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
M6ACROT02001	REG00024	M6ATAR01418	DNA methylation	EPIREG00027	EPITAR00175	.	Up regulation	DNA methylation	Indirect	Enhancement	m6A	DNA methylation indirectly regulates m6A modification through downstream signaling pathways	"In this study, we demonstrate that 5mC-mediated Suppressor of cytokine signaling 3 (SOCS3) suppression by DNMT3A leads to STAT3 activation. STAT3 transactivates HIF-1alpha, and HIF-1alpha subsequentially transactivates YTHDF1. YTHDF1 upregulates Collagen alpha-1 (COL1A1), COL1A2, COL3A1, COL5A2, and COL6A2, thus linking the 5mC-mediated initiation stage and the m6A-dependent perpetuation stage of the HSC activation cascade."	M6ADIS0017	36841889	.
M6ACROT02002	REG00024	M6ATAR01559	DNA methylation	EPIREG00027	EPITAR00175	.	Up regulation	DNA methylation	Indirect	Enhancement	m6A	DNA methylation indirectly regulates m6A modification through downstream signaling pathways	"In this study, we demonstrate that 5mC-mediated Suppressor of cytokine signaling 3 (SOCS3) suppression by DNMT3A leads to STAT3 activation. STAT3 transactivates HIF-1alpha, and HIF-1alpha subsequentially transactivates YTHDF1. YTHDF1 upregulates COL1A1, Collagen alpha-2(I) chain (COL1A2), COL3A1, COL5A2, and COL6A2, thus linking the 5mC-mediated initiation stage and the m6A-dependent perpetuation stage of the HSC activation cascade."	M6ADIS0017	36841889	.
M6ACROT02003	REG00024	M6ATAR00597	DNA methylation	EPIREG00027	EPITAR00175	.	Up regulation	DNA methylation	Indirect	Enhancement	m6A	DNA methylation indirectly regulates m6A modification through downstream signaling pathways	"In this study, we demonstrate that 5mC-mediated Suppressor of cytokine signaling 3 (SOCS3) suppression by DNMT3A leads to STAT3 activation. STAT3 transactivates HIF-1alpha, and HIF-1alpha subsequentially transactivates YTHDF1. YTHDF1 upregulates COL1A1, COL1A2, Collagen alpha-1 (III) chain (COL3A1), COL5A2, and COL6A2, thus linking the 5mC-mediated initiation stage and the m6A-dependent perpetuation stage of the HSC activation cascade."	M6ADIS0017	36841889	.
M6ACROT02004	REG00024	M6ATAR01560	DNA methylation	EPIREG00027	EPITAR00175	.	Up regulation	DNA methylation	Indirect	Enhancement	m6A	DNA methylation indirectly regulates m6A modification through downstream signaling pathways	"In this study, we demonstrate that 5mC-mediated Suppressor of cytokine signaling 3 (SOCS3) suppression by DNMT3A leads to STAT3 activation. STAT3 transactivates HIF-1alpha, and HIF-1alpha subsequentially transactivates YTHDF1. YTHDF1 upregulates COL1A1, COL1A2, COL3A1, Collagen alpha-2(V) chain (COL5A2), and COL6A2, thus linking the 5mC-mediated initiation stage and the m6A-dependent perpetuation stage of the HSC activation cascade."	M6ADIS0017	36841889	.
M6ACROT02005	REG00024	M6ATAR01561	DNA methylation	EPIREG00027	EPITAR00175	.	Up regulation	DNA methylation	Indirect	Enhancement	m6A	DNA methylation indirectly regulates m6A modification through downstream signaling pathways	"In this study, we demonstrate that 5mC-mediated Suppressor of cytokine signaling 3 (SOCS3) suppression by DNMT3A leads to STAT3 activation. STAT3 transactivates HIF-1alpha, and HIF-1alpha subsequentially transactivates YTHDF1. YTHDF1 upregulates COL1A1, COL1A2, COL3A1, COL5A2, and Collagen alpha-2(VI) chain (COL6A2), thus linking the 5mC-mediated initiation stage and the m6A-dependent perpetuation stage of the HSC activation cascade."	M6ADIS0017	36841889	.
M6ACROT02006	REG00023	M6ATAR01562	DNA methylation	EPIREG00020	EPITAR00176	.	.	m6A	Direct	Enhancement	DNA methylation	m6A modification directly impacts DNA methylation through recruiting DNA methyltransferases or demethylases. 	"RNA N6-methyladenosine (m6A) reader, YTHDC2, occupies genomic loci of the primate-specific TE, Long Terminal Repeat 7 (LTR7)/ANKRD13C divergent transcript (ANKRD13C-DT), specifically through its interaction with m6A-modified HERV-H RNAs. Unexpectedly, YTHDC2 recruits the DNA 5-methylcytosine (5mC)-demethylase, TET1, to remove 5mC from LTR7/HERV-H and prevent epigenetic silencing. Functionally, the YTHDC2/LTR7 axis inhibits neural differentiation of hESCs."	.	37474847	.
M6ACROT02007	REG00007	M6ATAR01562	DNA methylation	EPIREG00020	EPITAR00176	.	.	m6A	Indirect	Enhancement	DNA methylation	m6A modification indirectly regulates DNA methylation through downstream signaling pathways	"After ANKRD13C divergent transcript (ANKRD13C-DT) is methylated by METTL3, RNA N6-methyladenosine (m6A) reader, YTHDC2, occupies genomic loci of the primate-specific TE, Long Terminal Repeat 7 (LTR7)/HERV-H, specifically through its interaction with m6A-modified HERV-H RNAs. Unexpectedly, YTHDC2 recruits the DNA 5-methylcytosine (5mC)-demethylase, TET1, to remove 5mC from LTR7/HERV-H and prevent epigenetic silencing. Functionally, the YTHDC2/LTR7 axis inhibits neural differentiation of hESCs."	.	37474847	.
M6ACROT02008	REG00007	M6ATAR01842	DNA methylation	EPIREG00020	EPITAR00531	.	.	m6A	Indirect	Enhancement	DNA methylation	m6A modification indirectly regulates DNA methylation through downstream signaling pathways	"Here, we show that METTL3-mediated RNA N6-methyladenosine (m6A) formation leads to DNA demethylation in nearby genomic loci in normal and cancer cells, which is mediated by the interaction between m6A reader FXR1 and DNA 5-methylcytosine dioxygenase TET1. Upon recognizing RNA m6A, FXR1 recruits TET1 to genomic loci to demethylate DNA, leading to reprogrammed chromatin accessibility and gene transcription. These gene include DNA-binding protein SATB2 (SATB2), RPIA, WNT7B, BCL6, FAT4 and SAMD9L."	M6ADIS0056	36071173	.
M6ACROT02009	REG00051	M6ATAR01842	DNA methylation	EPIREG00020	EPITAR00531	.	.	m6A	Direct	Enhancement	DNA methylation	m6A modification directly impacts DNA methylation through recruiting DNA methyltransferases or demethylases. 	"Here, we show that METTL3-mediated RNA N6-methyladenosine (m6A) formation leads to DNA demethylation in nearby genomic loci in normal and cancer cells, which is mediated by the interaction between m6A reader FXR1 and DNA 5-methylcytosine dioxygenase TET1. Upon recognizing RNA m6A, FXR1 recruits TET1 to genomic loci to demethylate DNA, leading to reprogrammed chromatin accessibility and gene transcription. These gene include DNA-binding protein SATB2 (SATB2), RPIA, WNT7B, BCL6, FAT4 and SAMD9L."	M6ADIS0056	36071173	.
M6ACROT02010	REG00007	M6ATAR00637	DNA methylation	EPIREG00020	EPITAR00027	.	Down regulation	m6A	Direct	Inhibition	DNA methylation	m6A modification directly impacts DNA methylation through modulating the expression level of DNA methyltransferases or demethylases. 	"Our study revealed that METTL3 targeted Methylcytosine dioxygenase TET1 (TET1) mRNA via m6A methylation, and TET1, in turn, mediated DNA methylation targeting METTL3 to affect mRNA m6A methylation, thus forming a negative feedback loop that regulated myoblast differentiation. "	.	36375665	.
M6ACROT02011	REG00008	M6ATAR00637	DNA methylation	EPIREG00020	EPITAR00027	.	Down regulation	m6A	Direct	Inhibition	DNA methylation	m6A modification directly impacts DNA methylation through modulating the expression level of DNA methyltransferases or demethylases. 	"Our study revealed that Methyltransferase-like protein 3 (METTL3) targeted Methylcytosine dioxygenase TET1 (TET1) mRNA via m6A methylation in a YTHDF2 dependent manner, and TET1, in turn, mediated DNA methylation targeting METTL3 to affect mRNA m6A methylation, thus forming a negative feedback loop that regulated myoblast differentiation. "	.	36375665	.
M6ACROT02012	REG00007	M6ATAR00637	DNA methylation	EPIREG00020	EPITAR00027	.	Down regulation	DNA methylation	Direct	Enhancement	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"Our study revealed that METTL3 targeted Methylcytosine dioxygenase TET1 (TET1) mRNA via m6A methylation, and TET1, in turn, mediated DNA methylation targeting METTL3 to affect mRNA m6A methylation, thus forming a negative feedback loop that regulated myoblast differentiation. "	.	36375665	.
M6ACROT02013	REG00022	M6ATAR00096	DNA methylation	.	EPITAR00177	.	Down regulation	m6A	Indirect	Inhibition	DNA methylation	m6A modification indirectly regulates DNA methylation through downstream signaling pathways	"FOXF1 adjacent non-coding developmental regulatory RNA (FENDRR) overexpression inhibited hypoxia-induced HPAEC pyroptosis. Additionally, Dynamin-1-like protein (DRP1) is a downstream target gene of FENDRR, and FENDRR formed an RNA-DNA triplex with the promoter of DRP1, which led to an increase in DRP1 promoter methylation that decreased the transcriptional level of DRP1. Notably, we illustrated that the m6A reader YTHDC1 plays an important role in m6A-modified FENDRR degradation."	M6ADIS0032	36284300	.
M6ACROT02014	REG00007	M6ATAR01564	DNA methylation	EPIREG00028	EPITAR00178	.	.	m6A	Indirect	Inhibition	DNA methylation	m6A modification indirectly regulates DNA methylation through downstream signaling pathways	"Moreover, our findings first emphasized the functional importance of IGF2BPs (IGF2BP2 and IGF2BP3) as epigenetic R-loop readers in transcriptional genetic regulation and cancer biology. In addition, our research provides a novel RBM15/IGF2BPs/DNMT1 trans-omics regulation m6A axis targeting Semaphorin-3F (SEMA3F) in a METTL3 dependent manner, indicating the new crosstalk between RNA m6A methylation and DNA methylation in prostate cancer."	M6ADIS0068	38658974	M6ADRUG0194
M6ACROT02015	REG00020	M6ATAR01564	DNA methylation	EPIREG00028	EPITAR00178	.	.	m6A	Indirect	Inhibition	DNA methylation	m6A modification indirectly regulates DNA methylation through downstream signaling pathways	"Moreover, our findings first emphasized the functional importance of IGF2BPs (IGF2BP2 and IGF2BP3) as epigenetic R-loop readers in transcriptional genetic regulation and cancer biology. In addition, our research provides a novel RBM15/IGF2BPs/DNMT1 trans-omics regulation m6A axis targeting Semaphorin-3F (SEMA3F), indicating the new crosstalk between RNA m6A methylation and DNA methylation in prostate cancer."	M6ADIS0068	38658974	M6ADRUG0194
M6ACROT02016	REG00013	M6ATAR01564	DNA methylation	EPIREG00028	EPITAR00178	.	.	m6A	Direct	Inhibition	DNA methylation	m6A modification directly impacts DNA methylation through recruiting DNA methyltransferases or demethylases. 	"Moreover, our findings first emphasized the functional importance of IGF2BPs (IGF2BP2 and IGF2BP3) as epigenetic R-loop readers in transcriptional genetic regulation and cancer biology. In addition, our research provides a novel RBM15/IGF2BPs/DNMT1 trans-omics regulation m6A axis targeting Semaphorin-3F (SEMA3F), indicating the new crosstalk between RNA m6A methylation and DNA methylation in prostate cancer."	M6ADIS0068	38658974	M6ADRUG0194
M6ACROT02017	REG00014	M6ATAR01564	DNA methylation	EPIREG00028	EPITAR00178	.	.	m6A	Direct	Inhibition	DNA methylation	m6A modification directly impacts DNA methylation through recruiting DNA methyltransferases or demethylases. 	"Moreover, our findings first emphasized the functional importance of IGF2BPs (IGF2BP2 and IGF2BP3) as epigenetic R-loop readers in transcriptional genetic regulation and cancer biology. In addition, our research provides a novel RBM15/IGF2BPs/DNMT1 trans-omics regulation m6A axis targeting Semaphorin-3F (SEMA3F), indicating the new crosstalk between RNA m6A methylation and DNA methylation in prostate cancer."	M6ADIS0068	38658974	M6ADRUG0194
M6ACROT02018	REG00008	M6ATAR01564	DNA methylation	EPIREG00028	EPITAR00178	.	.	m6A	Direct	Enhancement	DNA methylation	m6A modification directly impacts DNA methylation through recruiting DNA methyltransferases or demethylases. 	"Moreover, our findings first emphasized the functional importance of IGF2BPs (IGF2BP2 and IGF2BP3) as epigenetic R-loop readers in transcriptional genetic regulation and cancer biology. In addition, our research provides a novel RBM15/IGF2BPs/DNMT1 trans-omics regulation m6A axis targeting Semaphorin-3F (SEMA3F), indicating the new crosstalk between RNA m6A methylation and DNA methylation in prostate cancer. Notably, IGF2BPs overexpression also affected the colocalization of YTHDF2 with R-loops in the nucleus"	M6ADIS0068	38658974	M6ADRUG0194
M6ACROT02019	REG00001	M6ATAR00475	DNA methylation	EPIREG00028	EPITAR00179	.	Up regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"Inhibition of DNA methyltransferases (DNMT1, DNMT3A, and DNMT3B) by 5-azacytidine (5-aza) reversed alcohol-induced kidney injury and decreased the mRNA and protein levels of FTO. Importantly, we found that FTO, the m6A demethylase, epigenetically modified Peroxisome proliferator-activated receptor alpha (PPARalpha/PPARA) in a YTH domain family 2 (YTHDF2)-dependent manner, which resulted in inflammation in alcoholic kidney injury models. In conclusion, our findings indicate that alcohol increases the methylation of PPAR-alpha m6A by FTO-mediated YTHDF2 epigenetic modification, which ultimately leads to the activation of NLRP3 inflammasomes and NF-kappaB-driven renal inflammation in the kidney. "	M6ADIS0025	33157234	M6ADRUG0184
M6ACROT02020	REG00001	M6ATAR00475	DNA methylation	EPIREG00027	EPITAR00179	.	Up regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"Inhibition of DNA methyltransferases (DNMT1, DNMT3A, and DNMT3B) by 5-azacytidine (5-aza) reversed alcohol-induced kidney injury and decreased the mRNA and protein levels of FTO. Importantly, we found that FTO, the m6A demethylase, epigenetically modified Peroxisome proliferator-activated receptor alpha (PPARalpha/PPARA) in a YTH domain family 2 (YTHDF2)-dependent manner, which resulted in inflammation in alcoholic kidney injury models. In conclusion, our findings indicate that alcohol increases the methylation of PPAR-alpha m6A by FTO-mediated YTHDF2 epigenetic modification, which ultimately leads to the activation of NLRP3 inflammasomes and NF-kappaB-driven renal inflammation in the kidney. "	M6ADIS0025	33157234	M6ADRUG0184
M6ACROT02021	REG00001	M6ATAR00475	DNA methylation	EPIREG00029	EPITAR00179	.	Up regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"Inhibition of DNA methyltransferases (DNMT1, DNMT3A, and DNMT3B) by 5-azacytidine (5-aza) reversed alcohol-induced kidney injury and decreased the mRNA and protein levels of FTO. Importantly, we found that FTO, the m6A demethylase, epigenetically modified Peroxisome proliferator-activated receptor alpha (PPARalpha/PPARA) in a YTH domain family 2 (YTHDF2)-dependent manner, which resulted in inflammation in alcoholic kidney injury models. In conclusion, our findings indicate that alcohol increases the methylation of PPAR-alpha m6A by FTO-mediated YTHDF2 epigenetic modification, which ultimately leads to the activation of NLRP3 inflammasomes and NF-kappaB-driven renal inflammation in the kidney. "	M6ADIS0025	33157234	M6ADRUG0184
M6ACROT02022	REG00008	M6ATAR00475	DNA methylation	EPIREG00028	EPITAR00179	.	Down regulation	DNA methylation	Indirect	Enhancement	m6A	DNA methylation indirectly regulates m6A modification through downstream signaling pathways	"Inhibition of DNA methyltransferases (DNMT1, DNMT3A, and DNMT3B) by 5-azacytidine (5-aza) reversed alcohol-induced kidney injury and decreased the mRNA and protein levels of FTO alpha-ketoglutarate dependent dioxygenase (FTO). Importantly, we found that FTO, the m6A demethylase, epigenetically modified Peroxisome proliferator-activated receptor alpha (PPARalpha/PPARA) in a YTH domain family 2 (YTHDF2)-dependent manner, which resulted in inflammation in alcoholic kidney injury models. In conclusion, our findings indicate that alcohol increases the methylation of PPAR-alpha m6A by FTO-mediated YTHDF2 epigenetic modification, which ultimately leads to the activation of NLRP3 inflammasomes and NF-kappaB-driven renal inflammation in the kidney. "	M6ADIS0025	33157234	M6ADRUG0184
M6ACROT02023	REG00008	M6ATAR00475	DNA methylation	EPIREG00027	EPITAR00179	.	Down regulation	DNA methylation	Indirect	Enhancement	m6A	DNA methylation indirectly regulates m6A modification through downstream signaling pathways	"Inhibition of DNA methyltransferases (DNMT1, DNMT3A, and DNMT3B) by 5-azacytidine (5-aza) reversed alcohol-induced kidney injury and decreased the mRNA and protein levels of FTO alpha-ketoglutarate dependent dioxygenase (FTO). Importantly, we found that FTO, the m6A demethylase, epigenetically modified Peroxisome proliferator-activated receptor alpha (PPARalpha/PPARA) in a YTH domain family 2 (YTHDF2)-dependent manner, which resulted in inflammation in alcoholic kidney injury models. In conclusion, our findings indicate that alcohol increases the methylation of PPAR-alpha m6A by FTO-mediated YTHDF2 epigenetic modification, which ultimately leads to the activation of NLRP3 inflammasomes and NF-kappaB-driven renal inflammation in the kidney. "	M6ADIS0025	33157234	M6ADRUG0184
M6ACROT02024	REG00008	M6ATAR00475	DNA methylation	EPIREG00029	EPITAR00179	.	Down regulation	DNA methylation	Indirect	Enhancement	m6A	DNA methylation indirectly regulates m6A modification through downstream signaling pathways	"Inhibition of DNA methyltransferases (DNMT1, DNMT3A, and DNMT3B) by 5-azacytidine (5-aza) reversed alcohol-induced kidney injury and decreased the mRNA and protein levels of FTO alpha-ketoglutarate dependent dioxygenase (FTO). Importantly, we found that FTO, the m6A demethylase, epigenetically modified Peroxisome proliferator-activated receptor alpha (PPARalpha/PPARA) in a YTH domain family 2 (YTHDF2)-dependent manner, which resulted in inflammation in alcoholic kidney injury models. In conclusion, our findings indicate that alcohol increases the methylation of PPAR-alpha m6A by FTO-mediated YTHDF2 epigenetic modification, which ultimately leads to the activation of NLRP3 inflammasomes and NF-kappaB-driven renal inflammation in the kidney. "	M6ADIS0025	33157234	M6ADRUG0184
M6ACROT02025	REG00005	M6ATAR00658	DNA methylation	EPIREG00029	EPITAR00180	.	Up regulation	m6A	Direct	Enhancement	DNA methylation	m6A modification directly impacts DNA methylation through modulating the expression level of DNA methyltransferases or demethylases. 	"ALKBH5 deficiency-induced m6A hypomethylation of DNA (cytosine-5)-methyltransferase 3B (DNMT3B) leads to less recognition of YTHDF2, resulting in enhanced stability of DNMT3B mRNA. Increased expression of DNMT3B modulated the Transcription factor E4F1 (E4F1) level upon DNA methylation patterns causing cellular arrest and senescent phenotype."	M6ADIS0168	35340126	.
