phosphorylation levels of AKT and expression of down-stream effectors p70S6K and G1/S-specific cyclin-D1 (CCND1). " M6ADIS0057 33882457; 30886897 . M6ACROT03640 REG00007 M6ATAR00795 Histone modification / Methylation EPIREG00036 EPITAR00205 EPITAR00490 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "Collectively, EZH2 downregulated hsa-miR-338-5p through Histone H3 lysine 27 trimethylation (H3K27me3), which in turn impaired miR-338-5p-dependent METTL3 inhibition and enhanced CDCP1 translation, therefore contributing to the development of GC. ARHGAP5-AS1 also stabilized ARHGAP5 mRNA in the cytoplasm by recruiting METTL3 to stimulate m6A modification of Rho GTPase activating protein 5 (ARHGAP5) mRNA. As a result, ARHGAP5 was upregulated to promote chemoresistance and its upregulation was also associated with poor prognosis in gastric cancer. downregulation of ARHGAP5-AS1 in resistant cells evidently reversed the resistance to chemotherapeutic drugs including cisplatin (DDP), ADM, and 5-FU." M6ADIS0057 33882457; 31097692 M6ADRUG0022 M6ACROT03641 REG00007 M6ATAR00795 Histone modification / Methylation EPIREG00036 EPITAR00205 EPITAR00490 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "Collectively, EZH2 downregulated hsa-miR-338-5p through Histone H3 lysine 27 trimethylation (H3K27me3), which in turn impaired miR-338-5p-dependent METTL3 inhibition and enhanced CDCP1 translation, therefore contributing to the development of GC. ARHGAP5-AS1 also stabilized ARHGAP5 mRNA in the cytoplasm by recruiting METTL3 to stimulate m6A modification of Rho GTPase activating protein 5 (ARHGAP5) mRNA. As a result, ARHGAP5 was upregulated to promote chemoresistance and its upregulation was also associated with poor prognosis in gastric cancer. downregulation of ARHGAP5-AS1 in resistant cells evidently reversed the resistance to chemotherapeutic drugs including cisplatin (DDP), ADM, and 5-FU." M6ADIS0057 33882457; 31097692 M6ADRUG0047 M6ACROT03642 REG00007 M6ATAR00795 Histone modification / Methylation EPIREG00036 EPITAR00205 EPITAR00490 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "Collectively, EZH2 downregulated hsa-miR-338-5p through Histone H3 lysine 27 trimethylation (H3K27me3), which in turn impaired miR-338-5p-dependent METTL3 inhibition and enhanced CDCP1 translation, therefore contributing to the development of GC. ARHGAP5-AS1 also stabilized ARHGAP5 mRNA in the cytoplasm by recruiting METTL3 to stimulate m6A modification of Rho GTPase activating protein 5 (ARHGAP5) mRNA. As a result, ARHGAP5 was upregulated to promote chemoresistance and its upregulation was also associated with poor prognosis in gastric cancer. downregulation of ARHGAP5-AS1 in resistant cells evidently reversed the resistance to chemotherapeutic drugs including cisplatin (DDP), ADM, and 5-FU." M6ADIS0057 33882457; 31097692 M6ADRUG0005 M6ACROT03643 REG00007 M6ATAR00170 Histone modification / Methylation EPIREG00036 EPITAR00205 EPITAR00490 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "Collectively, EZH2 downregulated hsa-miR-338-5p through Histone H3 lysine 27 trimethylation (H3K27me3), which in turn impaired miR-338-5p-dependent METTL3 inhibition and enhanced CDCP1 translation, therefore contributing to the development of GC. METTL3 knockdown decreased Actin, aortic smooth muscle (ACTA2) muscle actin. Taken together, our finding revealed that m6A methylation writer METTL3 serve as an oncogene in tumorigenesis of Gastric cancer." M6ADIS0057 33882457; 31232471 . M6ACROT03644 REG00007 M6ATAR00389 Histone modification / Methylation EPIREG00036 EPITAR00205 EPITAR00490 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "Collectively, EZH2 downregulated hsa-miR-338-5p through Histone H3 lysine 27 trimethylation (H3K27me3), which in turn impaired miR-338-5p-dependent METTL3 inhibition and enhanced CDCP1 translation, therefore contributing to the development of GC. miR-4429 prevented gastric cancer progression through targeting METTL3 to inhibit m6A-caused stabilization of Translocation protein SEC62 (SEC62), indicating miR-4429 as a promising target for treatment improvement for Gastric cancer. METTL3 interacted with SEC62 to induce the m6A on SEC62 mRNA, therefore facilitated the stabilizing effect of IGF2BP1 on SEC62 mRNA." M6ADIS0057 33882457; 31395342 . M6ACROT03645 REG00007 M6ATAR00271 Histone modification / Methylation EPIREG00036 EPITAR00205 EPITAR00490 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "Collectively, EZH2 downregulated hsa-miR-338-5p through Histone H3 lysine 27 trimethylation (H3K27me3), which in turn impaired miR-338-5p-dependent METTL3 inhibition and enhanced CDCP1 translation, therefore contributing to the development of GC. Elevated METTL3 expression promotes tumour angiogenesis and glycolysis in Gastric cancer. P300-mediated H3K27 acetylation activation in the promoter of METTL3 induced METTL3 transcription, which stimulated m6A modification of Hepatoma-derived growth factor (HDGF) mRNA, and the m6A reader IGF2BP3 then directly recognised and bound to the m6A site on HDGF mRNA and enhanced HDGF mRNA stability." M6ADIS0057 33882457; 31582403 . M6ACROT03646 REG00007 M6ATAR00454 Histone modification / Methylation EPIREG00036 EPITAR00205 EPITAR00490 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "Collectively, EZH2 downregulated hsa-miR-338-5p through Histone H3 lysine 27 trimethylation (H3K27me3), which in turn impaired miR-338-5p-dependent METTL3 inhibition and enhanced CDCP1 translation, therefore contributing to the development of GC. The m6A modification of Zinc finger MYM-type protein 1 (ZMYM1) mRNA by METTL3 enhanced its stability relying on the ""reader"" protein HuR (also known as ELAVL1) dependent pathway.The study uncover METTL3/ZMYM1/E-cadherin signaling as a potential therapeutic target in anti-metastatic strategy against Gastric cancer." M6ADIS0057 33882457; 31607270 . M6ACROT03647 REG00007 M6ATAR00157 Histone modification / Methylation EPIREG00036 EPITAR00205 EPITAR00490 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "Collectively, EZH2 downregulated hsa-miR-338-5p through Histone H3 lysine 27 trimethylation (H3K27me3), which in turn impaired miR-338-5p-dependent METTL3 inhibition and enhanced CDCP1 translation, therefore contributing to the development of GC. Long intergenic non-protein coding RNA 470 (LINC00470)-METTL3-mediated PTEN mRNA degradation relied on the m6A reader protein YTHDF2-dependent pathway.LINC00470 served as a therapeutic target for Gastric cancer patients." M6ADIS0057 33882457; 31711642 . M6ACROT03648 REG00007 M6ATAR00341 Histone modification / Methylation EPIREG00036 EPITAR00205 EPITAR00490 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "Collectively, EZH2 downregulated hsa-miR-338-5p through Histone H3 lysine 27 trimethylation (H3K27me3), which in turn impaired miR-338-5p-dependent METTL3 inhibition and enhanced CDCP1 translation, therefore contributing to the development of GC. In gastric cancer, several component molecules (e.g., MCM5, MCM6, etc.) of Myc proto-oncogene protein (MYC) target genes were mediated by METTL3 via altered m6A modification." M6ADIS0057 33882457; 32175271 . M6ACROT03649 REG00007 M6ATAR00321 Histone modification / Methylation EPIREG00036 EPITAR00205 EPITAR00490 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "Collectively, EZH2 downregulated hsa-miR-338-5p through Histone H3 lysine 27 trimethylation (H3K27me3), which in turn impaired miR-338-5p-dependent METTL3 inhibition and enhanced CDCP1 translation, therefore contributing to the development of GC. In gastric cancer, several component molecules (e.g., DNA