M6ACROT02026	REG00008	M6ATAR00658	DNA methylation	EPIREG00029	EPITAR00180	.	Down regulation	m6A	Direct	Inhibition	DNA methylation	m6A modification directly impacts DNA methylation through modulating the expression level of DNA methyltransferases or demethylases. 	"ALKBH5 deficiency-induced m6A hypomethylation of DNA (cytosine-5)-methyltransferase 3B (DNMT3B) leads to less recognition of YTHDF2, resulting in enhanced stability of DNMT3B mRNA. Increased expression of DNMT3B modulated the Transcription factor E4F1 (E4F1) level upon DNA methylation patterns causing cellular arrest and senescent phenotype."	M6ADIS0168	35340126	.
M6ACROT02027	REG00023	M6ATAR00053	DNA methylation	EPIREG00022	EPITAR00181	.	Up regulation	m6A	Indirect	Inhibition	DNA methylation	m6A modification indirectly regulates DNA methylation through downstream signaling pathways	"The mechanism analysis revealed that YTHDC2-mediated m6A modification stabilized Circ_YTHDC2. In addition, circYTHDC2 negatively regulated the expression of Ten-Eleven Translocation 2 (TET2) by targeting the unstable motif of TET2 3'UTR, thereby promoting the proliferation and migration of VSMCs, and TET2 functions as an upstream regulator of Myocardin (MYOCD), SRF and KLF4, which are key drivers of phenotypic plasticity of VSMC. These findings suggest that the YTHDC2/circYTHDC2/TET2 pathway is an important target of metformin in preventing the progression of VSMCs dysfunction."	M6ADIS0077	34660707	M6ADRUG0007
M6ACROT02028	REG00023	M6ATAR00053	DNA methylation	EPIREG00022	EPITAR00182	.	Up regulation	m6A	Indirect	Inhibition	DNA methylation	m6A modification indirectly regulates DNA methylation through downstream signaling pathways	"The mechanism analysis revealed that YTHDC2-mediated m6A modification stabilized Circ_YTHDC2. In addition, circYTHDC2 negatively regulated the expression of Ten-Eleven Translocation 2 (TET2) by targeting the unstable motif of TET2 3'UTR, thereby promoting the proliferation and migration of VSMCs, and TET2 functions as an upstream regulator of MYOCD, Serum response factor (SRF) and KLF4, which are key drivers of phenotypic plasticity of VSMC. These findings suggest that the YTHDC2/circYTHDC2/TET2 pathway is an important target of metformin in preventing the progression of VSMCs dysfunction."	M6ADIS0077	34660707	M6ADRUG0007
M6ACROT02029	REG00023	M6ATAR00053	DNA methylation	EPIREG00022	EPITAR00173	.	Up regulation	m6A	Indirect	Inhibition	DNA methylation	m6A modification indirectly regulates DNA methylation through downstream signaling pathways	"The mechanism analysis revealed that YTHDC2-mediated m6A modification stabilized Circ_YTHDC2. In addition, circYTHDC2 negatively regulated the expression of Ten-Eleven Translocation 2 (TET2) by targeting the unstable motif of TET2 3'UTR, thereby promoting the proliferation and migration of VSMCs, and TET2 functions as an upstream regulator of MYOCD, SRF and Krueppel-like factor 4 (KLF4), which are key drivers of phenotypic plasticity of VSMC. These findings suggest that the YTHDC2/circYTHDC2/TET2 pathway is an important target of metformin in preventing the progression of VSMCs dysfunction."	M6ADIS0077	34660707	M6ADRUG0007
M6ACROT02030	REG00007	M6ATAR00127	DNA methylation	EPIREG00028	EPITAR00027	.	Up regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	Quantitative chromatin immunoprecipitation (ChIP) assays showed that CSC substantially reduced the bindings of DNA methyltransferase 1 (DNMT1) and DNMT3A to the METTL3 promoter. METTL3 increases m6A level of microRNA 25 (MIR25) and upregulates miR-25 in an NKAP-dependent manner.	M6ADIS0061	31015415	.
M6ACROT02031	REG00007	M6ATAR00127	DNA methylation	EPIREG00027	EPITAR00027	.	Up regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	Quantitative chromatin immunoprecipitation (ChIP) assays showed that CSC substantially reduced the bindings of DNA methyltransferase 1 (DNMT1) and DNMT3A to the METTL3 promoter. METTL3 increases m6A level of microRNA 25 (MIR25) and upregulates miR-25 in an NKAP-dependent manner.	M6ADIS0061	31015415	.
M6ACROT02032	REG00019	M6ATAR00127	DNA methylation	EPIREG00028	EPITAR00027	.	Up regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	Quantitative chromatin immunoprecipitation (ChIP) assays showed that CSC substantially reduced the bindings of DNA methyltransferase 1 (DNMT1) and DNMT3A to the Methyltransferase-like protein 3 (METTL3) promoter. METTL3 increases m6A level of microRNA 25 (MIR25) and upregulates miR-25 in an NKAP-dependent manner.	M6ADIS0061	31015415	.
M6ACROT02033	REG00019	M6ATAR00127	DNA methylation	EPIREG00027	EPITAR00027	.	Up regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	Quantitative chromatin immunoprecipitation (ChIP) assays showed that CSC substantially reduced the bindings of DNA methyltransferase 1 (DNMT1) and DNMT3A to the Methyltransferase-like protein 3 (METTL3) promoter. METTL3 increases m6A level of microRNA 25 (MIR25) and upregulates miR-25 in an NKAP-dependent manner.	M6ADIS0061	31015415	.
M6ACROT02034	REG00005	M6ATAR00404	DNA methylation	EPIREG00028	EPITAR00183	.	Up regulation	DNA methylation	Direct	Enhancement	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"Loss of LKB1 promotes ALKBH5 transcription by DNMT1-mediated DNA methylation mechanism, reduces m6A modification, and increases the stability of m6A target oncogenes, thus contributing to aggressive phenotypes of KRAS-mutated lung cancer. ALKBH5 demethylation of m6A stabilized oncogenic drivers, such as Transcription factor SOX-2 (SOX2), SMAD7, and MYC, through a pathway dependent on YTHDF2, an m6A reader protein."	M6ADIS0007	34016959	.
M6ACROT02035	REG00005	M6ATAR00397	DNA methylation	EPIREG00028	EPITAR00183	.	Up regulation	DNA methylation	Direct	Enhancement	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"Loss of LKB1 promotes ALKBH5 transcription by DNMT1-mediated DNA methylation mechanism, reduces m6A modification, and increases the stability of m6A target oncogenes, thus contributing to aggressive phenotypes of KRAS-mutated lung cancer. ALKBH5 demethylation of m6A stabilized oncogenic drivers, such as SOX2, Mothers against decapentaplegic homolog 7 (SMAD7), and MYC, through a pathway dependent on YTHDF2, an m6A reader protein."	M6ADIS0007	34016959	.
M6ACROT02036	REG00005	M6ATAR00341	DNA methylation	EPIREG00028	EPITAR00183	.	Up regulation	DNA methylation	Direct	Enhancement	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"Loss of LKB1 promotes ALKBH5 transcription by DNMT1-mediated DNA methylation mechanism, reduces m6A modification, and increases the stability of m6A target oncogenes, thus contributing to aggressive phenotypes of KRAS-mutated lung cancer. ALKBH5 demethylation of m6A stabilized oncogenic drivers, such as SOX2, SMAD7, and Myc proto-oncogene protein (MYC), through a pathway dependent on YTHDF2, an m6A reader protein."	M6ADIS0007	34016959	.
M6ACROT02037	REG00008	M6ATAR00404	DNA methylation	EPIREG00028	EPITAR00183	.	Down regulation	DNA methylation	Indirect	Inhibition	m6A	DNA methylation indirectly regulates m6A modification through downstream signaling pathways	"Loss of LKB1 promotes RNA demethylase ALKBH5 (ALKBH5) transcription by DNMT1-mediated DNA methylation mechanism, reduces m6A modification, and increases the stability of m6A target oncogenes, thus contributing to aggressive phenotypes of KRAS-mutated lung cancer. ALKBH5 demethylation of m6A stabilized oncogenic drivers, such as Transcription factor SOX-2 (SOX2), SMAD7, and MYC, through a pathway dependent on YTHDF2, an m6A reader protein."	M6ADIS0007	34016959	.
M6ACROT02038	REG00008	M6ATAR00397	DNA methylation	EPIREG00028	EPITAR00183	.	Down regulation	DNA methylation	Indirect	Inhibition	m6A	DNA methylation indirectly regulates m6A modification through downstream signaling pathways	"Loss of LKB1 promotes RNA demethylase ALKBH5 (ALKBH5) transcription by DNMT1-mediated DNA methylation mechanism, reduces m6A modification, and increases the stability of m6A target oncogenes, thus contributing to aggressive phenotypes of KRAS-mutated lung cancer. ALKBH5 demethylation of m6A stabilized oncogenic drivers, such as SOX2, Mothers against decapentaplegic homolog 7 (SMAD7), and MYC, through a pathway dependent on YTHDF2, an m6A reader protein."	M6ADIS0007	34016959	.
M6ACROT02039	REG00008	M6ATAR00341	DNA methylation	EPIREG00028	EPITAR00183	.	Down regulation	DNA methylation	Indirect	Inhibition	m6A	DNA methylation indirectly regulates m6A modification through downstream signaling pathways	"Loss of LKB1 promotes RNA demethylase ALKBH5 (ALKBH5) transcription by DNMT1-mediated DNA methylation mechanism, reduces m6A modification, and increases the stability of m6A target oncogenes, thus contributing to aggressive phenotypes of KRAS-mutated lung cancer. ALKBH5 demethylation of m6A stabilized oncogenic drivers, such as SOX2, SMAD7, and Myc proto-oncogene protein (MYC), through a pathway dependent on YTHDF2, an m6A reader protein."	M6ADIS0007	34016959	.
M6ACROT02040	REG00007	M6ATAR01568	DNA methylation	EPIREG00028	EPITAR00065	.	.	m6A	Direct	Inhibition	DNA methylation	m6A modification directly impacts DNA methylation through modulating the expression level of DNA methyltransferases or demethylases. 	"Insulin-like Growth Factor Binding Protein 7 Overlapping Transcript suppresses the occupancy of DNMT1 and DNMT3A on the Insulin-like growth factor-binding protein 7 (IGFBP7) promoter, thereby inhibiting methylation of the IGFBP7 promoter. The upregulation of IGFBP7-OT in OA is partially controlled by METTL3-mediated N-methyladenosine (mA) modification. Collectively, our findings reveal that mA modification of IGFBP7-OT promotes OA progression by regulating the DNMT1/DNMT3A-IGFBP7 axis and provide a potential therapeutical target for OA treatment."	M6ADIS0317	37270777	.
M6ACROT02041	REG00007	M6ATAR01568	DNA methylation	EPIREG00027	EPITAR00065	.	.	m6A	Direct	Inhibition	DNA methylation	m6A modification directly impacts DNA methylation through modulating the expression level of DNA methyltransferases or demethylases. 	"Insulin-like Growth Factor Binding Protein 7 Overlapping Transcript suppresses the occupancy of DNMT1 and DNMT3A on the Insulin-like growth factor-binding protein 7 (IGFBP7) promoter, thereby inhibiting methylation of the IGFBP7 promoter. The upregulation of IGFBP7-OT in OA is partially controlled by METTL3-mediated N-methyladenosine (mA) modification. Collectively, our findings reveal that mA modification of IGFBP7-OT promotes OA progression by regulating the DNMT1/DNMT3A-IGFBP7 axis and provide a potential therapeutical target for OA treatment."	M6ADIS0317	37270777	.
M6ACROT02042	REG00007	M6ATAR01703	DNA methylation	EPIREG00028	EPITAR00027	.	Down regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"In addition, this study revealed that the DNMT1/METTL3 pathway affected Ang II-induced apoptosis in NRCMs by upregulating Protein mono-ADP-ribosyltransferase PARP10 (PARP10). the role of the DNMT1/METTL3 pathway in cardiac hypertrophy and provided a novel molecular mechanism describing the physiological and pathological processes."	M6ADIS0100	38314261; 33020597	M6ADRUG0209
M6ACROT02043	REG00007	M6ATAR01569	DNA methylation	EPIREG00028	EPITAR00184	.	.	m6A	Direct	Enhancement	DNA methylation	m6A modification directly impacts DNA methylation through modulating the expression level of DNA methyltransferases or demethylases. 	"METTL3-mediated m6A methylation of DNA (cytosine-5)-methyltransferase 1 (DNMT1) up-regulates Forkhead box protein O3 (FOXO3) promoter methylation, thereby promoting the progression of NSCLC."	M6ADIS0007	38586389	.
M6ACROT02044	REG00007	M6ATAR00566	DNA methylation	EPIREG00028	EPITAR00524	.	Down regulation	m6A	Direct	Enhancement	DNA methylation	m6A modification directly impacts DNA methylation through recruiting DNA methyltransferases or demethylases.	"METTL3-METTL14 recruits the DNA methyltransferase DNMT1 to chromatin for gene-body methylation including Neurogenic locus notch homolog protein 2 (NOTCH2), Eomes, Insr and Smad3, whose expression is fine-tuned by both gene-body 5mC, which promotes transcription, and m6A, which destabilizes transcripts. We demonstrate that METTL3-METTL14-dependent 5mC and m6A are both essential for the differentiation of embryonic stem cells into embryoid bodies and that the upregulation of key differentiation genes during early differentiation depends on the dynamic balance between increased 5mC and decreased m6A."	.	39826545	.
M6ACROT02045	REG00006	M6ATAR00566	DNA methylation	EPIREG00028	EPITAR00524	.	Down regulation	m6A	Direct	Enhancement	DNA methylation	m6A modification directly impacts DNA methylation through recruiting DNA methyltransferases or demethylases.	"METTL3-METTL14 recruits the DNA methyltransferase DNMT1 to chromatin for gene-body methylation including Neurogenic locus notch homolog protein 2 (NOTCH2), Eomes, Insr and Smad3, whose expression is fine-tuned by both gene-body 5mC, which promotes transcription, and m6A, which destabilizes transcripts. We demonstrate that METTL3-METTL14-dependent 5mC and m6A are both essential for the differentiation of embryonic stem cells into embryoid bodies and that the upregulation of key differentiation genes during early differentiation depends on the dynamic balance between increased 5mC and decreased m6A."	.	39826545	.
M6ACROT02046	REG00009	M6ATAR01569	DNA methylation	EPIREG00028	.	.	.	m6A	Direct	Enhancement	DNA methylation	m6A modification directly impacts DNA methylation through modulating the expression level of DNA methyltransferases or demethylases. 	WTAP expression is elevated in HG-induced HUVECs and epigenetically regulates the m6A modification of DNA (cytosine-5)-methyltransferase 1 (DNMT1) to impair diabetic wound healing.	M6ADIS0257	40093271	.
M6ACROT02047	REG00007	M6ATAR00141	DNA methylation	EPIREG00027	EPITAR00185	.	Up regulation	m6A	Indirect	Enhancement	DNA methylation	m6A modification indirectly regulates DNA methylation through downstream signaling pathways	"METTL3 stabilized Metastasis associated lung adenocarcinoma transcript 1 (MALAT1) expression by promoting m6A modification of MALAT1. MALAT1 promoted Secreted frizzled-related protein 2 (SFRP2) methylation and led to reduced SFRP2 expression by recruiting DNMT1, DNMT3A, and DNMT3B to the promoter region of SFRP2. Furthermore, SFRP2 facilitated activation of the Wnt/beta-catenin signaling. By this mechanism, METTL3 suppressed autism-like symptoms and hippocampal neuron apoptosis."	.	36327957	M6ADRUG0210
M6ACROT02048	REG00007	M6ATAR00141	DNA methylation	EPIREG00029	EPITAR00185	.	Up regulation	m6A	Indirect	Enhancement	DNA methylation	m6A modification indirectly regulates DNA methylation through downstream signaling pathways	"METTL3 stabilized Metastasis associated lung adenocarcinoma transcript 1 (MALAT1) expression by promoting m6A modification of MALAT1. MALAT1 promoted Secreted frizzled-related protein 2 (SFRP2) methylation and led to reduced SFRP2 expression by recruiting DNMT1, DNMT3A, and DNMT3B to the promoter region of SFRP2. Furthermore, SFRP2 facilitated activation of the Wnt/beta-catenin signaling. By this mechanism, METTL3 suppressed autism-like symptoms and hippocampal neuron apoptosis."	.	36327957	M6ADRUG0210
M6ACROT02049	REG00007	M6ATAR00141	DNA methylation	EPIREG00028	EPITAR00185	.	Up regulation	m6A	Indirect	Enhancement	DNA methylation	m6A modification indirectly regulates DNA methylation through downstream signaling pathways	"METTL3 stabilized Metastasis associated lung adenocarcinoma transcript 1 (MALAT1) expression by promoting m6A modification of MALAT1. MALAT1 promoted Secreted frizzled-related protein 2 (SFRP2) methylation and led to reduced SFRP2 expression by recruiting DNMT1, DNMT3A, and DNMT3B to the promoter region of SFRP2. Furthermore, SFRP2 facilitated activation of the Wnt/beta-catenin signaling. By this mechanism, METTL3 suppressed autism-like symptoms and hippocampal neuron apoptosis."	.	36327957	M6ADRUG0210
M6ACROT02050	REG00017	M6ATAR00388	DNA methylation	EPIREG00028	EPITAR00186	.	Down regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	METTL16 was expressed at lower levels in PTC tissues because of DNMT1-mediated hypermethylation of its promoter. These results confirm the crucial role of METTL16 in restraining PTC progression through Stearoyl-CoA desaturase (SCD)-activated lipid metabolism in cooperation with YTHDC2. This suggests that the combination of METTL16 and anti-SCD1 blockade might constitute an effective therapy for PTC.	M6ADIS0312	38334797	M6ADRUG0210
M6ACROT02051	REG00023	M6ATAR00388	DNA methylation	EPIREG00028	EPITAR00186	.	Down regulation	DNA methylation	Indirect	Inhibition	m6A	DNA methylation indirectly regulates m6A modification through downstream signaling pathways	"Methyltransferase 16, RNA N6-adenosine (METTL16) was expressed at lower levels in PTC tissues because of DNMT1-mediated hypermethylation of its promoter. These results confirm the crucial role of METTL16 in restraining PTC progression through Stearoyl-CoA desaturase (SCD)-activated lipid metabolism in cooperation with YTHDC2. This suggests that the combination of METTL16 and anti-SCD1 blockade might constitute an effective therapy for PTC."	M6ADIS0312	38334797	M6ADRUG0210
M6ACROT02052	REG00001	M6ATAR00610	DNA methylation	EPIREG00028	EPITAR00179	.	Down regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"The comprehensive functional annotations indicated these genes might mediate a detailed immune or inflammatory response or signaling pathways in the OLF pathogenesis. Suppressor of cytokine signaling 3 (SOCS3) was identified as a core gene, which was associated with multiple immune infiltrates and 5mC/m6A modifiers in OLF, and the crosstalk between DNMT1 and FTO on affecting SOCS3 expression might play a significant role in OLF pathogenesis."	M6ADIS0113	35712246	.
M6ACROT02053	REG00029	M6ATAR01414	DNA methylation	EPIREG00028	EPITAR00187	.	Down regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"USP7 was able to recruit DNMT1 to the FMR1 promoter region, which increased promoter methylation rates and suppressed FMR1 expression. TBK1 interacts with FMR1 to suppresses ferroptosis in renal tubular epithelial cells, manifested by decreased iron ion content and oxidative stress and increased cell viability and Phospholipid hydroperoxide glutathione peroxidase GPX4 (GPX4) expression level, thus alleviating I/R-induced renal injury"	M6ADIS0038	36264362	.
M6ACROT02054	REG00030	.	DNA methylation	EPIREG00027	EPITAR00188	.	.	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"Because IGFBP3 is an established target of DNMT3A, we investigated the effect of MTA1 upon IGFBP3 expression, and found a coactivator role of MTA1/c-Jun/Pol II coactivator complex upon the IGFBP3 transcription. In addition, MTA1 overexpression correlates well with low levels of DNMT3A which, in turn also correlates with a high IGFBP3 status in breast cancer patients and predicts a poor clinical outcome for breast cancer patients. "	M6ADIS0065	28393842	.
M6ACROT02055	REG00030	.	DNA methylation	EPIREG00027	EPITAR00188	.	.	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"By contrast, the transcription of CDH6 and IGFBP3 was triggered by HBx through the deprivation of DNMT3A from their promoters. Transcriptional levels of target genes in hepatocellular carcinoma (HCC) specimens were strongly correlated with the occurrence of HBx."	M6ADIS0006	19070387	.
M6ACROT02056	REG00030	.	DNA methylation	EPIREG00028	EPITAR00189	.	.	DNA methylation	Indirect	Inhibition	m6A	DNA methylation indirectly regulates m6A modification through downstream signaling pathways	"Functionally, Homeobox D10 (HOXD10) acts as a tumor suppressor gene, in which HOXD10-expressing cells showed suppressed cell proliferation, colony formation ability, and migration and invasion capacity. Mechanistically, DNMT1, DNMT3B, and MeCP2 were recruited in the HOXD10 promoter, and demethylation by 5-Aza-2'-deoxycytidine (5-Aza-CdR) treatment or MeCP2 knockdown can sufficiently induce HOXD10 expression. HOXD10regulates the expressions of miR-7 and IGFBP3 in a promoter-dependent manner. "	M6ADIS0059	34790580	M6ADRUG0005
M6ACROT02057	REG00030	.	DNA methylation	EPIREG00029	EPITAR00189	.	.	DNA methylation	Indirect	Inhibition	m6A	DNA methylation indirectly regulates m6A modification through downstream signaling pathways	"Functionally, Homeobox D10 (HOXD10) acts as a tumor suppressor gene, in which HOXD10-expressing cells showed suppressed cell proliferation, colony formation ability, and migration and invasion capacity. Mechanistically, DNMT1, DNMT3B, and MeCP2 were recruited in the HOXD10 promoter, and demethylation by 5-Aza-2'-deoxycytidine (5-Aza-CdR) treatment or MeCP2 knockdown can sufficiently induce HOXD10 expression. HOXD10regulates the expressions of miR-7 and IGFBP3 in a promoter-dependent manner. "	M6ADIS0059	34790580	M6ADRUG0005
M6ACROT02058	REG00007	M6ATAR00485	DNA methylation	EPIREG00027	EPITAR00027	.	Up regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"Methyltransferase-like 3 (METTL3) increased the pri-microRNA let-7b (MIRLET7B), decreased both the pre-Let-7b and mature Let-7b, attenuating the Let-7b controlling of stem cell renewal. The addition of Metformin increased the bindings of DNA methyltransferase-3a/b (DNMT3A/DNMT3B) to the METTL3 promoter. With the help of the readers of NKAP and HNRNPA2B1, the cluster mediated m6A formation on pri-Let-7b processing increased the mature Let-7b, the key player in suppressing Notch signaling and re-captivating Osimertinib treatment. "	M6ADIS0007	35070958	M6ADRUG0007
M6ACROT02059	REG00019	M6ATAR00485	DNA methylation	EPIREG00027	EPITAR00027	.	Up regulation	DNA methylation	Indirect	Inhibition	m6A	DNA methylation indirectly regulates m6A modification through downstream signaling pathways	"Methyltransferase-like 3 (Methyltransferase-like protein 3 (METTL3)) increased the pri-microRNA let-7b (MIRLET7B), decreased both the pre-Let-7b and mature Let-7b, attenuating the Let-7b controlling of stem cell renewal. The addition of Metformin increased the bindings of DNA methyltransferase-3a/b (DNMT3A/DNMT3B) to the METTL3 promoter. With the help of the readers of NKAP and HNRNPA2B1, the cluster mediated m6A formation on pri-Let-7b processing increased the mature Let-7b, the key player in suppressing Notch signaling and re-captivating Osimertinib treatment. "	M6ADIS0007	35070958	M6ADRUG0007
M6ACROT02060	REG00004	M6ATAR00485	DNA methylation	EPIREG00027	EPITAR00027	.	Up regulation	DNA methylation	Indirect	Inhibition	m6A	DNA methylation indirectly regulates m6A modification through downstream signaling pathways	"Methyltransferase-like 3 (Methyltransferase-like protein 3 (METTL3)) increased the pri-microRNA let-7b (MIRLET7B), decreased both the pre-Let-7b and mature Let-7b, attenuating the Let-7b controlling of stem cell renewal. The addition of Metformin increased the bindings of DNA methyltransferase-3a/b (DNMT3A/DNMT3B) to the METTL3 promoter. With the help of the readers of NKAP and HNRNPA2B1, the cluster mediated m6A formation on pri-Let-7b processing increased the mature Let-7b, the key player in suppressing Notch signaling and re-captivating Osimertinib treatment. "	M6ADIS0007	35070958	M6ADRUG0007
M6ACROT02061	REG00007	M6ATAR00485	DNA methylation	EPIREG00029	EPITAR00027	.	Up regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"Methyltransferase-like 3 (METTL3) increased the pri-microRNA let-7b (MIRLET7B), decreased both the pre-Let-7b and mature Let-7b, attenuating the Let-7b controlling of stem cell renewal. The addition of Metformin increased the bindings of DNA methyltransferase-3a/b (DNMT3A/DNMT3B) to the METTL3 promoter. With the help of the readers of NKAP and HNRNPA2B1, the cluster mediated m6A formation on pri-Let-7b processing increased the mature Let-7b, the key player in suppressing Notch signaling and re-captivating Osimertinib treatment. "	M6ADIS0007	35070958	M6ADRUG0007
M6ACROT02062	REG00019	M6ATAR00485	DNA methylation	EPIREG00029	EPITAR00027	.	Up regulation	DNA methylation	Indirect	Inhibition	m6A	DNA methylation indirectly regulates m6A modification through downstream signaling pathways	"Methyltransferase-like 3 (Methyltransferase-like protein 3 (METTL3)) increased the pri-microRNA let-7b (MIRLET7B), decreased both the pre-Let-7b and mature Let-7b, attenuating the Let-7b controlling of stem cell renewal. The addition of Metformin increased the bindings of DNA methyltransferase-3a/b (DNMT3A/DNMT3B) to the METTL3 promoter. With the help of the readers of NKAP and HNRNPA2B1, the cluster mediated m6A formation on pri-Let-7b processing increased the mature Let-7b, the key player in suppressing Notch signaling and re-captivating Osimertinib treatment. "	M6ADIS0007	35070958	M6ADRUG0007
M6ACROT02063	REG00004	M6ATAR00485	DNA methylation	EPIREG00029	EPITAR00027	.	Up regulation	DNA methylation	Indirect	Inhibition	m6A	DNA methylation indirectly regulates m6A modification through downstream signaling pathways	"Methyltransferase-like 3 (Methyltransferase-like protein 3 (METTL3)) increased the pri-microRNA let-7b (MIRLET7B), decreased both the pre-Let-7b and mature Let-7b, attenuating the Let-7b controlling of stem cell renewal. The addition of Metformin increased the bindings of DNA methyltransferase-3a/b (DNMT3A/DNMT3B) to the METTL3 promoter. With the help of the readers of NKAP and HNRNPA2B1, the cluster mediated m6A formation on pri-Let-7b processing increased the mature Let-7b, the key player in suppressing Notch signaling and re-captivating Osimertinib treatment. "	M6ADIS0007	35070958	M6ADRUG0007
M6ACROT02064	REG00007	M6ATAR00485	DNA methylation	EPIREG00027	EPITAR00027	.	Up regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"Methyltransferase-like 3 (METTL3) increased the pri-microRNA let-7b (MIRLET7B), decreased both the pre-Let-7b and mature Let-7b, attenuating the Let-7b controlling of stem cell renewal. The addition of Metformin increased the bindings of DNA methyltransferase-3a/b (DNMT3A/DNMT3B) to the METTL3 promoter. With the help of the readers of NKAP and HNRNPA2B1, the cluster mediated m6A formation on pri-Let-7b processing increased the mature Let-7b, the key player in suppressing Notch signaling and re-captivating Osimertinib treatment. "	M6ADIS0007	35070958	M6ADRUG0090
M6ACROT02065	REG00019	M6ATAR00485	DNA methylation	EPIREG00027	EPITAR00027	.	Up regulation	DNA methylation	Indirect	Inhibition	m6A	DNA methylation indirectly regulates m6A modification through downstream signaling pathways	"Methyltransferase-like 3 (Methyltransferase-like protein 3 (METTL3)) increased the pri-microRNA let-7b (MIRLET7B), decreased both the pre-Let-7b and mature Let-7b, attenuating the Let-7b controlling of stem cell renewal. The addition of Metformin increased the bindings of DNA methyltransferase-3a/b (DNMT3A/DNMT3B) to the METTL3 promoter. With the help of the readers of NKAP and HNRNPA2B1, the cluster mediated m6A formation on pri-Let-7b processing increased the mature Let-7b, the key player in suppressing Notch signaling and re-captivating Osimertinib treatment. "	M6ADIS0007	35070958	M6ADRUG0090
M6ACROT02066	REG00004	M6ATAR00485	DNA methylation	EPIREG00027	EPITAR00027	.	Up regulation	DNA methylation	Indirect	Inhibition	m6A	DNA methylation indirectly regulates m6A modification through downstream signaling pathways	"Methyltransferase-like 3 (Methyltransferase-like protein 3 (METTL3)) increased the pri-microRNA let-7b (MIRLET7B), decreased both the pre-Let-7b and mature Let-7b, attenuating the Let-7b controlling of stem cell renewal. The addition of Metformin increased the bindings of DNA methyltransferase-3a/b (DNMT3A/DNMT3B) to the METTL3 promoter. With the help of the readers of NKAP and HNRNPA2B1, the cluster mediated m6A formation on pri-Let-7b processing increased the mature Let-7b, the key player in suppressing Notch signaling and re-captivating Osimertinib treatment. "	M6ADIS0007	35070958	M6ADRUG0090
M6ACROT02067	REG00007	M6ATAR00485	DNA methylation	EPIREG00029	EPITAR00027	.	Up regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"Methyltransferase-like 3 (METTL3) increased the pri-microRNA let-7b (MIRLET7B), decreased both the pre-Let-7b and mature Let-7b, attenuating the Let-7b controlling of stem cell renewal. The addition of Metformin increased the bindings of DNA methyltransferase-3a/b (DNMT3A/DNMT3B) to the METTL3 promoter. With the help of the readers of NKAP and HNRNPA2B1, the cluster mediated m6A formation on pri-Let-7b processing increased the mature Let-7b, the key player in suppressing Notch signaling and re-captivating Osimertinib treatment. "	M6ADIS0007	35070958	M6ADRUG0090
M6ACROT02068	REG00019	M6ATAR00485	DNA methylation	EPIREG00029	EPITAR00027	.	Up regulation	DNA methylation	Indirect	Inhibition	m6A	DNA methylation indirectly regulates m6A modification through downstream signaling pathways	"Methyltransferase-like 3 (Methyltransferase-like protein 3 (METTL3)) increased the pri-microRNA let-7b (MIRLET7B), decreased both the pre-Let-7b and mature Let-7b, attenuating the Let-7b controlling of stem cell renewal. The addition of Metformin increased the bindings of DNA methyltransferase-3a/b (DNMT3A/DNMT3B) to the METTL3 promoter. With the help of the readers of NKAP and HNRNPA2B1, the cluster mediated m6A formation on pri-Let-7b processing increased the mature Let-7b, the key player in suppressing Notch signaling and re-captivating Osimertinib treatment. "	M6ADIS0007	35070958	M6ADRUG0090
M6ACROT02069	REG00004	M6ATAR00485	DNA methylation	EPIREG00029	EPITAR00027	.	Up regulation	DNA methylation	Indirect	Inhibition	m6A	DNA methylation indirectly regulates m6A modification through downstream signaling pathways	"Methyltransferase-like 3 (Methyltransferase-like protein 3 (METTL3)) increased the pri-microRNA let-7b (MIRLET7B), decreased both the pre-Let-7b and mature Let-7b, attenuating the Let-7b controlling of stem cell renewal. The addition of Metformin increased the bindings of DNA methyltransferase-3a/b (DNMT3A/DNMT3B) to the METTL3 promoter. With the help of the readers of NKAP and HNRNPA2B1, the cluster mediated m6A formation on pri-Let-7b processing increased the mature Let-7b, the key player in suppressing Notch signaling and re-captivating Osimertinib treatment. "	M6ADIS0007	35070958	M6ADRUG0090
M6ACROT02070	REG00002	M6ATAR01491	DNA methylation	EPIREG00027	EPITAR00190	.	Up regulation	m6A	Direct	Enhancement	DNA methylation	m6A modification directly impacts DNA methylation through modulating the expression level of DNA methyltransferases or demethylases. 	This study suggests that ELAVL1 regulates Cysteine methyltransferase DNMT3A (DNMT3A) expression and nuclear translocation to modulate dendritic cell function and Th17/Treg balance through Dachshund family transcription factor 1 (DACH1)/c-Jun pathway in COPD.	M6ADIS0268	40086625	.