replication licensing factor MCM5 (MCM5), MCM6, etc.) of MYC target genes were mediated by METTL3 via altered m6A modification." M6ADIS0057 33882457; 32175271 . M6ACROT03650 REG00007 M6ATAR00322 Histone modification / Methylation EPIREG00036 EPITAR00205 EPITAR00490 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "Collectively, EZH2 downregulated hsa-miR-338-5p through Histone H3 lysine 27 trimethylation (H3K27me3), which in turn impaired miR-338-5p-dependent METTL3 inhibition and enhanced CDCP1 translation, therefore contributing to the development of GC. In gastric cancer, several component molecules (e.g., MCM5, DNA replication licensing factor MCM6 (MCM6), etc.) of MYC target genes were mediated by METTL3 via altered m6A modification." M6ADIS0057 33882457; 32175271 . M6ACROT03651 REG00007 M6ATAR00341 Histone modification / Methylation EPIREG00036 EPITAR00205 EPITAR00490 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "Collectively, EZH2 downregulated hsa-miR-338-5p through Histone H3 lysine 27 trimethylation (H3K27me3), which in turn impaired miR-338-5p-dependent METTL3 inhibition and enhanced CDCP1 translation, therefore contributing to the development of GC. METTL3 enhanced Myc proto-oncogene protein (MYC) m6A methylation and increased MYC translation, which could potentiate the proliferation, migration and invasion of gastric cancer cells." M6ADIS0057 33882457; 33048840 . M6ACROT03652 REG00007 M6ATAR00102 Histone modification / Methylation EPIREG00036 EPITAR00205 EPITAR00490 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "Collectively, EZH2 downregulated hsa-miR-338-5p through Histone H3 lysine 27 trimethylation (H3K27me3), which in turn impaired miR-338-5p-dependent METTL3 inhibition and enhanced CDCP1 translation, therefore contributing to the development of GC. LV-sh-THAP7 antisense RNA 1 (THAP7-AS1) treatment could suppress gastric cancer growth. THAP7-AS1, transcriptionally activated by SP1 and then modified by METTL3-mediated m6A, exerts oncogenic functions, by promoting interaction between NLS and importin alpha-1 and then improving the CUL4B protein entry into the nucleus to repress the transcription of miR-22-3p and miR-320a. " M6ADIS0057 33882457; 34608273 . M6ACROT03653 REG00007 M6ATAR00714 Histone modification / Methylation EPIREG00036 EPITAR00205 EPITAR00490 Down regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "Collectively, EZH2 downregulated hsa-miR-338-5p through Histone H3 lysine 27 trimethylation (H3K27me3), which in turn impaired miR-338-5p-dependent METTL3 inhibition and enhanced CDCP1 translation, therefore contributing to the development of GC. METTL3 promotes translation of SPHK2 mRNA via an m6A-YTHDF1-dependent manner. Functionally, SPHK2 facilitates GC cell proliferation, migration and invasion by inhibiting Krueppel-like factor 2 (KLF2) expression." M6ADIS0057 33882457; 33758320 . M6ACROT03654 REG00007 M6ATAR00778 Histone modification / Methylation EPIREG00036 EPITAR00205 EPITAR00490 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "Collectively, EZH2 downregulated hsa-miR-338-5p through Histone H3 lysine 27 trimethylation (H3K27me3), which in turn impaired miR-338-5p-dependent METTL3 inhibition and enhanced CDCP1 translation, therefore contributing to the development of GC. METTL3 promotes translation of Sphingosine kinase 2 (SPHK2) mRNA via an m6A-YTHDF1-dependent manner. Functionally, SPHK2 facilitates GC cell proliferation, migration and invasion by inhibiting KLF2 expression." M6ADIS0057 33882457; 33758320 . M6ACROT03655 REG00007 M6ATAR00546 Histone modification / Methylation EPIREG00036 EPITAR00205 EPITAR00490 Down regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "Collectively, EZH2 downregulated hsa-miR-338-5p through Histone H3 lysine 27 trimethylation (H3K27me3), which in turn impaired miR-338-5p-dependent METTL3 inhibition and enhanced CDCP1 translation, therefore contributing to the development of GC. METTL3 facilitates GC progression through the A disintegrin and metalloproteinase with thrombospondin motifs 9 (ADAMTS9)-mediated PI3K/AKT pathway." M6ADIS0057 33882457; 35574388 . M6ACROT03656 REG00007 M6ATAR00551 Histone modification / Methylation EPIREG00036 EPITAR00205 EPITAR00490 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "Collectively, EZH2 downregulated hsa-miR-338-5p through Histone H3 lysine 27 trimethylation (H3K27me3), which in turn impaired miR-338-5p-dependent METTL3 inhibition and enhanced CDCP1 translation, therefore contributing to the development of GC. m6A methyltransferase METTL3 facilitates oxaliplatin resistance in CD133+ gastric cancer stem cells by Promoting Poly [ADP-ribose] polymerase 1 (PARP1) mRNA stability which increases base excision repair pathway activity. METTTL3 enhances the stability of PARP1 by recruiting YTHDF1 to target the 3'-untranslated Region (3'-UTR) of PARP1 mRNA." M6ADIS0057 33882457; 35179655 M6ADRUG0048 M6ACROT03657 REG00007 M6ATAR00552 Histone modification / Methylation EPIREG00036 EPITAR00205 EPITAR00490 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "Collectively, EZH2 downregulated hsa-miR-338-5p through Histone H3 lysine 27 trimethylation (H3K27me3), which in turn impaired miR-338-5p-dependent METTL3 inhibition and enhanced CDCP1 translation, therefore contributing to the development of GC. In gastric cancer, m6A facilitated processing of pri-miR-17-92 into the miR-17-92 cluster through an m6A/DGCR8-dependent mechanism. METTL3-high tumors showed preferred sensitivity to an mTOR inhibitor, everolimus." M6ADIS0057 33882457; 33037176 M6ADRUG0105 M6ACROT03658 REG00007 M6ATAR00451 Histone modification / Methylation EPIREG00036 EPITAR00205 EPITAR00490 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "Collectively, EZH2 downregulated hsa-miR-338-5p through Histone H3 lysine 27 trimethylation (H3K27me3), which in turn impaired miR-338-5p-dependent METTL3 inhibition and enhanced CDCP1 translation, therefore contributing to the development of GC. The expression of m6A and METTL3 was upregulated in human gastric cancer tissues and gastric cancer cell lines. m6A methyltransferase METTL3 promoted the proliferation and migration of gastric cancer cells through the m6A modification of Transcriptional coactivator YAP1 (YAP1)." M6ADIS0057 33882457; 34394353 . M6ACROT03659 REG00007 M6ATAR00401 Histone modification / Methylation EPIREG00036 EPITAR00205 EPITAR00490 Down regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "Collectively, EZH2 downregulated hsa-miR-338-5p through Histone H3 lysine 27 trimethylation (H3K27me3), which in turn impaired miR-338-5p-dependent METTL3 inhibition and enhanced CDCP1 translation, therefore contributing to the development of GC. METTL3-KO in gastric cancer cells resulted in the suppression of cell proliferation by inducing Suppressor of cytokine signaling 2 (SOCS2), suggesting a potential role of elevated METTL3 expression in gastric cancer progression." M6ADIS0057 33882457; 32782536 . M6ACROT03660 REG00007 M6ATAR00341 Histone modification / Methylation EPIREG00036 EPITAR00205 EPITAR00490 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "Collectively, EZH2 downregulated hsa-miR-338-5p through Histone H3 lysine 27 trimethylation (H3K27me3), which in turn impaired miR-338-5p-dependent METTL3 inhibition and enhanced CDCP1 translation, therefore contributing to the development of GC. Expressions of HBXIP, METTL3 and Myc proto-oncogene protein (MYC) were all determined to be upregulated in both GC tissues and cells. HBXIP plays an oncogenic role in GC via METTL3-mediated MYC mRNA m6A modification." M6ADIS0057 33882457; 33048840 . M6ACROT03661 REG00007 M6ATAR00741 Histone modification / Methylation EPIREG00036 EPITAR00205 EPITAR00490 Down regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "Collectively, EZH2 downregulated hsa-miR-338-5p through Histone H3 lysine 27 trimethylation (H3K27me3), which in turn impaired miR-338-5p-dependent METTL3 inhibition and enhanced CDCP1 translation, therefore contributing to the development of GC. N6-methyladenosine (m6A) modification of Basic leucine zipper transcriptional factor ATF-like 2 (BATF2) mRNA by METTL3 repressed its expression in gastric cancer." M6ADIS0057 33882457; 32650804 . M6ACROT03662 REG00007 M6ATAR00477 Histone modification / Methylation EPIREG00036 EPITAR00205 EPITAR00490 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "Collectively, EZH2 downregulated hsa-miR-338-5p through Histone H3 lysine 27 trimethylation (H3K27me3), which in turn impaired miR-338-5p-dependent METTL3 inhibition and enhanced CDCP1 translation, therefore contributing to the development of GC. METTL3-mediated m6A modification of lncRNA Small nucleolar RNA host gene 3 (SNHG3) accelerates GC progression by modulating miR-186-5p/cyclinD2 axis" M6ADIS0057 33882457; 37823387 . M6ACROT03663 REG00007 M6ATAR00704 Histone modification / Methylation EPIREG00036 EPITAR00205 EPITAR00490 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "Collectively, EZH2 downregulated hsa-miR-338-5p through Histone H3 lysine 27 trimethylation (H3K27me3), which in turn impaired miR-338-5p-dependent METTL3 inhibition and enhanced CDCP1 translation, therefore contributing to the development of GC. Depicting the Profile of METTL3-Mediated lncRNA m6A Modification Variants and Identified Small nucleolar RNA host gene (SNHG7) as a Prognostic Indicator of MNNG-Induced Gastric Cancer" M6ADIS0057 33882457; 37999596 . M6ACROT03664 REG00007 M6ATAR01496 Histone modification / Methylation EPIREG00036 EPITAR00205 EPITAR00490 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "Collectively, EZH2 downregulated hsa-miR-338-5p through Histone H3 lysine 27 trimethylation (H3K27me3), which in turn impaired miR-338-5p-dependent METTL3 inhibition and enhanced CDCP1 translation, therefore contributing to the development of GC. METTL3-mediated m6A modification promotes mRNA stability of Histone-lysine N-methyltransferase SUV39H2 (SUV39H2) in an IGF2BP2 dependent manner, resulting in upregulated mRNA expression of SUV39H2. As a histone methyltransferase, SUV39H2 was verified to increase the phosphorylation level of ATM through transcriptional repression of DUSP6, thereby promoting HRR and ultimately inhibiting GC chemosensitivity to cisplatin." M6ADIS0057 33882457; 36806557 . M6ACROT03665 REG00007 M6ATAR00418 Histone modification / Methylation EPIREG00036 EPITAR00205 EPITAR00490 . Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "Collectively, EZH2 downregulated hsa-miR-338-5p through Histone H3 lysine 27 trimethylation (H3K27me3), which in turn impaired miR-338-5p-dependent METTL3 inhibition and enhanced CDCP1 translation, therefore contributing to the development of GC. Mechanistically, AGAP2-AS1 bound WT1-associated protein (WTAP) to promote the formation of the WTAP/methyltransferase-like 3 (METTL3)/METTL14 m6A methyltransferase complex. AGAP2-AS1 stabilized signal transducer and activator of transcription 3 (Signal transducer and activator of transcription 3 (STAT3)) mRNA in an m6A-dependent manner and, thus, activated the interleukin 6 (IL6)/STAT3 pathway. Importantly, activation of the AGAP2-AS1/WTAP/STAT3 pathways promoted cell proliferation and migration in GC." M6ADIS0057 33882457; 37983949 . M6ACROT03666 REG00007 M6ATAR01091 Histone modification / Methylation EPIREG00036 EPITAR00205 EPITAR00490 Up regulation Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "Collectively, EZH2 downregulated hsa-miR-338-5p through Histone H3 lysine 27 trimethylation (H3K27me3), which in turn impaired miR-338-5p-dependent METTL3 inhibition and enhanced CDCP1 translation, therefore contributing to the development of GC. increased m6A modification of Centromere protein F (CENPF) was mediated by methyltransferase 3, and this modified molecule could be recognized by heterogeneous nuclear ribonucleoprotein A2/B1 (HNRNPA2B1), thereby promoting its mRNA stability.N6-methyladenosine modification of CENPF mRNA facilitates gastric cancer metastasis via regulating FAK nuclear export" M6ADIS0057 33882457; 37256823 . M6ACROT03667 REG00007 M6ATAR01375 Histone modification / Methylation EPIREG00036 EPITAR00205 EPITAR00490 . Histone modification Indirect Enhancement m6A histone modification indirectly regulates m6A modification through downstream signaling pathways "Collectively, EZH2 downregulated hsa-miR-338-5p through Histone H3 lysine 27 trimethylation (H3K27me3), which in turn impaired miR-338-5p-dependent METTL3 inhibition and enhanced CDCP1 translation, therefore contributing to the development of GC. miR-181-5p/Kelch-like protein 5 (KLHL5) could promote the proliferation, migration, and invasion of gastric cancer by activating m6A process through regulating METTL3." M6ADIS0057 33882457; 37733183 . M6ACROT05215 REG00001 M6ATAR01486 Histone modification / Acetylation EPIREG00067 EPITAR00203 EPITAR00179 Down regulation Histone modification Direct Inhibition m6A Histone modification directly impacts m6A modification through modulating the level of m6A regulator "HDACi reduces Ferroptosis suppressor protein 1 (AIFM2) by promoting its mRNA degradation. Specifically, it is confirmed that HDACi specifically targets HDAC1 and promotes the Histone H3 lysine 27 acetylation (H3K27ac) modification of fat mass- and obesity-associated gene (FTO) and AlkB Homolog 5, RNA Demethylase (ALKBH5), which results in significant activation of FTO and ALKBH5. The activation of FTO and ALKBH5 reduces N6-methyladenosine (m6A) modification on FSP1 mRNA, leading to its degradation in an IGF2BP1-dependent manner. Crucially, lactylation of HDAC1 K412 is essential for ferroptosis regulation. Both Vorinostat (SAHA) and Trichostatin A (TSA) notably diminish HDAC1 K412 lactylation in comparison to other HDAC1 inhibitors, exhibiting a consistent trend of increasing susceptibility to ferroptosis. " M6ADIS0059 39888307 M6ADRUG0258 M6ACROT05838 REG00007 M6ATAR01408 Histone modification / Propionylation . EPITAR00213 EPITAR00544 Up regulation m6A Indirect Enhancement Histone modification m6A modification indirectly regulates histone modification through downstream signaling pathways "RPN11 deubiquitinates and stabilizes METTL3 to enhance the m6A modification and expression of acyl-coenzyme A (CoA) synthetase short-chain family member 3 (Acyl-CoA synthetase short-chain family member 3, mitochondrial (ACSS3)), which generates propionyl-CoA to upregulate lipid metabolism genes (Acacb, FASN, Me1, Mid1ip1) via Histone H3 lysine 14 propionylation (H3K14pr). The RPN11-METTL3-ACSS3-histone propionylation pathway is activated in the livers of patients with NAFLD." M6ADIS0107 39146936 . M6ACROT05839 REG00007 M6ATAR01408 Histone modification / Propionylation . EPITAR00213 EPITAR00545 Up regulation m6A Indirect Enhancement Histone modification m6A modification indirectly regulates histone modification through downstream signaling pathways "RPN11 deubiquitinates and stabilizes METTL3 to enhance the m6A modification and expression of acyl-coenzyme A (CoA) synthetase short-chain family member 3 (Acyl-CoA synthetase short-chain family member 3, mitochondrial (ACSS3)), which generates propionyl-CoA to upregulate lipid metabolism genes (Acacb, Fasn, ME1, Mid1ip1) via Histone H3 lysine 14 propionylation (H3K14pr). The RPN11-METTL3-ACSS3-histone propionylation pathway is activated in the livers of patients with NAFLD." M6ADIS0107 39146936 . M6ACROT05840 REG00007 M6ATAR01408 Histone modification / Propionylation . EPITAR00213 EPITAR00546 Up regulation m6A Indirect Enhancement Histone modification m6A modification indirectly regulates histone modification through downstream signaling pathways "RPN11 deubiquitinates and stabilizes METTL3 to enhance the m6A modification and expression of acyl-coenzyme A (CoA) synthetase short-chain family member 3 (Acyl-CoA synthetase short-chain family member 3, mitochondrial (ACSS3)), which generates propionyl-CoA to upregulate lipid metabolism genes (Acacb, Fasn, Me1, MID1IP1) via Histone H3 lysine 14 propionylation (H3K14pr). The RPN11-METTL3-ACSS3-histone propionylation pathway is activated in the livers of patients with NAFLD." M6ADIS0107 39146936 . M6ACROT05841 REG00007 M6ATAR01408 Histone modification / Propionylation . EPITAR00214 EPITAR00544 Up regulation m6A Indirect Enhancement Histone modification m6A modification indirectly regulates histone modification through downstream signaling pathways "RPN11 deubiquitinates and stabilizes METTL3 to enhance the m6A modification and expression of acyl-coenzyme A (CoA) synthetase short-chain family member 3 (Acyl-CoA synthetase short-chain family member 3, mitochondrial (ACSS3)), which generates propionyl-CoA to upregulate lipid metabolism genes (Acacb, FASN, Me1, Mid1ip1) via Histone H3 lysine 23 propionylation (H3k23pr). The RPN11-METTL3-ACSS3-histone propionylation pathway is activated in the livers of patients with NAFLD." M6ADIS0107 39146936 . M6ACROT05842 REG00007 M6ATAR01408 Histone modification / Propionylation . EPITAR00214 EPITAR00545 Up regulation m6A Indirect Enhancement Histone modification m6A modification indirectly regulates histone modification through downstream signaling pathways "RPN11 deubiquitinates and stabilizes METTL3 to enhance the m6A modification and expression of acyl-coenzyme A (CoA) synthetase short-chain family member 3 (Acyl-CoA synthetase short-chain family member 3, mitochondrial (ACSS3)), which generates propionyl-CoA to upregulate lipid metabolism genes (Acacb, Fasn, ME1, Mid1ip1) via Histone H3 lysine 23 propionylation (H3k23pr). The RPN11-METTL3-ACSS3-histone propionylation pathway is activated in the livers of patients with NAFLD." M6ADIS0107 39146936 . M6ACROT05843 REG00007 M6ATAR01408 Histone modification / Propionylation . EPITAR00214 EPITAR00546 Up regulation m6A Indirect Enhancement Histone modification m6A modification indirectly regulates histone modification through downstream signaling pathways "RPN11 deubiquitinates and stabilizes METTL3 to enhance the m6A modification and expression of acyl-coenzyme A (CoA) synthetase short-chain family member 3 (Acyl-CoA synthetase short-chain family member 3, mitochondrial (ACSS3)), which generates propionyl-CoA to upregulate lipid metabolism genes (Acacb, Fasn, Me1, MID1IP1) via Histone H3 lysine 23 propionylation (H3k23pr). The RPN11-METTL3-ACSS3-histone propionylation pathway is activated in the livers of patients with NAFLD." M6ADIS0107 39146936 . M6ACROT05844 REG00005 M6ATAR01610 Histone modification / Acetylation EPIREG00058 EPITAR00203 EPITAR00548 Down regulation m6A Direct Inhibition Histone modification m6A modification impacts directly histone modification through modulating the expression level of histone-associated enzymes "Demethylase ALKBH5 was found to reduce m6A methylation levels on Histone acetyltransferase KAT2A (KAT2A) mRNA, leading to its upregulation. YTHDF2 played a crucial role as an m6A reader protein mediating the degradation of Kat2a mRNA. Furthermore, Kat2a promoted ferroptosis by increasing Tfrc and HMOX1 expression via enhancing the enrichment of Histone H3 lysine 27 acetylation (H3K27ac) and H3K9ac on their promoter regions. In conclusion, our findings unveil a novel role for the Kat2a-ferroptosis axis in DCM pathogenesis, providing valuable insights for potential clinical interventions." M6ADIS0142 38858351 . M6ACROT05845 REG00008 M6ATAR01610 Histone modification / Acetylation EPIREG00058 EPITAR00203 EPITAR00548 Up regulation m6A Direct Enhancement Histone modification m6A modification impacts directly histone modification through modulating the expression level of histone-associated enzymes "Demethylase ALKBH5 was found to reduce m6A methylation levels on Histone acetyltransferase KAT2A (KAT2A) mRNA, leading to its upregulation. YTHDF2 played a crucial role as an m6A reader protein mediating the degradation of Kat2a mRNA. Furthermore, Kat2a promoted ferroptosis by increasing Tfrc and HMOX1 expression via enhancing the enrichment of Histone H3 lysine 27 acetylation (H3K27ac) and H3K9ac on their promoter regions. In conclusion, our findings unveil a novel role for the Kat2a-ferroptosis axis in DCM pathogenesis, providing valuable insights for potential clinical interventions." M6ADIS0142 38858351 . M6ACROT05846 REG00005 M6ATAR01610 Histone modification / Acetylation EPIREG00058 EPITAR00209 EPITAR00548 Down regulation m6A Direct Inhibition Histone modification m6A modification impacts directly histone modification through modulating the expression level of histone-associated enzymes "Demethylase ALKBH5 was found to reduce m6A methylation levels on Histone acetyltransferase KAT2A (KAT2A) mRNA, leading to its upregulation. YTHDF2 played a crucial role as an m6A reader protein mediating the degradation of Kat2a mRNA. Furthermore, Kat2a promoted ferroptosis by increasing Tfrc and HMOX1 expression via enhancing the enrichment of H3K27ac and Histone H3 lysine 9 acetylation (H3K9ac) on their promoter regions. In conclusion, our findings unveil a novel role for the Kat2a-ferroptosis axis in DCM pathogenesis, providing valuable insights for potential clinical interventions." M6ADIS0142 38858351 . M6ACROT05847 REG00008 M6ATAR01610 Histone modification / Acetylation EPIREG00058 EPITAR00209 EPITAR00548 Up regulation m6A Direct Enhancement Histone modification m6A modification impacts directly histone modification through modulating the expression level of histone-associated enzymes "Demethylase ALKBH5 was found to reduce m6A methylation levels on Histone acetyltransferase KAT2A (KAT2A) mRNA, leading to its upregulation. YTHDF2 played a crucial role as an m6A reader protein mediating the degradation of Kat2a mRNA. Furthermore, Kat2a promoted ferroptosis by increasing Tfrc and HMOX1 expression via enhancing the enrichment of H3K27ac and Histone H3 lysine 9 acetylation (H3K9ac) on their promoter regions. In conclusion, our findings unveil a novel role for the Kat2a-ferroptosis axis in DCM pathogenesis, providing valuable insights for potential clinical interventions." M6ADIS0142 38858351 . M6ACROT05848 REG00007 M6ATAR01616 Histone modification / Acetylation EPIREG00064 EPITAR00203 EPITAR00550 Up regulation m6A Indirect Enhancement Histone modification m6A modification indirectly regulates histone modification through downstream signaling pathways "Mechanistically, Histone-lysine N-methyltransferase SETMAR (SETMAR) methylates H3K36me2 in the SMARCA2 promoter region to promote SMARCA2 transcription. SMARCA2 can increase Histone H3 lysine 27 acetylation (H3K27ac) enrichment and bind to enhancers of the thyroid differentiation transcription factors (PAX8 and FOXE1) to promote their expression by enhancing chromatin accessibility. Moreover, METTL3-mediated m6A methylation of SETAMR mRNA is observed and showed that this medication can affect SETMAR expression in an IGF2BP3-dependent manner. " M6ADIS0073 38900084 . M6ACROT05849 REG00014 M6ATAR01616 Histone modification / Acetylation EPIREG00064 EPITAR00203 EPITAR00550 Up regulation m6A Indirect Enhancement Histone modification m6A modification indirectly regulates histone modification through downstream signaling pathways "Mechanistically, Histone-lysine N-methyltransferase SETMAR (SETMAR) methylates H3K36me2 in the SMARCA2 promoter region to promote SMARCA2 transcription. SMARCA2 can increase Histone H3 lysine 27 acetylation (H3K27ac) enrichment and bind to enhancers of the thyroid differentiation transcription factors (PAX8 and FOXE1) to promote their expression by enhancing chromatin accessibility. Moreover, METTL3-mediated m6A methylation of SETAMR mRNA is observed and showed that this medication can affect SETMAR expression in an IGF2BP3-dependent manner. " M6ADIS0073 38900084 . M6ACROT05850 REG00012 M6ATAR01486 Histone modification / Acetylation EPIREG00067 EPITAR00203 EPITAR00183 Up regulation Histone modification Indirect Enhancement m6A Histone modification indirectly regulates m6A modification through downstream signaling pathways "HDACi reduces Ferroptosis suppressor protein 1 (AIFM2) by promoting its mRNA degradation. Specifically, it is confirmed that HDACi specifically targets HDAC1 and promotes the Histone H3 lysine 27 acetylation (H3K27ac) modification of fat mass- and obesity-associated gene (FTO) and AlkB Homolog 5, RNA Demethylase (ALKBH5), which results in significant activation of FTO and ALKBH5. The activation of FTO and ALKBH5 reduces N6-methyladenosine (m6A) modification on FSP1 mRNA, leading to its degradation in an IGF2BP1-dependent manner. Crucially, lactylation of HDAC1 K412 is essential for ferroptosis regulation. Both Vorinostat (SAHA) and Trichostatin A (TSA) notably diminish HDAC1 K412 lactylation in comparison to other HDAC1 inhibitors, exhibiting a consistent trend of increasing susceptibility to ferroptosis. " M6ADIS0059 39888307 M6ADRUG0261 M6ACROT05851 REG00007 M6ATAR00990 Histone modification / Methylation EPIREG00079 EPITAR00204 EPITAR00552 Up regulation m6A Direct Enhancement Histone modification m6A modification impacts directly histone modification through modulating the expression level of histone-associated enzymes "METTL3 promoted the expression of Histone-lysine N-methyltransferase ASH1L (ASH1L) via enhancing its stability in a YT521-B homology domain containing 2 (YTHDC2)-dependent manner, which further decreased the expression of IL-17 and IL-23 receptor (IL23R) by modulating Histone H3 lysine 4 trimethylation (H3K4me3) levels, resulting in reduced pathogenic Th17 responses." M6ADIS0182 36753389 . M6ACROT05852 REG00023 M6ATAR00990 Histone modification / Methylation EPIREG00079 EPITAR00204 EPITAR00552 Up regulation m6A Direct Enhancement Histone modification m6A modification impacts directly histone modification through modulating the expression level of histone-associated enzymes "METTL3 promoted the expression of Histone-lysine N-methyltransferase ASH1L (ASH1L) via enhancing its stability in a YT521-B homology domain containing 2 (YTHDC2)-dependent manner, which further decreased the expression of IL-17 and IL-23 receptor (IL23R) by modulating Histone H3 lysine 4 trimethylation (H3K4me3) levels, resulting in reduced pathogenic Th17 responses." M6ADIS0182 36753389 . M6ACROT05853 REG00012 M6ATAR01012 Histone modification / Acetylation EPIREG00067 EPITAR00203 EPITAR00183 . Histone modification Indirect Enhancement m6A Histone modification indirectly regulates m6A modification through downstream signaling pathways "HDACi reduces ferroptosis suppressor protein (FSP1) by promoting its mRNA degradation. Specifically, it is confirmed that HDACi specifically targets HDAC1 and promotes the Histone H3 lysine 27 acetylation (H3K27ac) modification of fat mass- and obesity-associated gene (FTO) and AlkB Homolog 5, RNA Demethylase (ALKBH5), which results in significant activation of FTO and ALKBH5. The activation of FTO and ALKBH5 reduces N6-methyladenosine (m6A) modification on FSP1 mRNA, leading to its degradation. Crucially, lactylation of HDAC1K412is essential for ferroptosis regulation. Both Vorinostat (SAHA) and Trichostatin A (TSA) notably diminish HDAC1K412lactylation in comparison to other HDAC1 inhibitors, exhibiting a consistent trend of increasing susceptibility to ferroptosis. METTL14/ALKBH5/IGF2BP1 combine to modulate JmjC domain-containing protein 8 (JMJD8) stability in an m6A-dependent manner, which increases glycolysis and accelerates the development of CRC by enhancing the enzymatic activity of PKM2." M6ADIS0059 39888307; 37310898 . M6ACROT05863 REG00012 M6ATAR00341 Histone modification / Methylation EPIREG00036 EPITAR00205 EPITAR00515 Up regulation Histone modification Indirect Inhibition m6A Histone modification indirectly regulates m6A modification through downstream signaling pathways "Mechanistically, downregulation of LINC00261 was caused by hypermethylation of the CpG island in the promoter region and EZH2-mediated Histone H3 lysine 27 trimethylation (H3K27me3). LINC00261 exerted its biological function by binding to miR-222-3p to activate the HIPK2/ERK/Myc proto-oncogene protein (MYC) pathway. LINC00261 could also reduce c-myc expression by sequestering IGF2BP1." M6ADIS0061 33122827 . M6ACROT05868 REG00023 M6ATAR00961 Histone modification / Methylation EPIREG00039 EPITAR00204 . . m6A Direct Enhancement Histone modification m6A modification directly impacts histone modification through recruiting histone-associated enzymes "Cofilin family protein CFL1, overexpressed in PDAC, as a METTL3 cofactor that helps seRNA m6A methylation formation. The increased seRNA m6As are recognized by the reader YTHDC2, which recruits H3K4 methyltransferase KMT2A to promote Histone H3 lysine 4 trimethylation (H3K4me3) modification cotranscriptionally. Super-enhancers with a high level of H3K4me3 augment chromatin accessibility and facilitate oncogene transcription." M6ADIS0061 37957340 . M6ACROT05951 REG00001 M6ATAR00150 Histone modification / Methylation EPIREG00036 EPITAR00205 EPITAR00500 Down regulation m6A Indirect Inhibition Histone modification m6A modification indirectly regulates histone modification through downstream signaling pathways "The expression of the m6A demethylase FTO protein was significantly increased, which led to the inhibition of the Maternally expressed 3 (MEG3) m6A modification and weakened the stabilizing effect of the m6A binding protein YTHDC1 on MEG3. Additionally, it was found that MEG3 could bind simultaneously with the EZH2 protein and the TGFB1 gene promoter. This enabled the localization of the EZH2 protein to the TGF-beta1 gene promoter, where it induced Histone H3 lysine 27 trimethylation (H3K27me3) modification, thereby inhibiting the transcription of the TGFB1 gene." M6ADIS0361 38245815 . M6ACROT05952 REG00022 M6ATAR00150 Histone modification / Methylation EPIREG00036 EPITAR00205 EPITAR00500 Up regulation m6A Indirect Enhancement Histone modification m6A modification indirectly regulates histone modification through downstream signaling pathways "The expression of the m6A demethylase FTO protein was significantly increased, which led to the inhibition of the Maternally expressed 3 (MEG3) m6A modification and weakened the stabilizing effect of the m6A binding protein YTHDC1 on MEG3. Additionally, it was found that MEG3 could bind simultaneously with the EZH2 protein and the TGFB1 gene promoter. This enabled the localization of the EZH2 protein to the TGF-beta1 gene promoter, where it induced Histone H3 lysine 27 trimethylation (H3K27me3) modification, thereby inhibiting the