M6ACROT02071	REG00008	M6ATAR01491	DNA methylation	EPIREG00027	EPITAR00190	.	Down regulation	m6A	Direct	Inhibition	DNA methylation	m6A modification directly impacts DNA methylation through modulating the expression level of DNA methyltransferases or demethylases. 	This study suggests that YTHDF2 regulates Cysteine methyltransferase DNMT3A (DNMT3A) expression and nuclear translocation to modulate dendritic cell function and Th17/Treg balance through Dachshund family transcription factor 1 (DACH1)/c-Jun pathway in COPD.	M6ADIS0268	40086625	.
M6ACROT02072	REG00002	M6ATAR00658	DNA methylation	EPIREG00029	.	.	Up regulation	m6A	Direct	Enhancement	DNA methylation	m6A modification directly impacts DNA methylation through modulating the expression level of DNA methyltransferases or demethylases. 	"These studies revealed that binding of HuR (ELAVL1) stabilized the DNA (cytosine-5)-methyltransferase 3B (DNMT3B) mRNA and increased DNMT3b expression. Unexpectedly, cisplatin treatment triggered the dissociation of the [HuR-DNMT3b mRNA] complex, in turn promoting DNMT3b mRNA decay, decreasing DNMT3b abundance, and lowering the methylation of repeated sequences and global DNA methylation. In summary, our data identify DNMT3b mRNA as a novel HuR target, present evidence that HuR affects DNMT3b expression levels post-transcriptionally, and reveal the functional consequences of the HuR-regulated DNMT3b upon DNA methylation patterns."	.	19270063	M6ADRUG0047
M6ACROT02073	REG00002	M6ATAR00658	DNA methylation	EPIREG00029	EPITAR00191	.	Up regulation	m6A	Direct	Enhancement	DNA methylation	m6A modification directly impacts DNA methylation through modulating the expression level of DNA methyltransferases or demethylases. 	"ELAVL1 plays a critical role in protecting against ferroptosis-induced cerebral I/R and subsequent brain damage via DNA (cytosine-5)-methyltransferase 3B (DNMT3B)/Serine/threonine-protein kinase PINK1, mitochondrial (PINK1) axis, thus providing a new potential target for ischemic stroke treatment."	M6ADIS0091	36173508	.
M6ACROT02074	REG00024	M6ATAR00658	DNA methylation	EPIREG00029	.	.	Up regulation	m6A	Direct	Enhancement	DNA methylation	m6A modification directly impacts DNA methylation through modulating the expression level of DNA methyltransferases or demethylases. 	"Furthermore, methylated RNA immunoprecipitation and RNA Immunoprecipitation assays revealed that YTHDF1 elevated the expression of DNA (cytosine-5)-methyltransferase 3B (DNMT3B), which synergistically promoted the initiation and development of GC. We elucidated the molecular mechanism underlying the regulation of DNMT3B by YTHDF1 and explored the crosstalk between m6A and 5mC modification."	M6ADIS0057	39185313	.
M6ACROT02075	REG00012	M6ATAR00341	DNA methylation	EPIREG00027	EPITAR00192	.	Up regulation	DNA methylation	Indirect	Inhibition	m6A	DNA methylation indirectly regulates m6A modification through downstream signaling pathways	HBx inhibited Protein tyrosine phosphatase non-receptor type 13 (PTPN13) expression by upregulating the expression of DNMT3A and interacting with DNMT3A. we identified IGF2BP1 as a novel PTPN13-interacting gene and demonstrated that PTPN13 influences Myc proto-oncogene protein (MYC) expression by directly and competitively binding to IGF2BP1 to decrease the intracellular concentration of functional IGF2BP1. Overexpressing PTPN13 promoted c-Myc mRNA degradation independent of the protein tyrosine phosphatase (PTP) activity of PTPN13.	M6ADIS0006	33051595	.
M6ACROT02076	REG00007	M6ATAR01491	DNA methylation	EPIREG00027	EPITAR00193	.	Up regulation	m6A	Direct	Enhancement	DNA methylation	m6A modification directly impacts DNA methylation through modulating the expression level of DNA methyltransferases or demethylases. 	"The mechanistic study showed that that METTL3 ablation attenuated the m6A modification in Cysteine methyltransferase DNMT3A (DNMT3A) mRNAs and consequently impaired YTHDF1-mediated translation of DNMT3A. We identified that DNMT3A bound to the promoter region of Alpha tubulin acetyltransferase 1 (ATAT1) and maintained its expression. METTL3 depletion resulted in the down-regulation of ATAT1, reduced acetylation of alpha-tubulin and subsequently enhanced migration of monocyte-derived macrophages and Abeta clearance, which led to the alleviated symptoms of AD."	M6ADIS0089	36881554	.
M6ACROT02077	REG00024	M6ATAR01491	DNA methylation	EPIREG00027	EPITAR00193	.	Up regulation	m6A	Direct	Enhancement	DNA methylation	m6A modification directly impacts DNA methylation through modulating the expression level of DNA methyltransferases or demethylases. 	"The mechanistic study showed that that METTL3 ablation attenuated the m6A modification in Cysteine methyltransferase DNMT3A (DNMT3A) mRNAs and consequently impaired YTHDF1-mediated translation of DNMT3A. We identified that DNMT3A bound to the promoter region of Alpha tubulin acetyltransferase 1 (ATAT1) and maintained its expression. METTL3 depletion resulted in the down-regulation of ATAT1, reduced acetylation of alpha-tubulin and subsequently enhanced migration of monocyte-derived macrophages and Abeta clearance, which led to the alleviated symptoms of AD."	M6ADIS0089	36881554	.
M6ACROT02078	REG00001	M6ATAR01573	DNA methylation	EPIREG00028	EPITAR00179	.	.	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"A downregulation in demethylating enzyme Fto and upregulation in methylating enzyme Mettl3 were also noted. The FTO promoter was hypomethylated due to the lower expression of DNMT1 and DNMT3A and Glucocorticoid receptor (NR3C1), Creb1, Ntrk2, Bdnf are downstream target genes of both METTL3 and FTO."	M6ADIS0370	36161325	.
M6ACROT02079	REG00001	M6ATAR00833	DNA methylation	EPIREG00028	EPITAR00179	.	.	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"A downregulation in demethylating enzyme Fto and upregulation in methylating enzyme Mettl3 were also noted. The FTO promoter was hypomethylated due to the lower expression of DNMT1 and DNMT3A and Nr3c1, Cyclic AMP-responsive element-binding protein 1 (CREB1), Ntrk2, Bdnf are downstream target genes of both METTL3 and FTO."	M6ADIS0370	36161325	.
M6ACROT02080	REG00001	M6ATAR01574	DNA methylation	EPIREG00028	EPITAR00179	.	.	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"A downregulation in demethylating enzyme Fto and upregulation in methylating enzyme Mettl3 were also noted. The FTO promoter was hypomethylated due to the lower expression of DNMT1 and DNMT3A and Nr3c1, Creb1, BDNF/NT-3 growth factors receptor (NTRK2), Bdnf are downstream target genes of both METTL3 and FTO."	M6ADIS0370	36161325	.
M6ACROT02081	REG00001	M6ATAR00844	DNA methylation	EPIREG00028	EPITAR00179	.	.	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"A downregulation in demethylating enzyme Fto and upregulation in methylating enzyme Mettl3 were also noted. The FTO promoter was hypomethylated due to the lower expression of DNMT1 and DNMT3A and Nr3c1, Creb1, Ntrk2, Neurotrophic factor BDNF precursor form (BDNF) are downstream target genes of both METTL3 and FTO."	M6ADIS0370	36161325	.
M6ACROT02082	REG00001	M6ATAR01573	DNA methylation	EPIREG00027	EPITAR00179	.	.	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"A downregulation in demethylating enzyme Fto and upregulation in methylating enzyme Mettl3 were also noted. The FTO promoter was hypomethylated due to the lower expression of DNMT1 and DNMT3A and Glucocorticoid receptor (NR3C1), Creb1, Ntrk2, Bdnf are downstream target genes of both METTL3 and FTO."	M6ADIS0370	36161325	.
M6ACROT02083	REG00001	M6ATAR00833	DNA methylation	EPIREG00027	EPITAR00179	.	.	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"A downregulation in demethylating enzyme Fto and upregulation in methylating enzyme Mettl3 were also noted. The FTO promoter was hypomethylated due to the lower expression of DNMT1 and DNMT3A and Nr3c1, Cyclic AMP-responsive element-binding protein 1 (CREB1), Ntrk2, Bdnf are downstream target genes of both METTL3 and FTO."	M6ADIS0370	36161325	.
M6ACROT02084	REG00001	M6ATAR01574	DNA methylation	EPIREG00027	EPITAR00179	.	.	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"A downregulation in demethylating enzyme Fto and upregulation in methylating enzyme Mettl3 were also noted. The FTO promoter was hypomethylated due to the lower expression of DNMT1 and DNMT3A and Nr3c1, Creb1, BDNF/NT-3 growth factors receptor (NTRK2), Bdnf are downstream target genes of both METTL3 and FTO."	M6ADIS0370	36161325	.
M6ACROT02085	REG00001	M6ATAR00844	DNA methylation	EPIREG00027	EPITAR00179	.	.	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"A downregulation in demethylating enzyme Fto and upregulation in methylating enzyme Mettl3 were also noted. The FTO promoter was hypomethylated due to the lower expression of DNMT1 and DNMT3A and Nr3c1, Creb1, Ntrk2, Neurotrophic factor BDNF precursor form (BDNF) are downstream target genes of both METTL3 and FTO."	M6ADIS0370	36161325	.
M6ACROT02086	REG00007	M6ATAR01573	DNA methylation	EPIREG00028	EPITAR00179	.	.	DNA methylation	Indirect	Enhancement	m6A	DNA methylation indirectly regulates m6A modification through downstream signaling pathways	"A downregulation in demethylating enzyme Fto and upregulation in methylating enzyme Mettl3 were also noted. The FTO alpha-ketoglutarate dependent dioxygenase (FTO) promoter was hypomethylated due to the lower expression of DNMT1 and DNMT3A and Glucocorticoid receptor (NR3C1), Creb1, Ntrk2, Bdnf are downstream target genes of both METTL3 and FTO."	M6ADIS0370	36161325	.
M6ACROT02087	REG00007	M6ATAR00833	DNA methylation	EPIREG00028	EPITAR00179	.	.	DNA methylation	Indirect	Enhancement	m6A	DNA methylation indirectly regulates m6A modification through downstream signaling pathways	"A downregulation in demethylating enzyme Fto and upregulation in methylating enzyme Mettl3 were also noted. The FTO alpha-ketoglutarate dependent dioxygenase (FTO) promoter was hypomethylated due to the lower expression of DNMT1 and DNMT3A and Nr3c1, Cyclic AMP-responsive element-binding protein 1 (CREB1), Ntrk2, Bdnf are downstream target genes of both METTL3 and FTO."	M6ADIS0370	36161325	.
M6ACROT02088	REG00007	M6ATAR01574	DNA methylation	EPIREG00028	EPITAR00179	.	.	DNA methylation	Indirect	Enhancement	m6A	DNA methylation indirectly regulates m6A modification through downstream signaling pathways	"A downregulation in demethylating enzyme Fto and upregulation in methylating enzyme Mettl3 were also noted. The FTO alpha-ketoglutarate dependent dioxygenase (FTO) promoter was hypomethylated due to the lower expression of DNMT1 and DNMT3A and Nr3c1, Creb1, BDNF/NT-3 growth factors receptor (NTRK2), Bdnf are downstream target genes of both METTL3 and FTO."	M6ADIS0370	36161325	.
M6ACROT02089	REG00007	M6ATAR00844	DNA methylation	EPIREG00028	EPITAR00179	.	.	DNA methylation	Indirect	Enhancement	m6A	DNA methylation indirectly regulates m6A modification through downstream signaling pathways	"A downregulation in demethylating enzyme Fto and upregulation in methylating enzyme Mettl3 were also noted. The FTO alpha-ketoglutarate dependent dioxygenase (FTO) promoter was hypomethylated due to the lower expression of DNMT1 and DNMT3A and Nr3c1, Creb1, Ntrk2, Neurotrophic factor BDNF precursor form (BDNF) are downstream target genes of both METTL3 and FTO."	M6ADIS0370	36161325	.
M6ACROT02090	REG00007	M6ATAR01573	DNA methylation	EPIREG00027	EPITAR00179	.	.	DNA methylation	Indirect	Enhancement	m6A	DNA methylation indirectly regulates m6A modification through downstream signaling pathways	"A downregulation in demethylating enzyme Fto and upregulation in methylating enzyme Mettl3 were also noted. The FTO alpha-ketoglutarate dependent dioxygenase (FTO) promoter was hypomethylated due to the lower expression of DNMT1 and DNMT3A and Glucocorticoid receptor (NR3C1), Creb1, Ntrk2, Bdnf are downstream target genes of both METTL3 and FTO."	M6ADIS0370	36161325	.
M6ACROT02091	REG00007	M6ATAR00833	DNA methylation	EPIREG00027	EPITAR00179	.	.	DNA methylation	Indirect	Enhancement	m6A	DNA methylation indirectly regulates m6A modification through downstream signaling pathways	"A downregulation in demethylating enzyme Fto and upregulation in methylating enzyme Mettl3 were also noted. The FTO alpha-ketoglutarate dependent dioxygenase (FTO) promoter was hypomethylated due to the lower expression of DNMT1 and DNMT3A and Nr3c1, Cyclic AMP-responsive element-binding protein 1 (CREB1), Ntrk2, Bdnf are downstream target genes of both METTL3 and FTO."	M6ADIS0370	36161325	.
M6ACROT02092	REG00007	M6ATAR01574	DNA methylation	EPIREG00027	EPITAR00179	.	.	DNA methylation	Indirect	Enhancement	m6A	DNA methylation indirectly regulates m6A modification through downstream signaling pathways	"A downregulation in demethylating enzyme Fto and upregulation in methylating enzyme Mettl3 were also noted. The FTO alpha-ketoglutarate dependent dioxygenase (FTO) promoter was hypomethylated due to the lower expression of DNMT1 and DNMT3A and Nr3c1, Creb1, BDNF/NT-3 growth factors receptor (NTRK2), Bdnf are downstream target genes of both METTL3 and FTO."	M6ADIS0370	36161325	.
M6ACROT02093	REG00007	M6ATAR00844	DNA methylation	EPIREG00027	EPITAR00179	.	.	DNA methylation	Indirect	Enhancement	m6A	DNA methylation indirectly regulates m6A modification through downstream signaling pathways	"A downregulation in demethylating enzyme Fto and upregulation in methylating enzyme Mettl3 were also noted. The FTO alpha-ketoglutarate dependent dioxygenase (FTO) promoter was hypomethylated due to the lower expression of DNMT1 and DNMT3A and Nr3c1, Creb1, Ntrk2, Neurotrophic factor BDNF precursor form (BDNF) are downstream target genes of both METTL3 and FTO."	M6ADIS0370	36161325	.