transcription of the TGFB1 gene." M6ADIS0361 38245815 . M6ACROT05953 REG00050 M6ATAR01836 Histone modification / Methylation EPIREG00050 EPITAR00205 . Down regulation m6A Indirect Enhancement Histone modification m6A modification indirectly regulates histone modification through downstream signaling pathways "RBFOX2 can recruit RBM15, an MTC component, to facilitate methylation of Chromatin-associated RNAs (caRNAs). RBM15 also physically interacts with YTHDC1 and recruits polycomb repressive complex 2 (PRC2) to the RBFOX2-bound loci for chromatin silencing and transcription suppression. PRC2, a key player in epigenetic regulation, is known to mediate the trimethylation of histone H3 on lysine 27 (Histone H3 lysine 27 trimethylation (H3K27me3)). This modification is crucial for the establishment of a repressive chromatin state, effectively preventing the binding of transcriptional activators and thus suppressing gene expression at the loci targeted by RBFOX2 and its associated factors. RBFOX2/m6A/RBM15/YTHDC1/PRC2 axis plays a critical role in myeloid leukaemia. " M6ADIS0004 37640841 . M6ACROT05954 REG00020 M6ATAR01836 Histone modification / Methylation EPIREG00050 EPITAR00205 . Down regulation m6A Indirect Enhancement Histone modification m6A modification indirectly regulates histone modification through downstream signaling pathways "RBFOX2 can recruit RBM15, an MTC component, to facilitate methylation of Chromatin-associated RNAs (caRNAs). RBM15 also physically interacts with YTHDC1 and recruits polycomb repressive complex 2 (PRC2) to the RBFOX2-bound loci for chromatin silencing and transcription suppression. PRC2, a key player in epigenetic regulation, is known to mediate the trimethylation of histone H3 on lysine 27 (Histone H3 lysine 27 trimethylation (H3K27me3)). This modification is crucial for the establishment of a repressive chromatin state, effectively preventing the binding of transcriptional activators and thus suppressing gene expression at the loci targeted by RBFOX2 and its associated factors. RBFOX2/m6A/RBM15/YTHDC1/PRC2 axis plays a critical role in myeloid leukaemia. " M6ADIS0004 37640841 . M6ACROT05955 REG00022 M6ATAR01836 Histone modification / Methylation EPIREG00050 EPITAR00205 . Down regulation m6A Direct Enhancement Histone modification m6A modification directly impacts histone modification through recruiting histone-associated enzymes "RBFOX2 can recruit RBM15, an MTC component, to facilitate methylation of Chromatin-associated RNAs (caRNAs). RBM15 also physically interacts with YTHDC1 and recruits polycomb repressive complex 2 (PRC2) to the RBFOX2-bound loci for chromatin silencing and transcription suppression. PRC2, a key player in epigenetic regulation, is known to mediate the trimethylation of histone H3 on lysine 27 (Histone H3 lysine 27 trimethylation (H3K27me3)). This modification is crucial for the establishment of a repressive chromatin state, effectively preventing the binding of transcriptional activators and thus suppressing gene expression at the loci targeted by RBFOX2 and its associated factors. RBFOX2/m6A/RBM15/YTHDC1/PRC2 axis plays a critical role in myeloid leukaemia. " M6ADIS0004 37640841 . M6ACROT05956 REG00005 M6ATAR00707 Histone modification / Methylation EPIREG00090 EPITAR00502 . Up regulation Histone modification Indirect Enhancement m6A Histone modification indirectly regulates m6A modification through downstream signaling pathways "PRMT5 inhibited doxorubicin-induced RNA m6A methylation by enhancing the nuclear translocation of ALKBH5 with the partner Alpha-ketoglutarate-dependent dioxygenase alkB homolog 7, mitochondrial (ALKBH7). ALKBH5 removed m6A methylation from Breast cancer type 1 susceptibility protein (BRCA1) mRNA, maintained BRCA1 stability and function, and thereby reduced cell sensitivity to doxorubicin. The approved drug tadalafil as a novel PRMT5 inhibitor that could decrease RNA m6A methylation and increase doxorubicin sensitivity in breast cancer. " M6ADIS0065 35278676 M6ADRUG0022 M6ACROT05957 REG00005 M6ATAR00707 Histone modification / Methylation EPIREG00090 EPITAR00502 . Up regulation Histone modification Indirect Enhancement m6A Histone modification indirectly regulates m6A modification through downstream signaling pathways "PRMT5 inhibited doxorubicin-induced RNA m6A methylation by enhancing the nuclear translocation of ALKBH5 with the partner Alpha-ketoglutarate-dependent dioxygenase alkB homolog 7, mitochondrial (ALKBH7). ALKBH5 removed m6A methylation from Breast cancer type 1 susceptibility protein (BRCA1) mRNA, maintained BRCA1 stability and function, and thereby reduced cell sensitivity to doxorubicin. The approved drug tadalafil as a novel PRMT5 inhibitor that could decrease RNA m6A methylation and increase doxorubicin sensitivity in breast cancer. " M6ADIS0065 35278676 M6ADRUG0257 M6ACROT05973 REG00009 M6ATAR00784 Histone modification / Methylation EPIREG00055 EPITAR00204 EPITAR00269 Down regulation Histone modification Direct Inhibition m6A Histone modification directly impacts m6A modification through modulating the level of m6A regulator "LncRNA Long intergenic non-protein coding RNA 657 (NORAD) could be modified by m6A due to an increase in WTAP, which was regulated by KDM5A-mediated Histone H3 lysine 4 trimethylation (H3K4me3) modification of the promoter. YTHDF2-mediated decay of NORAD is enhanced in senescent NPCs, and then deficiency of NORAD results in less sequestraion of PUMILIO proteins, contributing to the augmented activity of PUM1 and PUM2, thus repressing the expression of target E2F3 mRNAs and promoting the cellular senescence." M6ADIS0168 35304463 . M6ACROT05974 REG00008 M6ATAR00784 Histone modification / Methylation EPIREG00055 EPITAR00204 EPITAR00269 Down regulation Histone modification Indirect Inhibition m6A Histone modification indirectly regulates m6A modification through downstream signaling pathways "LncRNA Long intergenic non-protein coding RNA 657 (NORAD) could be modified by m6A due to an increase in WTAP, which was regulated by KDM5A-mediated Histone H3 lysine 4 trimethylation (H3K4me3) modification of the promoter. YTHDF2-mediated decay of NORAD is enhanced in senescent NPCs, and then deficiency of NORAD results in less sequestraion of PUMILIO proteins, contributing to the augmented activity of PUM1 and PUM2, thus repressing the expression of target E2F3 mRNAs and promoting the cellular senescence." M6ADIS0168 35304463 . M6ACROT05995 REG00008 M6ATAR01264 Histone modification / Methylation EPIREG00037 EPITAR00205 EPITAR00560 Down regulation m6A Direct Inhibition Histone modification m6A modification impacts directly histone modification through modulating the expression level of histone-associated enzymes "The mRNA of Lysine-specific demethylase 6B (KDM6B) was m6A-modified by METTL3/METTL14 and its decay mediated by YTHDF2. YTHDF2 deficiency stabilized KDM6B to promote Histone H3 lysine 27 trimethylation (H3K27me3) demethylation of multiple proinflammatory cytokines and subsequently enhanced their transcription. Knockout (KO) of YTHDF2, an m6A reader, markedly enhanced demethylation of H3K27me3 on the promoters of proinflammatory cytokines (e.g., IL-6 and IL12B). Furthermore, we identified H3K27me3 as a barrier for m6A modification during transcription. KDM6B recruits the m6A methyltransferase complex to facilitate the methylation of m6A in transcribing mRNA by removing adjacent H3K27me3 barriers. These results revealed cross-talk between m6A and H3K27me3 during bacterial infection, which has broader implications for deciphering epitranscriptomics in immune homeostasis." M6ADIS0125 