M6ACROT02094	REG00007	M6ATAR00637	DNA methylation	EPIREG00020	EPITAR00067	.	Down regulation	m6A	Direct	Inhibition	DNA methylation	m6A modification directly impacts DNA methylation through modulating the expression level of DNA methyltransferases or demethylases. 	"Overexpressing METTL3 reversed a loss of m6A in Tet1 mRNA and blocked the CFA-induced increase of Methylcytosine dioxygenase TET1 (TET1) in the spinal cord, resulting in the attenuation of pain behavior, and acted as an upstream regulator of Signal transducer and activator of transcription 3 (STAT3). Furthermore, the decreased level of spinal YT521-B homology domain family protein 2 (YTHDF2), an RNA m6A reader, stabilized upregulation of spinal TET1 because of the reduction of Tet1 mRNA decay by the binding to m6A in Tet1 mRNA in the spinal cord after CFA. "	M6ADIS0024	34130310	.
M6ACROT02095	REG00008	M6ATAR00637	DNA methylation	EPIREG00020	EPITAR00067	.	Down regulation	m6A	Direct	Inhibition	DNA methylation	m6A modification directly impacts DNA methylation through modulating the expression level of DNA methyltransferases or demethylases. 	"Overexpressing Mettl3 reversed a loss of m6A in Tet1 mRNA and blocked the CFA-induced increase of Methylcytosine dioxygenase TET1 (TET1) in the spinal cord, resulting in the attenuation of pain behavior, and acted as an upstream regulator of Signal transducer and activator of transcription 3 (STAT3). Furthermore, the decreased level of spinal YT521-B homology domain family protein 2 (YTHDF2), an RNA m6A reader, stabilized upregulation of spinal TET1 because of the reduction of Tet1 mRNA decay by the binding to m6A in Tet1 mRNA in the spinal cord after CFA. "	M6ADIS0024	34130310	.
M6ACROT02097	REG00023	M6ATAR00053	DNA methylation	EPIREG00022	.	.	Up regulation	m6A	Indirect	Inhibition	DNA methylation	m6A modification indirectly regulates DNA methylation through downstream signaling pathways	YTHDC2-Mediated Circ_YTHDC2 N6-Methyladenosine Modification Promotes Vascular Smooth Muscle Cells Dysfunction Through Inhibiting TET2.	M6ADIS0077	34660707	.
M6ACROT02098	REG00007	M6ATAR01381	DNA methylation	EPIREG00020	EPITAR00194	.	Up regulation	m6A	Indirect	Enhancement	DNA methylation	m6A modification indirectly regulates DNA methylation through downstream signaling pathways	"METTL3 and METTL14-induced m6A modification upregulated Sterol regulatory element binding transcription factor 2 (SREBF2) antisense RNA 1 (SREBF2-AS1) expression through increasing SREBF2-AS1 transcript stability. Mechanistic investigations revealed that m6A-modified SREBF2-AS1 bound and recruited m6A reader FXR1 and DNA 5-methylcytosine dioxygenase TET1 to SREBF2 promoter, leading to DNA demethylation at SREBF2 promoter and the upregulation of SREBF2 transcription. Together, this study showed that m6A-modified SREBF2-AS1 exerted oncogenic roles in HCC through inducing DNA demethylation and transcriptional activation of SREBF2, and suggested m6A-modified SREBF2-AS1 as a prognostic biomarker and therapeutic target for HCC."	M6ADIS0006	38486042	.
M6ACROT02099	REG00006	M6ATAR01381	DNA methylation	EPIREG00020	EPITAR00194	.	Up regulation	m6A	Indirect	Enhancement	DNA methylation	m6A modification indirectly regulates DNA methylation through downstream signaling pathways	"METTL3 and METTL14-induced m6A modification upregulated Sterol regulatory element binding transcription factor 2 (SREBF2) antisense RNA 1 (SREBF2-AS1) expression through increasing SREBF2-AS1 transcript stability. Mechanistic investigations revealed that m6A-modified SREBF2-AS1 bound and recruited m6A reader FXR1 and DNA 5-methylcytosine dioxygenase TET1 to SREBF2 promoter, leading to DNA demethylation at SREBF2 promoter and the upregulation of SREBF2 transcription. Together, this study showed that m6A-modified SREBF2-AS1 exerted oncogenic roles in HCC through inducing DNA demethylation and transcriptional activation of SREBF2, and suggested m6A-modified SREBF2-AS1 as a prognostic biomarker and therapeutic target for HCC."	M6ADIS0006	38486042	.
M6ACROT02100	REG00051	M6ATAR01381	DNA methylation	EPIREG00020	EPITAR00194	.	Up regulation	m6A	Direct	Enhancement	DNA methylation	m6A modification directly impacts DNA methylation through recruiting DNA methyltransferases or demethylases. 	"METTL3 and METTL14-induced m6A modification upregulated Sterol regulatory element binding transcription factor 2 (SREBF2) antisense RNA 1 (SREBF2-AS1) expression through increasing SREBF2-AS1 transcript stability. Mechanistic investigations revealed that m6A-modified SREBF2-AS1 bound and recruited m6A reader FXR1 and DNA 5-methylcytosine dioxygenase TET1 to SREBF2 promoter, leading to DNA demethylation at SREBF2 promoter and the upregulation of SREBF2 transcription. Together, this study showed that m6A-modified SREBF2-AS1 exerted oncogenic roles in HCC through inducing DNA demethylation and transcriptional activation of SREBF2, and suggested m6A-modified SREBF2-AS1 as a prognostic biomarker and therapeutic target for HCC."	M6ADIS0006	38486042	.
M6ACROT02101	REG00006	M6ATAR00118	DNA methylation	EPIREG00027	EPITAR00195	.	Down regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"lncRNA UCA1 recruited DNA methyltransferase (DNMT1, DNMT3A, and DNMT3B) to the METTL14 promoter region to inhibit METTL14 expression in breast cancer. silencing lncRNA UCA1 curbed the progression of breast cancer through the METTL14-microRNA 375 (MIR375)-SOX12 axis."	M6ADIS0065	35022519	.
M6ACROT02102	REG00006	M6ATAR00118	DNA methylation	EPIREG00029	EPITAR00195	.	Down regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"lncRNA UCA1 recruited DNA methyltransferase (DNMT1, DNMT3A, and DNMT3B) to the METTL14 promoter region to inhibit METTL14 expression in breast cancer. silencing lncRNA UCA1 curbed the progression of breast cancer through the METTL14-microRNA 375 (MIR375)-SOX12 axis."	M6ADIS0065	35022519	.
M6ACROT02103	REG00006	M6ATAR00118	DNA methylation	EPIREG00028	EPITAR00195	.	Down regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"lncRNA UCA1 recruited DNA methyltransferase (DNMT1, DNMT3A, and DNMT3B) to the METTL14 promoter region to inhibit METTL14 expression in breast cancer. silencing lncRNA UCA1 curbed the progression of breast cancer through the METTL14-microRNA 375 (MIR375)-SOX12 axis."	M6ADIS0065	35022519	.
M6ACROT02104	REG00009	M6ATAR01576	DNA methylation	.	EPITAR00196	.	Up regulation	DNA methylation	Indirect	Inhibition	m6A	DNA methylation indirectly regulates m6A modification through downstream signaling pathways	"These data indicated that hsa-miR-550-1 might mediate a decrease in m6A levels via targeting WTAP, which led to a further reduction in WW domain-containing transcription regulator protein 1 (WWTR1) stability. Using gain- and loss-of-function approaches, we were able to determine that miR-550-1 disrupted the proliferation and tumorigenesis of AML cells at least in part via the direct targeting of WWTR1. "	M6ADIS0046	33061801	.
M6ACROT02106	REG00007	M6ATAR01491	DNA methylation	EPIREG00027	.	.	Up regulation	m6A	Direct	Enhancement	DNA methylation	m6A modification directly impacts DNA methylation through modulating the expression level of DNA methyltransferases or demethylases. 	"Linc00942 recruits RNA methyltransferase METTL3 to stimulate N6-methyladenosine (m6A) deposit on Cysteine methyltransferase DNMT3A (DNMT3A) transcripts, triggering IGF2BP3/HuR to recognize modified mRNA for reinforced stability. SQSTM1/p62 recruits Linc00942 for autophagic degradation which can be abrogated after autophagy inhibition by p62 knockdown or chloroquine treatment."	M6ADIS0057	37477089	M6ADRUG0252
M6ACROT02107	REG00014	M6ATAR01491	DNA methylation	EPIREG00027	.	.	Up regulation	m6A	Direct	Enhancement	DNA methylation	m6A modification directly impacts DNA methylation through modulating the expression level of DNA methyltransferases or demethylases. 	"Linc00942 recruits RNA methyltransferase METTL3 to stimulate N6-methyladenosine (m6A) deposit on Cysteine methyltransferase DNMT3A (DNMT3A) transcripts, triggering IGF2BP3/HuR to recognize modified mRNA for reinforced stability. SQSTM1/p62 recruits Linc00942 for autophagic degradation which can be abrogated after autophagy inhibition by p62 knockdown or chloroquine treatment."	M6ADIS0057	37477089	M6ADRUG0252
M6ACROT02108	REG00024	M6ATAR01577	DNA methylation	EPIREG00030	EPITAR00197	.	Up regulation	m6A	Direct	Enhancement	DNA methylation	m6A modification directly impacts DNA methylation through modulating the expression level of DNA methyltransferases or demethylases. 	"YTHDF1 recognizes target Methyl-CpG-binding protein 2 (MECP2) mRNA and induces its translation. Solute carrier family 31 member 1 (SLC31A1) inhibition due to increased MeCP2-recognized methylating CpG islands of SLC31A1 in the promoter region restrains its transcription. Conversely, MeCP2 knockdown rescued SLC31A1 expression, resulting in contradictory effects."	M6ADIS0375	40048660	.
M6ACROT02109	REG00051	M6ATAR01578	DNA methylation	EPIREG00020	EPITAR00198	.	.	m6A	Direct	Enhancement	DNA methylation	m6A modification directly impacts DNA methylation through recruiting DNA methyltransferases or demethylases. 	"MIR670 host gene (MIR670HG) interacts with the m6A reader FXR1 and DNA 5-methylcytosine dioxygenase TET1 in an m6A modification-dependent manner. These interactions reduce the binding of TET1 to CD24 molecule (CD24) promoter, leading to increased DNA methylation at CD24 promoter and transcriptional suppression of CD24."	M6ADIS0326	40293529	.
M6ACROT02110	REG00005	M6ATAR00186	DNA methylation	.	EPITAR00183	.	Down regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"Folic acid reduces the expression of ALKHB5 via promoter DNA hypermethylation. Decreased ALKBH5 causes increased m6A modification and increased expression of Ubiquitin-like protein ATG12 (ATG12) in a demethylase activity-dependent manner, thereby promoting autophagy and preventing hepatic steatosis."	M6ADIS0107	39993647	.
M6ACROT02111	REG00001	M6ATAR01579	DNA methylation	EPIREG00029	EPITAR00065	.	Up regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation regulates m6A modification through both regulatory proteins targeting the same gene.	"Insulin-like growth factor-binding protein 7 (IGFBP7) is regulated by DNA methylation at the genetic level, which is modulated by DNMT3B and DNMT1, and by the RNA m6A demethylase FTO at the posttranscriptional level."	M6ADIS0057	39351597	.
M6ACROT02112	REG00001	M6ATAR01579	DNA methylation	EPIREG00028	EPITAR00065	.	Up regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation regulates m6A modification through both regulatory proteins targeting the same gene.	"Insulin-like growth factor-binding protein 7 (IGFBP7) is regulated by DNA methylation at the genetic level, which is modulated by DNMT3B and DNMT1, and by the RNA m6A demethylase FTO at the posttranscriptional level."	M6ADIS0057	39351597	.
M6ACROT02113	REG00007	M6ATAR01580	DNA methylation	EPIREG00022	EPITAR00200	.	Up regulation	DNA methylation	Direct	Enhancement	m6A	DNA methylation regulates m6A modification through both regulatory proteins targeting the same gene.	"The suppression of 5mC demethylation or m6A hypermethylation significantly alleviates the upregulation of Phosphoenolpyruvate carboxykinase [GTP], mitochondrial (PCK2) and proinflammatory cytokines in LPS-challenged KCs. Further reciprocal tests indicate TET2-mediated 5mC demethylation is upstream of m6A hypermethylation. Specifically, CpG islands in the promoters of PCK2 and RNA methyltransferase (METTL3 and METTL14) genes are demethylated, while the 3'UTR of PCK2 mRNA is m6A hypermethylated, in LPS-stimulated KCs. These modifications contribute to the transactivation of the PCK2 gene as well as increased PCK2 mRNA stability and protein production via a m6A-mediated mechanism with IGF2BP1 as the reader protein. These results indicate that DNA 5mC and RNA m6A collaborate to upregulate PCK2 expression, respectively, at the transcriptional and post-transcriptional levels during KC activation."	M6ADIS0335	39337381	.
M6ACROT02114	REG00006	M6ATAR01580	DNA methylation	EPIREG00022	EPITAR00200	.	Up regulation	DNA methylation	Direct	Enhancement	m6A	DNA methylation regulates m6A modification through both regulatory proteins targeting the same gene.	"The suppression of 5mC demethylation or m6A hypermethylation significantly alleviates the upregulation of Phosphoenolpyruvate carboxykinase [GTP], mitochondrial (PCK2) and proinflammatory cytokines in LPS-challenged KCs. Further reciprocal tests indicate TET2-mediated 5mC demethylation is upstream of m6A hypermethylation. Specifically, CpG islands in the promoters of PCK2 and RNA methyltransferase (METTL3 and METTL14) genes are demethylated, while the 3'UTR of PCK2 mRNA is m6A hypermethylated, in LPS-stimulated KCs. These modifications contribute to the transactivation of the PCK2 gene as well as increased PCK2 mRNA stability and protein production via a m6A-mediated mechanism with IGF2BP1 as the reader protein. These results indicate that DNA 5mC and RNA m6A collaborate to upregulate PCK2 expression, respectively, at the transcriptional and post-transcriptional levels during KC activation."	M6ADIS0335	39337381	.
M6ACROT02115	REG00012	M6ATAR01580	DNA methylation	EPIREG00022	EPITAR00200	.	Up regulation	DNA methylation	Direct	Enhancement	m6A	DNA methylation regulates m6A modification through both regulatory proteins targeting the same gene.	"The suppression of 5mC demethylation or m6A hypermethylation significantly alleviates the upregulation of Phosphoenolpyruvate carboxykinase [GTP], mitochondrial (PCK2) and proinflammatory cytokines in LPS-challenged KCs. Further reciprocal tests indicate TET2-mediated 5mC demethylation is upstream of m6A hypermethylation. Specifically, CpG islands in the promoters of PCK2 and RNA methyltransferase (METTL3 and METTL14) genes are demethylated, while the 3'UTR of PCK2 mRNA is m6A hypermethylated, in LPS-stimulated KCs. These modifications contribute to the transactivation of the PCK2 gene as well as increased PCK2 mRNA stability and protein production via a m6A-mediated mechanism with IGF2BP1 as the reader protein. These results indicate that DNA 5mC and RNA m6A collaborate to upregulate PCK2 expression, respectively, at the transcriptional and post-transcriptional levels during KC activation."	M6ADIS0335	39337381	.
M6ACROT02116	REG00007	M6ATAR00099	DNA methylation	EPIREG00028	EPITAR00027	.	Up regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"Quantitative chromatin immunoprecipitation (ChIP) assays showed that CSC substantially reduced the bindings of DNA methyltransferase 1 (DNMT1) and DNMT3A to the METTL3 promoter. METTL3 induced m6A hyper-methylation on the 3' UTR of LIFR antisense RNA 1 (LIFR antisense RNA 1 (LIFR-AS1)) to enhance its mRNA stability and LIFR-AS1 could directly interact with miR-150-5p, thereby indirectly up-regulating VEGFA expressions within cells. A noval m6A-LIFR-AS1 axis promotes pancreatic cancer progression at least in part via regulation of the miR-150-5p/VEGFA axis, indicating that this regulatory axis can be a viable clinical target for the treatment of pancreatic cancer."	M6ADIS0061	31015415; 34658294	.
M6ACROT02117	REG00007	M6ATAR00791	DNA methylation	EPIREG00028	EPITAR00027	.	Up regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"Quantitative chromatin immunoprecipitation (ChIP) assays showed that CSC substantially reduced the bindings of DNA methyltransferase 1 (DNMT1) and DNMT3A to the METTL3 promoter. hsa-miR-380-3p was enriched with m6A modifications, and elimination of m6A modifications by deleting METTL3 and METTL14 synergistically suppressed miR-380-3p expressions in pancreatic cancer cells."	M6ADIS0061	31015415; 35758158	.