32875102 . M6ACROT05996 REG00007 M6ATAR01264 Histone modification / Methylation EPIREG00037 EPITAR00205 EPITAR00560 Down regulation m6A Direct Inhibition Histone modification m6A modification impacts directly histone modification through modulating the expression level of histone-associated enzymes "The mRNA of Lysine-specific demethylase 6B (KDM6B) was m6A-modified by METTL3/METTL14 and its decay mediated by YTHDF2. YTHDF2 deficiency stabilized KDM6B to promote Histone H3 lysine 27 trimethylation (H3K27me3) demethylation of multiple proinflammatory cytokines and subsequently enhanced their transcription. Knockout (KO) of YTHDF2, an m6A reader, markedly enhanced demethylation of H3K27me3 on the promoters of proinflammatory cytokines (e.g., IL-6 and IL12B). Furthermore, we identified H3K27me3 as a barrier for m6A modification during transcription. KDM6B recruits the m6A methyltransferase complex to facilitate the methylation of m6A in transcribing mRNA by removing adjacent H3K27me3 barriers. These results revealed cross-talk between m6A and H3K27me3 during bacterial infection, which has broader implications for deciphering epitranscriptomics in immune homeostasis." M6ADIS0125 32875102 . M6ACROT05997 REG00006 M6ATAR01264 Histone modification / Methylation EPIREG00037 EPITAR00205 EPITAR00560 Down regulation m6A Direct Inhibition Histone modification m6A modification impacts directly histone modification through modulating the expression level of histone-associated enzymes "The mRNA of Lysine-specific demethylase 6B (KDM6B) was m6A-modified by METTL3/METTL14 and its decay mediated by YTHDF2. YTHDF2 deficiency stabilized KDM6B to promote Histone H3 lysine 27 trimethylation (H3K27me3) demethylation of multiple proinflammatory cytokines and subsequently enhanced their transcription. Knockout (KO) of YTHDF2, an m6A reader, markedly enhanced demethylation of H3K27me3 on the promoters of proinflammatory cytokines (e.g., IL-6 and IL12B). Furthermore, we identified H3K27me3 as a barrier for m6A modification during transcription. KDM6B recruits the m6A methyltransferase complex to facilitate the methylation of m6A in transcribing mRNA by removing adjacent H3K27me3 barriers. These results revealed cross-talk between m6A and H3K27me3 during bacterial infection, which has broader implications for deciphering epitranscriptomics in immune homeostasis." M6ADIS0125 32875102 . M6ACROT05998 REG00009 M6ATAR01838 Histone modification / Methylation EPIREG00037 EPITAR00205 EPITAR00560 . Histone modification Direct Enhancement m6A Histone modification directly impacts m6A modification through recruiting m6A regulator "Knockout (KO) of YTHDF2, an m6A reader, markedly enhanced demethylation of Histone H3 lysine 27 trimethylation (H3K27me3) on the promoters of proinflammatory cytokines (e.g., IL-6 and Interleukin-12 subunit beta (IL12B)). Furthermore, we identified H3K27me3 as a barrier for m6A modification during transcription. KDM6B recruits the m6A methyltransferase complex (METTL3/METTL14/WTAP) to facilitate the methylation of m6A in transcribing mRNA by removing adjacent H3K27me3 barriers. These results revealed cross-talk between m6A and H3K27me3 during bacterial infection, which has broader implications for deciphering epitranscriptomics in immune homeostasis." M6ADIS0125 32875102 . M6ACROT05999 REG00007 M6ATAR01838 Histone modification / Methylation EPIREG00037 EPITAR00205 EPITAR00560 . Histone modification Direct Enhancement m6A Histone modification directly impacts m6A modification through recruiting m6A regulator "Knockout (KO) of YTHDF2, an m6A reader, markedly enhanced demethylation of Histone H3 lysine 27 trimethylation (H3K27me3) on the promoters of proinflammatory cytokines (e.g., IL-6 and Interleukin-12 subunit beta (IL12B)). Furthermore, we identified H3K27me3 as a barrier for m6A modification during transcription. KDM6B recruits the m6A methyltransferase complex (METTL3/METTL14/WTAP) to facilitate the methylation of m6A in transcribing mRNA by removing adjacent H3K27me3 barriers. These results revealed cross-talk between m6A and H3K27me3 during bacterial infection, which has broader implications for deciphering epitranscriptomics in immune homeostasis." M6ADIS0125 32875102 . M6ACROT06000 REG00006 M6ATAR01838 Histone modification / Methylation EPIREG00037 EPITAR00205 EPITAR00560 . Histone modification Direct Enhancement m6A Histone modification directly impacts m6A modification through recruiting m6A regulator "Knockout (KO) of YTHDF2, an m6A reader, markedly enhanced demethylation of Histone H3 lysine 27 trimethylation (H3K27me3) on the promoters of proinflammatory cytokines (e.g., IL-6 and Interleukin-12 subunit beta (IL12B)). Furthermore, we identified H3K27me3 as a barrier for m6A modification during transcription. KDM6B recruits the m6A methyltransferase complex (METTL3/METTL14/WTAP) to facilitate the methylation of m6A in transcribing mRNA by removing adjacent H3K27me3 barriers. These results revealed cross-talk between m6A and H3K27me3 during bacterial infection, which has broader implications for deciphering epitranscriptomics in immune homeostasis." M6ADIS0125 32875102 . M6ACROT06001 REG00001 M6ATAR01460 Histone modification / Methylation EPIREG00060 EPITAR00201 EPITAR00561 Down regulation m6A Direct Inhibition Histone modification m6A modification impacts directly histone modification through modulating the expression level of histone-associated enzymes "FTO deletion and METTL16 overexpression significantly increased m6A levels. This led to the downregulation of the methyltransferase Histone-lysine N-methyltransferase SUV39H1 (SUV39H1), resulting in reduced Histone H3 lysine 9 trimethylation (H3K9me3) expression, which activated LTR7 and LTR12, subsequently activating ERV1." M6ADIS0094 39410722 . M6ACROT06002 REG00017 M6ATAR01460 Histone modification / Methylation EPIREG00060 EPITAR00201 EPITAR00561 Up regulation m6A Direct Enhancement Histone modification m6A modification impacts directly histone modification through modulating the expression level of histone-associated enzymes "FTO deletion and METTL16 overexpression significantly increased m6A levels. This led to the downregulation of the methyltransferase Histone-lysine N-methyltransferase SUV39H1 (SUV39H1), resulting in reduced Histone H3 lysine 9 trimethylation (H3K9me3) expression, which activated LTR7 and LTR12, subsequently activating ERV1." M6ADIS0094 39410722 . M6ACROT06019 REG00005 M6ATAR01621 Histone modification / Acetylation EPIREG00034 EPITAR00203 EPITAR00478 Down regulation Histone modification Indirect Enhancement m6A Histone modification indirectly regulates m6A modification through downstream signaling pathways Histone acetylation causes HSPA4 upregulation in GC tumor tissues. HSPA4 upregulation increases the protein stability of m6A demethylase ALKBH5. ALKBH5 decreases Lymphocyte function-associated antigen 3 (CD58) in GC cells through m6A methylation regulation. EP300/CREBBP-mediated Histone H3 lysine 27 acetylation (H3K27ac) modification plays an important role in HSPA4 overexpression in GC tissues. M6ADIS0057 38589927 . M6ACROT06020 REG00005 M6ATAR00140 Histone modification / Acetylation EPIREG00034 EPITAR00203 EPITAR00478 Up regulation Histone modification Indirect Enhancement m6A Histone modification indirectly regulates m6A modification through downstream signaling pathways Histone acetylation causes HSPA4 upregulation in GC tumor tissues. HSPA4 upregulation increases the protein stability of m6A demethylase ALKBH5. ALKBH5 decreases CD58 in GC cells through m6A methylation regulation. EP300/CREBBP-mediated Histone