M6ACROT02118	REG00007	M6ATAR00711	DNA methylation	EPIREG00028	EPITAR00027	.	.	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"Quantitative chromatin immunoprecipitation (ChIP) assays showed that CSC substantially reduced the bindings of DNA methyltransferase 1 (DNMT1) and DNMT3A to the METTL3 promoter. DBH antisense RNA 1 (Lnc_DBH-AS1) expression in pancreatic cancer(PC) was found to be linked to the METTL3-dependent m6A methylation of the lncRNA. Mechanistically, lncRNA DBH-AS1 was able to increase PC cell sensitivity to gemcitabine by sequestering miR-3163 and thus upregulating USP44 in these tumor cells."	M6ADIS0061	31015415; 35433957	M6ADRUG0024
M6ACROT02119	REG00007	M6ATAR00285	DNA methylation	EPIREG00028	EPITAR00027	.	Up regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"Quantitative chromatin immunoprecipitation (ChIP) assays showed that CSC substantially reduced the bindings of DNA methyltransferase 1 (DNMT1) and DNMT3A to the METTL3 promoter. METTL3 may post-transcriptionally upregulate DNA-binding protein inhibitor ID-2 (ID2) expression in an m6A-YTHDF2-dependent manner to further promote the stabilization of ID2 mRNA, which may be a new target for pancreatic cancer treatment."	M6ADIS0061	31015415; 37196908	.
M6ACROT02120	REG00007	M6ATAR00919	DNA methylation	EPIREG00028	EPITAR00027	.	Down regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	Quantitative chromatin immunoprecipitation (ChIP) assays showed that CSC substantially reduced the bindings of DNA methyltransferase 1 (DNMT1) and DNMT3A to the METTL3 promoter. This study demonstrates the promise of BRAF-activated non-protein coding RNA (BANCR) as a new diagnostic and therapeutic target for pancreatic cancer and reveals the therapeutic effect that STM2457(METTL3) exerts on pancreatic cancer by down-regulating BANCR m6A modifications.	M6ADIS0061	31015415; 37998732	.
M6ACROT02121	REG00007	M6ATAR00944	DNA methylation	EPIREG00028	EPITAR00027	.	Up regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"Quantitative chromatin immunoprecipitation (ChIP) assays showed that CSC substantially reduced the bindings of DNA methyltransferase 1 (DNMT1) and DNMT3A to the METTL3 promoter. METTL3 was upregulated in PC tissues and cells and was associated with malignant tumor progression and poor progression-free survival in PC.Four m6A motifs were identified in Long intergenic non-protein coding RNA 662 (LINC00662), which maintained the stability of Linc00662 in an IGF2BP3-coupled manner and were closely associated with the pro-tumor properties of Linc00662 in vitro and in vivo."	M6ADIS0061	31015415; 37293163	.
M6ACROT02122	REG00007	M6ATAR00967	DNA methylation	EPIREG00028	EPITAR00027	.	Up regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"Quantitative chromatin immunoprecipitation (ChIP) assays showed that CSC substantially reduced the bindings of DNA methyltransferase 1 (DNMT1) and DNMT3A to the METTL3 promoter. celastrol treatment downregulated METTL3 and decreased m6A levels of Claspin (CLSPN) and Bcl-2 mRNA, leading to the degradation of Claspin and Bcl-2 mRNA in pancreatic cancer cells. Furthermore, we revealed that celastrol treatment downregulated Claspin and Bcl-2, at least in part, in an m6A-YTHDF3-mediated manner in pancreatic cancer cells."	M6ADIS0061	31015415; 38110764	M6ADRUG0176
M6ACROT02123	REG00007	M6ATAR00196	DNA methylation	EPIREG00028	EPITAR00027	.	Up regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"Quantitative chromatin immunoprecipitation (ChIP) assays showed that CSC substantially reduced the bindings of DNA methyltransferase 1 (DNMT1) and DNMT3A to the METTL3 promoter. celastrol treatment downregulated METTL3 and decreased m6A levels of Claspin and Apoptosis regulator Bcl-2 (BCL2) mRNA, leading to the degradation of Claspin and Bcl-2 mRNA in pancreatic cancer cells. Furthermore, we revealed that celastrol treatment downregulated Claspin and Bcl-2, at least in part, in an m6A-YTHDF3-mediated manner in pancreatic cancer cells."	M6ADIS0061	31015415; 38110764	M6ADRUG0176
M6ACROT02124	REG00007	M6ATAR00298	DNA methylation	EPIREG00028	EPITAR00027	.	.	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	Quantitative chromatin immunoprecipitation (ChIP) assays showed that CSC substantially reduced the bindings of DNA methyltransferase 1 (DNMT1) and DNMT3A to the METTL3 promoter. Hypoxia promotes immune escape of pancreatic cancer cells by lncRNA NNT-AS1/METTL3-HuR-mediated Integrin beta-1 (ITGB1) m6A modification	M6ADIS0061	31015415; 37659467	.
M6ACROT02125	REG00007	M6ATAR00099	DNA methylation	EPIREG00027	EPITAR00027	.	Up regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"Quantitative chromatin immunoprecipitation (ChIP) assays showed that CSC substantially reduced the bindings of DNA methyltransferase 1 (DNMT1) and DNMT3A to the METTL3 promoter. METTL3 induced m6A hyper-methylation on the 3' UTR of LIFR antisense RNA 1 (LIFR antisense RNA 1 (LIFR-AS1)) to enhance its mRNA stability and LIFR-AS1 could directly interact with miR-150-5p, thereby indirectly up-regulating VEGFA expressions within cells. A noval m6A-LIFR-AS1 axis promotes pancreatic cancer progression at least in part via regulation of the miR-150-5p/VEGFA axis, indicating that this regulatory axis can be a viable clinical target for the treatment of pancreatic cancer."	M6ADIS0061	31015415; 34658294	.
M6ACROT02126	REG00007	M6ATAR00791	DNA methylation	EPIREG00027	EPITAR00027	.	Up regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"Quantitative chromatin immunoprecipitation (ChIP) assays showed that CSC substantially reduced the bindings of DNA methyltransferase 1 (DNMT1) and DNMT3A to the METTL3 promoter. hsa-miR-380-3p was enriched with m6A modifications, and elimination of m6A modifications by deleting METTL3 and METTL14 synergistically suppressed miR-380-3p expressions in pancreatic cancer cells."	M6ADIS0061	31015415; 35758158	.
M6ACROT02127	REG00007	M6ATAR00711	DNA methylation	EPIREG00027	EPITAR00027	.	.	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"Quantitative chromatin immunoprecipitation (ChIP) assays showed that CSC substantially reduced the bindings of DNA methyltransferase 1 (DNMT1) and DNMT3A to the METTL3 promoter. DBH antisense RNA 1 (Lnc_DBH-AS1) expression in pancreatic cancer(PC) was found to be linked to the METTL3-dependent m6A methylation of the lncRNA. Mechanistically, lncRNA DBH-AS1 was able to increase PC cell sensitivity to gemcitabine by sequestering miR-3163 and thus upregulating USP44 in these tumor cells."	M6ADIS0061	31015415; 35433957	M6ADRUG0024
M6ACROT02128	REG00007	M6ATAR00285	DNA methylation	EPIREG00027	EPITAR00027	.	Up regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"Quantitative chromatin immunoprecipitation (ChIP) assays showed that CSC substantially reduced the bindings of DNA methyltransferase 1 (DNMT1) and DNMT3A to the METTL3 promoter. METTL3 may post-transcriptionally upregulate DNA-binding protein inhibitor ID-2 (ID2) expression in an m6A-YTHDF2-dependent manner to further promote the stabilization of ID2 mRNA, which may be a new target for pancreatic cancer treatment."	M6ADIS0061	31015415; 37196908	.
M6ACROT02129	REG00007	M6ATAR00919	DNA methylation	EPIREG00027	EPITAR00027	.	Down regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	Quantitative chromatin immunoprecipitation (ChIP) assays showed that CSC substantially reduced the bindings of DNA methyltransferase 1 (DNMT1) and DNMT3A to the METTL3 promoter. This study demonstrates the promise of BRAF-activated non-protein coding RNA (BANCR) as a new diagnostic and therapeutic target for pancreatic cancer and reveals the therapeutic effect that STM2457(METTL3) exerts on pancreatic cancer by down-regulating BANCR m6A modifications.	M6ADIS0061	31015415; 37998732	.
M6ACROT02130	REG00007	M6ATAR00944	DNA methylation	EPIREG00027	EPITAR00027	.	Up regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"Quantitative chromatin immunoprecipitation (ChIP) assays showed that CSC substantially reduced the bindings of DNA methyltransferase 1 (DNMT1) and DNMT3A to the METTL3 promoter. METTL3 was upregulated in PC tissues and cells and was associated with malignant tumor progression and poor progression-free survival in PC.Four m6A motifs were identified in Long intergenic non-protein coding RNA 662 (LINC00662), which maintained the stability of Linc00662 in an IGF2BP3-coupled manner and were closely associated with the pro-tumor properties of Linc00662 in vitro and in vivo."	M6ADIS0061	31015415; 37293163	.
M6ACROT02131	REG00007	M6ATAR00967	DNA methylation	EPIREG00027	EPITAR00027	.	Up regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"Quantitative chromatin immunoprecipitation (ChIP) assays showed that CSC substantially reduced the bindings of DNA methyltransferase 1 (DNMT1) and DNMT3A to the METTL3 promoter. celastrol treatment downregulated METTL3 and decreased m6A levels of Claspin (CLSPN) and Bcl-2 mRNA, leading to the degradation of Claspin and Bcl-2 mRNA in pancreatic cancer cells. Furthermore, we revealed that celastrol treatment downregulated Claspin and Bcl-2, at least in part, in an m6A-YTHDF3-mediated manner in pancreatic cancer cells."	M6ADIS0061	31015415; 38110764	M6ADRUG0176
M6ACROT02132	REG00007	M6ATAR00196	DNA methylation	EPIREG00027	EPITAR00027	.	Up regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"Quantitative chromatin immunoprecipitation (ChIP) assays showed that CSC substantially reduced the bindings of DNA methyltransferase 1 (DNMT1) and DNMT3A to the METTL3 promoter. celastrol treatment downregulated METTL3 and decreased m6A levels of Claspin and Apoptosis regulator Bcl-2 (BCL2) mRNA, leading to the degradation of Claspin and Bcl-2 mRNA in pancreatic cancer cells. Furthermore, we revealed that celastrol treatment downregulated Claspin and Bcl-2, at least in part, in an m6A-YTHDF3-mediated manner in pancreatic cancer cells."	M6ADIS0061	31015415; 38110764	M6ADRUG0176
M6ACROT02133	REG00007	M6ATAR00298	DNA methylation	EPIREG00027	EPITAR00027	.	.	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	Quantitative chromatin immunoprecipitation (ChIP) assays showed that CSC substantially reduced the bindings of DNA methyltransferase 1 (DNMT1) and DNMT3A to the METTL3 promoter. Hypoxia promotes immune escape of pancreatic cancer cells by lncRNA NNT-AS1/METTL3-HuR-mediated Integrin beta-1 (ITGB1) m6A modification	M6ADIS0061	31015415; 37659467	.
M6ACROT02134	REG00005	M6ATAR00258	DNA methylation	EPIREG00028	EPITAR00183	.	Up regulation	DNA methylation	Direct	Enhancement	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"Loss of LKB1 promotes ALKBH5 transcription by DNMT1-mediated DNA methylation mechanism, reduces m6A modification, and increases the stability of m6A target oncogenes, thus contributing to aggressive phenotypes of KRAS-mutated lung cancer.m6A demethylase ALKBH5 affects the proliferation and invasion of lung adenocarcinoma cells under IH by downregulating m6A modification on Forkhead box protein M1 (FOXM1) mRNA and by promoting FOXM1 expression.high FOXM1 expression was associated with cisplatin-based chemotherapy resistance and poor prognosis"	M6ADIS0007	34016959; 31677788	.
M6ACROT02135	REG00005	M6ATAR00420	DNA methylation	EPIREG00028	EPITAR00183	.	Down regulation	DNA methylation	Direct	Enhancement	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"Loss of Serine/threonine-protein kinase STK11 (STK11/LKB1) promotes ALKBH5 transcription by DNMT1-mediated DNA methylation mechanism, reduces m6A modification, and increases the stability of m6A target oncogenes, thus contributing to aggressive phenotypes of KRAS-mutated lung cancer.ALKBH5 gain- or loss-of function could effectively reverse LKB1 regulated cell proliferation, colony formation, and migration of KRAS-mutated lung cancer cells."	M6ADIS0007	34016959; 34016959	.
M6ACROT02136	REG00008	M6ATAR00160	DNA methylation	EPIREG00028	EPITAR00183	.	Up regulation	DNA methylation	Indirect	Inhibition	m6A	DNA methylation indirectly regulates m6A modification through downstream signaling pathways	"Loss of LKB1 promotes RNA demethylase ALKBH5 (ALKBH5) transcription by DNMT1-mediated DNA methylation mechanism, reduces m6A modification, and increases the stability of m6A target oncogenes, thus contributing to aggressive phenotypes of KRAS-mutated lung cancer. YTHDF2 directly binds to the m6A modification site of 6-phosphogluconate dehydrogenase, decarboxylating (6PGD/PGD) three prime untranslated region (3'-UTR) to promote 6PGD mRNA translation in lung cancer cells."	M6ADIS0007	34016959; 31504235	.
M6ACROT02137	REG00008	M6ATAR00531	DNA methylation	EPIREG00028	EPITAR00183	.	Down regulation	DNA methylation	Indirect	Inhibition	m6A	DNA methylation indirectly regulates m6A modification through downstream signaling pathways	"Loss of LKB1 promotes RNA demethylase ALKBH5 (ALKBH5) transcription by DNMT1-mediated DNA methylation mechanism, reduces m6A modification, and increases the stability of m6A target oncogenes, thus contributing to aggressive phenotypes of KRAS-mutated lung cancer. YTHDF2 inhibits the migration and invasion of lung adenocarcinoma cells by regulating the Protein FAM83D (FAM83D)-TGFbeta1-pSMAD2/3 pathway, which will play an important role in lung cancer metastasis."	M6ADIS0007	34016959; 35186724	.
M6ACROT02138	REG00008	M6ATAR00488	DNA methylation	EPIREG00028	EPITAR00183	.	Down regulation	DNA methylation	Indirect	Inhibition	m6A	DNA methylation indirectly regulates m6A modification through downstream signaling pathways	"Loss of LKB1 promotes RNA demethylase ALKBH5 (ALKBH5) transcription by DNMT1-mediated DNA methylation mechanism, reduces m6A modification, and increases the stability of m6A target oncogenes, thus contributing to aggressive phenotypes of KRAS-mutated lung cancer. YTHDF2 inhibits the migration and invasion of lung adenocarcinoma cells by regulating the FAM83D-Transforming growth factor beta-1 proprotein (TGFB1)-pSMAD2/3 pathway, which will play an important role in lung cancer metastasis."	M6ADIS0007	34016959; 35186724	.
M6ACROT02139	REG00008	M6ATAR00532	DNA methylation	EPIREG00028	EPITAR00183	.	Down regulation	DNA methylation	Indirect	Inhibition	m6A	DNA methylation indirectly regulates m6A modification through downstream signaling pathways	"Loss of LKB1 promotes RNA demethylase ALKBH5 (ALKBH5) transcription by DNMT1-mediated DNA methylation mechanism, reduces m6A modification, and increases the stability of m6A target oncogenes, thus contributing to aggressive phenotypes of KRAS-mutated lung cancer. YTHDF2 inhibits the migration and invasion of lung adenocarcinoma cells by regulating the FAM83D-TGFbeta1-Mothers against decapentaplegic homolog 2 (SMAD2) pathway, which will play an important role in lung cancer metastasis."	M6ADIS0007	34016959; 35186724	.
M6ACROT02140	REG00008	M6ATAR00396	DNA methylation	EPIREG00028	EPITAR00183	.	Down regulation	DNA methylation	Indirect	Inhibition	m6A	DNA methylation indirectly regulates m6A modification through downstream signaling pathways	"Loss of LKB1 promotes RNA demethylase ALKBH5 (ALKBH5) transcription by DNMT1-mediated DNA methylation mechanism, reduces m6A modification, and increases the stability of m6A target oncogenes, thus contributing to aggressive phenotypes of KRAS-mutated lung cancer. YTHDF2 inhibits the migration and invasion of lung adenocarcinoma cells by regulating the FAM83D-TGFbeta1-Mothers against decapentaplegic homolog 3 (SMAD3) pathway, which will play an important role in lung cancer metastasis."	M6ADIS0007	34016959; 35186724	.
M6ACROT02141	REG00007	M6ATAR00368	DNA methylation	EPIREG00027	EPITAR00027	.	Up regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"Methyltransferase-like 3 (METTL3) increased the pri-Let-7b, decreased both the pre-Let-7b and mature Let-7b, attenuating the Let-7b controlling of stem cell renewal. The addition of Metformin increased the bindings of DNA methyltransferase-3a/b (DNMT3A/DNMT3B) to the METTL3 promoter. With the help of the readers of NKAP and HNRNPA2B1, the cluster mediated m6A formation on pri-Let-7b processing increased the mature Let-7b, the key player in suppressing Notch signaling and re-captivating Osimertinib treatment. 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	35070958; 30774445	M6ADRUG0007
M6ACROT02142	REG00007	M6ATAR00017	DNA methylation	EPIREG00027	EPITAR00027	.	Down regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"Methyltransferase-like 3 (METTL3) increased the pri-Let-7b, decreased both the pre-Let-7b and mature Let-7b, attenuating the Let-7b controlling of stem cell renewal. The addition of Metformin increased the bindings of DNA methyltransferase-3a/b (DNMT3A/DNMT3B) to the METTL3 promoter. With the help of the readers of NKAP and HNRNPA2B1, the cluster mediated m6A formation on pri-Let-7b processing increased the mature Let-7b, the key player in suppressing Notch signaling and re-captivating Osimertinib treatment. 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	35070958; 31823788	M6ADRUG0007
M6ACROT02143	REG00007	M6ATAR00302	DNA methylation	EPIREG00027	EPITAR00027	.	Up regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"Methyltransferase-like 3 (METTL3) increased the pri-Let-7b, decreased both the pre-Let-7b and mature Let-7b, attenuating the Let-7b controlling of stem cell renewal. The addition of Metformin increased the bindings of DNA methyltransferase-3a/b (DNMT3A/DNMT3B) to the METTL3 promoter. With the help of the readers of NKAP and HNRNPA2B1, the cluster mediated m6A formation on pri-Let-7b processing increased the mature Let-7b, the key player in suppressing Notch signaling and re-captivating Osimertinib treatment. m6A methyltransferase METTL3 is indispensable for TGF-beta-induced EMT of lung cancer cells through the regulation of Transcription factor JunB (JUNB)."	M6ADIS0007	35070958; 31982139	M6ADRUG0007
M6ACROT02145	REG00007	M6ATAR00249	DNA methylation	EPIREG00027	EPITAR00027	.	Up regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"Methyltransferase-like 3 (METTL3) increased the pri-Let-7b, decreased both the pre-Let-7b and mature Let-7b, attenuating the Let-7b controlling of stem cell renewal. The addition of Metformin increased the bindings of DNA methyltransferase-3a/b (DNMT3A/DNMT3B) to the METTL3 promoter. With the help of the readers of NKAP and HNRNPA2B1, the cluster mediated m6A formation on pri-Let-7b processing increased the mature Let-7b, the key player in suppressing Notch signaling and re-captivating Osimertinib treatment. 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	35070958; 32373962	M6ADRUG0007
M6ACROT02146	REG00007	M6ATAR00325	DNA methylation	EPIREG00027	EPITAR00027	.	Up regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"Methyltransferase-like 3 (METTL3) increased the pri-Let-7b, decreased both the pre-Let-7b and mature Let-7b, attenuating the Let-7b controlling of stem cell renewal. The addition of Metformin increased the bindings of DNA methyltransferase-3a/b (DNMT3A/DNMT3B) to the METTL3 promoter. With the help of the readers of NKAP and HNRNPA2B1, the cluster mediated m6A formation on pri-Let-7b processing increased the mature Let-7b, the key player in suppressing Notch signaling and re-captivating Osimertinib treatment. 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	35070958; 33491264	M6ADRUG0007
M6ACROT02147	REG00007	M6ATAR00553	DNA methylation	EPIREG00027	EPITAR00027	.	Down regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"Methyltransferase-like 3 (METTL3) increased the pri-Let-7b, decreased both the pre-Let-7b and mature Let-7b, attenuating the Let-7b controlling of stem cell renewal. The addition of Metformin increased the bindings of DNA methyltransferase-3a/b (DNMT3A/DNMT3B) to the METTL3 promoter. With the help of the readers of NKAP and HNRNPA2B1, the cluster mediated m6A formation on pri-Let-7b processing increased the mature Let-7b, the key player in suppressing Notch signaling and re-captivating Osimertinib treatment. 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	35070958; 33510938	M6ADRUG0007
M6ACROT02148	REG00007	M6ATAR00375	DNA methylation	EPIREG00027	EPITAR00027	.	Down regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"Methyltransferase-like 3 (METTL3) increased the pri-Let-7b, decreased both the pre-Let-7b and mature Let-7b, attenuating the Let-7b controlling of stem cell renewal. The addition of Metformin increased the bindings of DNA methyltransferase-3a/b (DNMT3A/DNMT3B) to the METTL3 promoter. With the help of the readers of NKAP and HNRNPA2B1, the cluster mediated m6A formation on pri-Let-7b processing increased the mature Let-7b, the key player in suppressing Notch signaling and re-captivating Osimertinib treatment. 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	35070958; 35069732	M6ADRUG0007
M6ACROT02149	REG00007	M6ATAR00368	DNA methylation	EPIREG00027	EPITAR00027	.	Up regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"Methyltransferase-like 3 (METTL3) increased the pri-Let-7b, decreased both the pre-Let-7b and mature Let-7b, attenuating the Let-7b controlling of stem cell renewal. The addition of Metformin increased the bindings of DNA methyltransferase-3a/b (DNMT3A/DNMT3B) to the METTL3 promoter. With the help of the readers of NKAP and HNRNPA2B1, the cluster mediated m6A formation on pri-Let-7b processing increased the mature Let-7b, the key player in suppressing Notch signaling and re-captivating Osimertinib treatment. METTL3-mediated m6A methylation promotes lung cancer progression via activating PI3-kinase subunit alpha (PI3k/PIK3CA)/AKT/mTOR pathway."	M6ADIS0007	35070958; 35434840	M6ADRUG0007
M6ACROT02150	REG00007	M6ATAR00175	DNA methylation	EPIREG00027	EPITAR00027	.	Up regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"Methyltransferase-like 3 (METTL3) increased the pri-Let-7b, decreased both the pre-Let-7b and mature Let-7b, attenuating the Let-7b controlling of stem cell renewal. The addition of Metformin increased the bindings of DNA methyltransferase-3a/b (DNMT3A/DNMT3B) to the METTL3 promoter. With the help of the readers of NKAP and HNRNPA2B1, the cluster mediated m6A formation on pri-Let-7b processing increased the mature Let-7b, the key player in suppressing Notch signaling and re-captivating Osimertinib treatment. METTL3-mediated m6A methylation promotes lung cancer progression via activating PI3K/RAC-alpha serine/threonine-protein kinase (AKT1)/mTOR pathway."	M6ADIS0007	35070958; 35434840	M6ADRUG0007
M6ACROT02151	REG00007	M6ATAR00339	DNA methylation	EPIREG00027	EPITAR00027	.	Up regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"Methyltransferase-like 3 (METTL3) increased the pri-Let-7b, decreased both the pre-Let-7b and mature Let-7b, attenuating the Let-7b controlling of stem cell renewal. The addition of Metformin increased the bindings of DNA methyltransferase-3a/b (DNMT3A/DNMT3B) to the METTL3 promoter. With the help of the readers of NKAP and HNRNPA2B1, the cluster mediated m6A formation on pri-Let-7b processing increased the mature Let-7b, the key player in suppressing Notch signaling and re-captivating Osimertinib treatment. METTL3-mediated m6A methylation promotes lung cancer progression via activating PI3K/AKT/Serine/threonine-protein kinase mTOR (MTOR) pathway."	M6ADIS0007	35070958; 35434840	M6ADRUG0007
M6ACROT02152	REG00007	M6ATAR00673	DNA methylation	EPIREG00027	EPITAR00027	.	Up regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"Methyltransferase-like 3 (METTL3) increased the pri-Let-7b, decreased both the pre-Let-7b and mature Let-7b, attenuating the Let-7b controlling of stem cell renewal. The addition of Metformin increased the bindings of DNA methyltransferase-3a/b (DNMT3A/DNMT3B) to the METTL3 promoter. With the help of the readers of NKAP and HNRNPA2B1, the cluster mediated m6A formation on pri-Let-7b processing increased the mature Let-7b, the key player in suppressing Notch signaling and re-captivating Osimertinib treatment. 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	35070958; 35068325	M6ADRUG0007
M6ACROT02153	REG00007	M6ATAR00890	DNA methylation	EPIREG00027	EPITAR00027	.	Up regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"Methyltransferase-like 3 (METTL3) increased the pri-Let-7b, decreased both the pre-Let-7b and mature Let-7b, attenuating the Let-7b controlling of stem cell renewal. The addition of Metformin increased the bindings of DNA methyltransferase-3a/b (DNMT3A/DNMT3B) to the METTL3 promoter. With the help of the readers of NKAP and HNRNPA2B1, the cluster mediated m6A formation on pri-Let-7b processing increased the mature Let-7b, the key player in suppressing Notch signaling and re-captivating Osimertinib treatment. 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	35070958; 38141906	M6ADRUG0007
M6ACROT02154	REG00007	M6ATAR00368	DNA methylation	EPIREG00029	EPITAR00027	.	Up regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"Methyltransferase-like 3 (METTL3) increased the pri-Let-7b, decreased both the pre-Let-7b and mature Let-7b, attenuating the Let-7b controlling of stem cell renewal. The addition of Metformin increased the bindings of DNA methyltransferase-3a/b (DNMT3A/DNMT3B) to the METTL3 promoter. With the help of the readers of NKAP and HNRNPA2B1, the cluster mediated m6A formation on pri-Let-7b processing increased the mature Let-7b, the key player in suppressing Notch signaling and re-captivating Osimertinib treatment. 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	35070958; 30774445	M6ADRUG0007
M6ACROT02155	REG00007	M6ATAR00017	DNA methylation	EPIREG00029	EPITAR00027	.	Down regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"Methyltransferase-like 3 (METTL3) increased the pri-Let-7b, decreased both the pre-Let-7b and mature Let-7b, attenuating the Let-7b controlling of stem cell renewal. The addition of Metformin increased the bindings of DNA methyltransferase-3a/b (DNMT3A/DNMT3B) to the METTL3 promoter. With the help of the readers of NKAP and HNRNPA2B1, the cluster mediated m6A formation on pri-Let-7b processing increased the mature Let-7b, the key player in suppressing Notch signaling and re-captivating Osimertinib treatment. 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	35070958; 31823788	M6ADRUG0007
M6ACROT02156	REG00007	M6ATAR00302	DNA methylation	EPIREG00029	EPITAR00027	.	Up regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"Methyltransferase-like 3 (METTL3) increased the pri-Let-7b, decreased both the pre-Let-7b and mature Let-7b, attenuating the Let-7b controlling of stem cell renewal. The addition of Metformin increased the bindings of DNA methyltransferase-3a/b (DNMT3A/DNMT3B) to the METTL3 promoter. With the help of the readers of NKAP and HNRNPA2B1, the cluster mediated m6A formation on pri-Let-7b processing increased the mature Let-7b, the key player in suppressing Notch signaling and re-captivating Osimertinib treatment. m6A methyltransferase METTL3 is indispensable for TGF-beta-induced EMT of lung cancer cells through the regulation of Transcription factor JunB (JUNB)."	M6ADIS0007	35070958; 31982139	M6ADRUG0007
M6ACROT02158	REG00007	M6ATAR00249	DNA methylation	EPIREG00029	EPITAR00027	.	Up regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"Methyltransferase-like 3 (METTL3) increased the pri-Let-7b, decreased both the pre-Let-7b and mature Let-7b, attenuating the Let-7b controlling of stem cell renewal. The addition of Metformin increased the bindings of DNA methyltransferase-3a/b (DNMT3A/DNMT3B) to the METTL3 promoter. With the help of the readers of NKAP and HNRNPA2B1, the cluster mediated m6A formation on pri-Let-7b processing increased the mature Let-7b, the key player in suppressing Notch signaling and re-captivating Osimertinib treatment. 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	35070958; 32373962	M6ADRUG0007
M6ACROT02159	REG00007	M6ATAR00325	DNA methylation	EPIREG00029	EPITAR00027	.	Up regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"Methyltransferase-like 3 (METTL3) increased the pri-Let-7b, decreased both the pre-Let-7b and mature Let-7b, attenuating the Let-7b controlling of stem cell renewal. The addition of Metformin increased the bindings of DNA methyltransferase-3a/b (DNMT3A/DNMT3B) to the METTL3 promoter. With the help of the readers of NKAP and HNRNPA2B1, the cluster mediated m6A formation on pri-Let-7b processing increased the mature Let-7b, the key player in suppressing Notch signaling and re-captivating Osimertinib treatment. 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	35070958; 33491264	M6ADRUG0007
M6ACROT02160	REG00007	M6ATAR00553	DNA methylation	EPIREG00029	EPITAR00027	.	Down regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"Methyltransferase-like 3 (METTL3) increased the pri-Let-7b, decreased both the pre-Let-7b and mature Let-7b, attenuating the Let-7b controlling of stem cell renewal. The addition of Metformin increased the bindings of DNA methyltransferase-3a/b (DNMT3A/DNMT3B) to the METTL3 promoter. With the help of the readers of NKAP and HNRNPA2B1, the cluster mediated m6A formation on pri-Let-7b processing increased the mature Let-7b, the key player in suppressing Notch signaling and re-captivating Osimertinib treatment. 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	35070958; 33510938	M6ADRUG0007
M6ACROT02161	REG00007	M6ATAR00375	DNA methylation	EPIREG00029	EPITAR00027	.	Down regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"Methyltransferase-like 3 (METTL3) increased the pri-Let-7b, decreased both the pre-Let-7b and mature Let-7b, attenuating the Let-7b controlling of stem cell renewal. The addition of Metformin increased the bindings of DNA methyltransferase-3a/b (DNMT3A/DNMT3B) to the METTL3 promoter. With the help of the readers of NKAP and HNRNPA2B1, the cluster mediated m6A formation on pri-Let-7b processing increased the mature Let-7b, the key player in suppressing Notch signaling and re-captivating Osimertinib treatment. 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	35070958; 35069732	M6ADRUG0007
M6ACROT02162	REG00007	M6ATAR00368	DNA methylation	EPIREG00029	EPITAR00027	.	Up regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"Methyltransferase-like 3 (METTL3) increased the pri-Let-7b, decreased both the pre-Let-7b and mature Let-7b, attenuating the Let-7b controlling of stem cell renewal. The addition of Metformin increased the bindings of DNA methyltransferase-3a/b (DNMT3A/DNMT3B) to the METTL3 promoter. With the help of the readers of NKAP and HNRNPA2B1, the cluster mediated m6A formation on pri-Let-7b processing increased the mature Let-7b, the key player in suppressing Notch signaling and re-captivating Osimertinib treatment. METTL3-mediated m6A methylation promotes lung cancer progression via activating PI3-kinase subunit alpha (PI3k/PIK3CA)/AKT/mTOR pathway."	M6ADIS0007	35070958; 35434840	M6ADRUG0007
M6ACROT02163	REG00007	M6ATAR00175	DNA methylation	EPIREG00029	EPITAR00027	.	Up regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"Methyltransferase-like 3 (METTL3) increased the pri-Let-7b, decreased both the pre-Let-7b and mature Let-7b, attenuating the Let-7b controlling of stem cell renewal. The addition of Metformin increased the bindings of DNA methyltransferase-3a/b (DNMT3A/DNMT3B) to the METTL3 promoter. With the help of the readers of NKAP and HNRNPA2B1, the cluster mediated m6A formation on pri-Let-7b processing increased the mature Let-7b, the key player in suppressing Notch signaling and re-captivating Osimertinib treatment. METTL3-mediated m6A methylation promotes lung cancer progression via activating PI3K/RAC-alpha serine/threonine-protein kinase (AKT1)/mTOR pathway."	M6ADIS0007	35070958; 35434840	M6ADRUG0007
M6ACROT02164	REG00007	M6ATAR00339	DNA methylation	EPIREG00029	EPITAR00027	.	Up regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"Methyltransferase-like 3 (METTL3) increased the pri-Let-7b, decreased both the pre-Let-7b and mature Let-7b, attenuating the Let-7b controlling of stem cell renewal. The addition of Metformin increased the bindings of DNA methyltransferase-3a/b (DNMT3A/DNMT3B) to the METTL3 promoter. With the help of the readers of NKAP and HNRNPA2B1, the cluster mediated m6A formation on pri-Let-7b processing increased the mature Let-7b, the key player in suppressing Notch signaling and re-captivating Osimertinib treatment. METTL3-mediated m6A methylation promotes lung cancer progression via activating PI3K/AKT/Serine/threonine-protein kinase mTOR (MTOR) pathway."	M6ADIS0007	35070958; 35434840	M6ADRUG0007
M6ACROT02165	REG00007	M6ATAR00673	DNA methylation	EPIREG00029	EPITAR00027	.	Up regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"Methyltransferase-like 3 (METTL3) increased the pri-Let-7b, decreased both the pre-Let-7b and mature Let-7b, attenuating the Let-7b controlling of stem cell renewal. The addition of Metformin increased the bindings of DNA methyltransferase-3a/b (DNMT3A/DNMT3B) to the METTL3 promoter. With the help of the readers of NKAP and HNRNPA2B1, the cluster mediated m6A formation on pri-Let-7b processing increased the mature Let-7b, the key player in suppressing Notch signaling and re-captivating Osimertinib treatment. 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	35070958; 35068325	M6ADRUG0007