H3 lysine 27 acetylation (H3K27ac) modification plays an important role in HSPA4 overexpression in GC tissues. ALKBH5 promotes Gastric cancer invasion and metastasis by demethylating the lncRNA Nuclear paraspeckle assembly transcript 1 (NEAT1). M6ADIS0057 38589927; 31290116 . M6ACROT06021 REG00005 M6ATAR00732 Histone modification / Acetylation EPIREG00034 EPITAR00203 EPITAR00478 Down regulation Histone modification Indirect Enhancement m6A Histone modification indirectly regulates m6A modification through downstream signaling pathways "Histone acetylation causes HSPA4 upregulation in GC tumor tissues. HSPA4 upregulation increases the protein stability of m6A demethylase ALKBH5. ALKBH5 decreases CD58 in GC cells through m6A methylation regulation. EP300/CREBBP-mediated Histone H3 lysine 27 acetylation (H3K27ac) modification plays an important role in HSPA4 overexpression in GC tissues.Myt1 kinase (PKMYT1), as a downstream target of ALKBH5, promoted invasion and migration in GC. Moreover IGF2BP3 helped stabilize the mRNA stability of PKMYT1 via its m6A modification site." M6ADIS0057 38589927; 35114989 . M6ACROT06022 REG00005 M6ATAR00635 Histone modification / Acetylation EPIREG00034 EPITAR00203 EPITAR00478 Down regulation Histone modification Indirect Enhancement m6A Histone modification indirectly regulates m6A modification through downstream signaling pathways "Histone acetylation causes HSPA4 upregulation in GC tumor tissues. HSPA4 upregulation increases the protein stability of m6A demethylase ALKBH5. ALKBH5 decreases CD58 in GC cells through m6A methylation regulation. EP300/CREBBP-mediated Histone H3 lysine 27 acetylation (H3K27ac) modification plays an important role in HSPA4 overexpression in GC tissues. Transcriptional repressor protein YY1 (YY1) was regulated by ALKBH5 and YTHDF1-mediated m6A modification and served as an autophagy-dependent tumor driver to accelerate cancer progression through ATG4B transactivation, providing an exploitable therapeutic target for GC." M6ADIS0057 38589927; 37724907 . M6ACROT06023 REG00005 M6ATAR00997 Histone modification / Acetylation EPIREG00034 EPITAR00203 EPITAR00478 Down regulation Histone modification Indirect Enhancement m6A Histone modification indirectly regulates m6A modification through downstream signaling pathways Histone acetylation causes HSPA4 upregulation in GC tumor tissues. HSPA4 upregulation increases the protein stability of m6A demethylase ALKBH5. ALKBH5 decreases CD58 in GC cells through m6A methylation regulation. EP300/CREBBP-mediated Histone H3 lysine 27 acetylation (H3K27ac) modification plays an important role in HSPA4 overexpression in GC tissues. ALKBH5-mediated Glutathione-specific gamma-glutamylcyclotransferase 1 (CHAC1) depletion promotes malignant progression and decreases cisplatin-induced oxidative stress in gastric cancer M6ADIS0057 38589927; 38007439 M6ADRUG0047 M6ACROT06041 REG00013 M6ATAR01536 Histone modification / Lactylation EPIREG00035 EPITAR00208 EPITAR00028 Up regulation Histone modification Direct Enhancement m6A Histone modification directly impacts m6A modification through modulating the level of m6A regulator "CTCF interacts with HNRNPU through a FLG-AS1-dependent mechanism, facilitating the recruitment of p300 and activation of the m6A reader IGF2BP2 by Histone H3 lysine 18 lactylation (H3K18la). This activation promotes histone lactylation at the promoter region of IGF2BP2 stimulating the proliferation of PDAC cells. IGF2BP2 enhanced the mRNA stability of Macrophage colony-stimulating factor 1 (CSF1) and MYC." M6ADIS0061 39616247 M6ADRUG0024 M6ACROT06042 REG00013 M6ATAR00341 Histone modification / Lactylation EPIREG00035 EPITAR00208 EPITAR00028 Up regulation Histone modification Direct Enhancement m6A Histone modification directly impacts m6A modification through modulating the level of m6A regulator "CTCF interacts with HNRNPU through a FLG-AS1-dependent mechanism, facilitating the recruitment of p300 and activation of the m6A reader IGF2BP2 by Histone H3 lysine 18 lactylation (H3K18la). This activation promotes histone lactylation at the promoter region of IGF2BP2 stimulating the proliferation of PDAC cells. IGF2BP2 enhanced the mRNA stability of CSF1 and Myc proto-oncogene protein (MYC)." M6ADIS0061 39616247 M6ADRUG0024 M6ACROT06043 REG00005 M6ATAR01486 Histone modification / Acetylation EPIREG00067 EPITAR00203 EPITAR00183 Down regulation Histone modification Direct Inhibition m6A Histone modification directly impacts m6A modification through modulating the level of m6A regulator "HDACi reduces Ferroptosis suppressor protein 1 (AIFM2) by promoting its mRNA degradation. Specifically, it is confirmed that HDACi specifically targets HDAC1 and promotes the Histone H3 lysine 27 acetylation (H3K27ac) modification of fat mass- and obesity-associated gene (FTO) and AlkB Homolog 5, RNA Demethylase (ALKBH5), which results in significant activation of FTO and ALKBH5. The activation of FTO and ALKBH5 reduces N6-methyladenosine (m6A) modification on FSP1 mRNA, leading to its degradation in an IGF2BP1-dependent manner. Crucially, lactylation of HDAC1 K412 is essential for ferroptosis regulation. Both Vorinostat (SAHA) and Trichostatin A (TSA) notably diminish HDAC1 K412 lactylation in comparison to other HDAC1 inhibitors, exhibiting a consistent trend of increasing susceptibility to ferroptosis. " M6ADIS0059 39888307 M6ADRUG0258 M6ACROT06044 REG00012 M6ATAR01486 Histone modification / Acetylation EPIREG00067 EPITAR00203 EPITAR00179 Up regulation Histone modification Indirect Enhancement m6A Histone modification indirectly regulates m6A modification through downstream signaling pathways "HDACi reduces Ferroptosis suppressor protein 1 (AIFM2) by promoting its mRNA degradation. Specifically, it is confirmed that HDACi specifically targets HDAC1 and promotes the Histone H3 lysine 27 acetylation (H3K27ac) modification of fat mass- and obesity-associated gene (FTO) and AlkB Homolog 5, RNA Demethylase (ALKBH5), which results in significant activation of FTO and ALKBH5. The activation of FTO and ALKBH5 reduces N6-methyladenosine (m6A) modification on FSP1 mRNA, leading to its degradation in an IGF2BP1-dependent manner. Crucially, lactylation of HDAC1 K412 is essential for ferroptosis regulation. Both Vorinostat (SAHA) and Trichostatin A (TSA) notably diminish HDAC1 K412 lactylation in comparison to other HDAC1 inhibitors, exhibiting a consistent trend of increasing susceptibility to ferroptosis. " M6ADIS0059 39888307 M6ADRUG0258 M6ACROT06045 REG00012 M6ATAR01486 Histone modification / Acetylation EPIREG00067 EPITAR00203 EPITAR00183 Up regulation Histone modification Indirect Enhancement m6A Histone modification indirectly regulates m6A modification through downstream signaling pathways "HDACi reduces Ferroptosis suppressor protein 1 (AIFM2) by promoting its mRNA degradation. Specifically, it is confirmed that HDACi specifically targets HDAC1 and promotes the Histone H3 lysine 27 acetylation (H3K27ac) modification of fat mass- and obesity-associated gene (FTO) and AlkB Homolog 5, RNA Demethylase (ALKBH5), which results in significant activation of FTO and ALKBH5. The activation of FTO and ALKBH5 reduces N6-methyladenosine (m6A) modification on FSP1 mRNA, leading to its degradation in an IGF2BP1-dependent manner. Crucially, lactylation of HDAC1 K412 is essential for ferroptosis regulation. Both Vorinostat (SAHA) and Trichostatin A (TSA) notably diminish HDAC1 K412 lactylation in comparison to other HDAC1 inhibitors, exhibiting a consistent trend of increasing susceptibility to ferroptosis. " M6ADIS0059 39888307 M6ADRUG0258