M6ACROT02166	REG00007	M6ATAR00890	DNA methylation	EPIREG00029	EPITAR00027	.	Up regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"Methyltransferase-like 3 (METTL3) increased the pri-Let-7b, decreased both the pre-Let-7b and mature Let-7b, attenuating the Let-7b controlling of stem cell renewal. The addition of Metformin increased the bindings of DNA methyltransferase-3a/b (DNMT3A/DNMT3B) to the METTL3 promoter. With the help of the readers of NKAP and HNRNPA2B1, the cluster mediated m6A formation on pri-Let-7b processing increased the mature Let-7b, the key player in suppressing Notch signaling and re-captivating Osimertinib treatment. 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	35070958; 38141906	M6ADRUG0007
M6ACROT02167	REG00007	M6ATAR00368	DNA methylation	EPIREG00027	EPITAR00027	.	Up regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"Methyltransferase-like 3 (METTL3) increased the pri-Let-7b, decreased both the pre-Let-7b and mature Let-7b, attenuating the Let-7b controlling of stem cell renewal. The addition of Metformin increased the bindings of DNA methyltransferase-3a/b (DNMT3A/DNMT3B) to the METTL3 promoter. With the help of the readers of NKAP and HNRNPA2B1, the cluster mediated m6A formation on pri-Let-7b processing increased the mature Let-7b, the key player in suppressing Notch signaling and re-captivating Osimertinib treatment. 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	35070958; 30774445	M6ADRUG0090
M6ACROT02168	REG00007	M6ATAR00017	DNA methylation	EPIREG00027	EPITAR00027	.	Down regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"Methyltransferase-like 3 (METTL3) increased the pri-Let-7b, decreased both the pre-Let-7b and mature Let-7b, attenuating the Let-7b controlling of stem cell renewal. The addition of Metformin increased the bindings of DNA methyltransferase-3a/b (DNMT3A/DNMT3B) to the METTL3 promoter. With the help of the readers of NKAP and HNRNPA2B1, the cluster mediated m6A formation on pri-Let-7b processing increased the mature Let-7b, the key player in suppressing Notch signaling and re-captivating Osimertinib treatment. 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	35070958; 31823788	M6ADRUG0090
M6ACROT02169	REG00007	M6ATAR00302	DNA methylation	EPIREG00027	EPITAR00027	.	Up regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"Methyltransferase-like 3 (METTL3) increased the pri-Let-7b, decreased both the pre-Let-7b and mature Let-7b, attenuating the Let-7b controlling of stem cell renewal. The addition of Metformin increased the bindings of DNA methyltransferase-3a/b (DNMT3A/DNMT3B) to the METTL3 promoter. With the help of the readers of NKAP and HNRNPA2B1, the cluster mediated m6A formation on pri-Let-7b processing increased the mature Let-7b, the key player in suppressing Notch signaling and re-captivating Osimertinib treatment. m6A methyltransferase METTL3 is indispensable for TGF-beta-induced EMT of lung cancer cells through the regulation of Transcription factor JunB (JUNB)."	M6ADIS0007	35070958; 31982139	M6ADRUG0090
M6ACROT02171	REG00007	M6ATAR00249	DNA methylation	EPIREG00027	EPITAR00027	.	Up regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"Methyltransferase-like 3 (METTL3) increased the pri-Let-7b, decreased both the pre-Let-7b and mature Let-7b, attenuating the Let-7b controlling of stem cell renewal. The addition of Metformin increased the bindings of DNA methyltransferase-3a/b (DNMT3A/DNMT3B) to the METTL3 promoter. With the help of the readers of NKAP and HNRNPA2B1, the cluster mediated m6A formation on pri-Let-7b processing increased the mature Let-7b, the key player in suppressing Notch signaling and re-captivating Osimertinib treatment. 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	35070958; 32373962	M6ADRUG0090
M6ACROT02172	REG00007	M6ATAR00325	DNA methylation	EPIREG00027	EPITAR00027	.	Up regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"Methyltransferase-like 3 (METTL3) increased the pri-Let-7b, decreased both the pre-Let-7b and mature Let-7b, attenuating the Let-7b controlling of stem cell renewal. The addition of Metformin increased the bindings of DNA methyltransferase-3a/b (DNMT3A/DNMT3B) to the METTL3 promoter. With the help of the readers of NKAP and HNRNPA2B1, the cluster mediated m6A formation on pri-Let-7b processing increased the mature Let-7b, the key player in suppressing Notch signaling and re-captivating Osimertinib treatment. 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	35070958; 33491264	M6ADRUG0090
M6ACROT02173	REG00007	M6ATAR00553	DNA methylation	EPIREG00027	EPITAR00027	.	Down regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"Methyltransferase-like 3 (METTL3) increased the pri-Let-7b, decreased both the pre-Let-7b and mature Let-7b, attenuating the Let-7b controlling of stem cell renewal. The addition of Metformin increased the bindings of DNA methyltransferase-3a/b (DNMT3A/DNMT3B) to the METTL3 promoter. With the help of the readers of NKAP and HNRNPA2B1, the cluster mediated m6A formation on pri-Let-7b processing increased the mature Let-7b, the key player in suppressing Notch signaling and re-captivating Osimertinib treatment. 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	35070958; 33510938	M6ADRUG0090
M6ACROT02174	REG00007	M6ATAR00375	DNA methylation	EPIREG00027	EPITAR00027	.	Down regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"Methyltransferase-like 3 (METTL3) increased the pri-Let-7b, decreased both the pre-Let-7b and mature Let-7b, attenuating the Let-7b controlling of stem cell renewal. The addition of Metformin increased the bindings of DNA methyltransferase-3a/b (DNMT3A/DNMT3B) to the METTL3 promoter. With the help of the readers of NKAP and HNRNPA2B1, the cluster mediated m6A formation on pri-Let-7b processing increased the mature Let-7b, the key player in suppressing Notch signaling and re-captivating Osimertinib treatment. 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	35070958; 35069732	M6ADRUG0090
M6ACROT02175	REG00007	M6ATAR00368	DNA methylation	EPIREG00027	EPITAR00027	.	Up regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"Methyltransferase-like 3 (METTL3) increased the pri-Let-7b, decreased both the pre-Let-7b and mature Let-7b, attenuating the Let-7b controlling of stem cell renewal. The addition of Metformin increased the bindings of DNA methyltransferase-3a/b (DNMT3A/DNMT3B) to the METTL3 promoter. With the help of the readers of NKAP and HNRNPA2B1, the cluster mediated m6A formation on pri-Let-7b processing increased the mature Let-7b, the key player in suppressing Notch signaling and re-captivating Osimertinib treatment. METTL3-mediated m6A methylation promotes lung cancer progression via activating PI3-kinase subunit alpha (PI3k/PIK3CA)/AKT/mTOR pathway."	M6ADIS0007	35070958; 35434840	M6ADRUG0090
M6ACROT02176	REG00007	M6ATAR00175	DNA methylation	EPIREG00027	EPITAR00027	.	Up regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"Methyltransferase-like 3 (METTL3) increased the pri-Let-7b, decreased both the pre-Let-7b and mature Let-7b, attenuating the Let-7b controlling of stem cell renewal. The addition of Metformin increased the bindings of DNA methyltransferase-3a/b (DNMT3A/DNMT3B) to the METTL3 promoter. With the help of the readers of NKAP and HNRNPA2B1, the cluster mediated m6A formation on pri-Let-7b processing increased the mature Let-7b, the key player in suppressing Notch signaling and re-captivating Osimertinib treatment. METTL3-mediated m6A methylation promotes lung cancer progression via activating PI3K/RAC-alpha serine/threonine-protein kinase (AKT1)/mTOR pathway."	M6ADIS0007	35070958; 35434840	M6ADRUG0090
M6ACROT02177	REG00007	M6ATAR00339	DNA methylation	EPIREG00027	EPITAR00027	.	Up regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"Methyltransferase-like 3 (METTL3) increased the pri-Let-7b, decreased both the pre-Let-7b and mature Let-7b, attenuating the Let-7b controlling of stem cell renewal. The addition of Metformin increased the bindings of DNA methyltransferase-3a/b (DNMT3A/DNMT3B) to the METTL3 promoter. With the help of the readers of NKAP and HNRNPA2B1, the cluster mediated m6A formation on pri-Let-7b processing increased the mature Let-7b, the key player in suppressing Notch signaling and re-captivating Osimertinib treatment. METTL3-mediated m6A methylation promotes lung cancer progression via activating PI3K/AKT/Serine/threonine-protein kinase mTOR (MTOR) pathway."	M6ADIS0007	35070958; 35434840	M6ADRUG0090
M6ACROT02178	REG00007	M6ATAR00673	DNA methylation	EPIREG00027	EPITAR00027	.	Up regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"Methyltransferase-like 3 (METTL3) increased the pri-Let-7b, decreased both the pre-Let-7b and mature Let-7b, attenuating the Let-7b controlling of stem cell renewal. The addition of Metformin increased the bindings of DNA methyltransferase-3a/b (DNMT3A/DNMT3B) to the METTL3 promoter. With the help of the readers of NKAP and HNRNPA2B1, the cluster mediated m6A formation on pri-Let-7b processing increased the mature Let-7b, the key player in suppressing Notch signaling and re-captivating Osimertinib treatment. 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	35070958; 35068325	M6ADRUG0090
M6ACROT02179	REG00007	M6ATAR00890	DNA methylation	EPIREG00027	EPITAR00027	.	Up regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"Methyltransferase-like 3 (METTL3) increased the pri-Let-7b, decreased both the pre-Let-7b and mature Let-7b, attenuating the Let-7b controlling of stem cell renewal. The addition of Metformin increased the bindings of DNA methyltransferase-3a/b (DNMT3A/DNMT3B) to the METTL3 promoter. With the help of the readers of NKAP and HNRNPA2B1, the cluster mediated m6A formation on pri-Let-7b processing increased the mature Let-7b, the key player in suppressing Notch signaling and re-captivating Osimertinib treatment. 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	35070958; 38141906	M6ADRUG0090
M6ACROT02180	REG00007	M6ATAR00368	DNA methylation	EPIREG00029	EPITAR00027	.	Up regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"Methyltransferase-like 3 (METTL3) increased the pri-Let-7b, decreased both the pre-Let-7b and mature Let-7b, attenuating the Let-7b controlling of stem cell renewal. The addition of Metformin increased the bindings of DNA methyltransferase-3a/b (DNMT3A/DNMT3B) to the METTL3 promoter. With the help of the readers of NKAP and HNRNPA2B1, the cluster mediated m6A formation on pri-Let-7b processing increased the mature Let-7b, the key player in suppressing Notch signaling and re-captivating Osimertinib treatment. 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	35070958; 30774445	M6ADRUG0090
M6ACROT02181	REG00007	M6ATAR00017	DNA methylation	EPIREG00029	EPITAR00027	.	Down regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"Methyltransferase-like 3 (METTL3) increased the pri-Let-7b, decreased both the pre-Let-7b and mature Let-7b, attenuating the Let-7b controlling of stem cell renewal. The addition of Metformin increased the bindings of DNA methyltransferase-3a/b (DNMT3A/DNMT3B) to the METTL3 promoter. With the help of the readers of NKAP and HNRNPA2B1, the cluster mediated m6A formation on pri-Let-7b processing increased the mature Let-7b, the key player in suppressing Notch signaling and re-captivating Osimertinib treatment. 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	35070958; 31823788	M6ADRUG0090
M6ACROT02182	REG00007	M6ATAR00302	DNA methylation	EPIREG00029	EPITAR00027	.	Up regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"Methyltransferase-like 3 (METTL3) increased the pri-Let-7b, decreased both the pre-Let-7b and mature Let-7b, attenuating the Let-7b controlling of stem cell renewal. The addition of Metformin increased the bindings of DNA methyltransferase-3a/b (DNMT3A/DNMT3B) to the METTL3 promoter. With the help of the readers of NKAP and HNRNPA2B1, the cluster mediated m6A formation on pri-Let-7b processing increased the mature Let-7b, the key player in suppressing Notch signaling and re-captivating Osimertinib treatment. m6A methyltransferase METTL3 is indispensable for TGF-beta-induced EMT of lung cancer cells through the regulation of Transcription factor JunB (JUNB)."	M6ADIS0007	35070958; 31982139	M6ADRUG0090
M6ACROT02184	REG00007	M6ATAR00249	DNA methylation	EPIREG00029	EPITAR00027	.	Up regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"Methyltransferase-like 3 (METTL3) increased the pri-Let-7b, decreased both the pre-Let-7b and mature Let-7b, attenuating the Let-7b controlling of stem cell renewal. The addition of Metformin increased the bindings of DNA methyltransferase-3a/b (DNMT3A/DNMT3B) to the METTL3 promoter. With the help of the readers of NKAP and HNRNPA2B1, the cluster mediated m6A formation on pri-Let-7b processing increased the mature Let-7b, the key player in suppressing Notch signaling and re-captivating Osimertinib treatment. 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	35070958; 32373962	M6ADRUG0090
M6ACROT02185	REG00007	M6ATAR00325	DNA methylation	EPIREG00029	EPITAR00027	.	Up regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"Methyltransferase-like 3 (METTL3) increased the pri-Let-7b, decreased both the pre-Let-7b and mature Let-7b, attenuating the Let-7b controlling of stem cell renewal. The addition of Metformin increased the bindings of DNA methyltransferase-3a/b (DNMT3A/DNMT3B) to the METTL3 promoter. With the help of the readers of NKAP and HNRNPA2B1, the cluster mediated m6A formation on pri-Let-7b processing increased the mature Let-7b, the key player in suppressing Notch signaling and re-captivating Osimertinib treatment. 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	35070958; 33491264	M6ADRUG0090
M6ACROT02186	REG00007	M6ATAR00553	DNA methylation	EPIREG00029	EPITAR00027	.	Down regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"Methyltransferase-like 3 (METTL3) increased the pri-Let-7b, decreased both the pre-Let-7b and mature Let-7b, attenuating the Let-7b controlling of stem cell renewal. The addition of Metformin increased the bindings of DNA methyltransferase-3a/b (DNMT3A/DNMT3B) to the METTL3 promoter. With the help of the readers of NKAP and HNRNPA2B1, the cluster mediated m6A formation on pri-Let-7b processing increased the mature Let-7b, the key player in suppressing Notch signaling and re-captivating Osimertinib treatment. 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	35070958; 33510938	M6ADRUG0090
M6ACROT02187	REG00007	M6ATAR00375	DNA methylation	EPIREG00029	EPITAR00027	.	Down regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"Methyltransferase-like 3 (METTL3) increased the pri-Let-7b, decreased both the pre-Let-7b and mature Let-7b, attenuating the Let-7b controlling of stem cell renewal. The addition of Metformin increased the bindings of DNA methyltransferase-3a/b (DNMT3A/DNMT3B) to the METTL3 promoter. With the help of the readers of NKAP and HNRNPA2B1, the cluster mediated m6A formation on pri-Let-7b processing increased the mature Let-7b, the key player in suppressing Notch signaling and re-captivating Osimertinib treatment. 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	35070958; 35069732	M6ADRUG0090
M6ACROT02188	REG00007	M6ATAR00368	DNA methylation	EPIREG00029	EPITAR00027	.	Up regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"Methyltransferase-like 3 (METTL3) increased the pri-Let-7b, decreased both the pre-Let-7b and mature Let-7b, attenuating the Let-7b controlling of stem cell renewal. The addition of Metformin increased the bindings of DNA methyltransferase-3a/b (DNMT3A/DNMT3B) to the METTL3 promoter. With the help of the readers of NKAP and HNRNPA2B1, the cluster mediated m6A formation on pri-Let-7b processing increased the mature Let-7b, the key player in suppressing Notch signaling and re-captivating Osimertinib treatment. METTL3-mediated m6 A methylation promotes lung cancer progression via activating PI3-kinase subunit alpha (PI3k/PIK3CA)/AKT/mTOR pathway."	M6ADIS0007	35070958; 35434840	M6ADRUG0090
M6ACROT02189	REG00007	M6ATAR00175	DNA methylation	EPIREG00029	EPITAR00027	.	Up regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"Methyltransferase-like 3 (METTL3) increased the pri-Let-7b, decreased both the pre-Let-7b and mature Let-7b, attenuating the Let-7b controlling of stem cell renewal. The addition of Metformin increased the bindings of DNA methyltransferase-3a/b (DNMT3A/DNMT3B) to the METTL3 promoter. With the help of the readers of NKAP and HNRNPA2B1, the cluster mediated m6A formation on pri-Let-7b processing increased the mature Let-7b, the key player in suppressing Notch signaling and re-captivating Osimertinib treatment. METTL3-mediated m6 A methylation promotes lung cancer progression via activating PI3K/RAC-alpha serine/threonine-protein kinase (AKT1)/mTOR pathway."	M6ADIS0007	35070958; 35434840	M6ADRUG0090
M6ACROT02190	REG00007	M6ATAR00339	DNA methylation	EPIREG00029	EPITAR00027	.	Up regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"Methyltransferase-like 3 (METTL3) increased the pri-Let-7b, decreased both the pre-Let-7b and mature Let-7b, attenuating the Let-7b controlling of stem cell renewal. The addition of Metformin increased the bindings of DNA methyltransferase-3a/b (DNMT3A/DNMT3B) to the METTL3 promoter. With the help of the readers of NKAP and HNRNPA2B1, the cluster mediated m6A formation on pri-Let-7b processing increased the mature Let-7b, the key player in suppressing Notch signaling and re-captivating Osimertinib treatment. METTL3-mediated m6 A methylation promotes lung cancer progression via activating PI3K/AKT/Serine/threonine-protein kinase mTOR (MTOR) pathway."	M6ADIS0007	35070958; 35434840	M6ADRUG0090
M6ACROT02191	REG00007	M6ATAR00673	DNA methylation	EPIREG00029	EPITAR00027	.	Up regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"Methyltransferase-like 3 (METTL3) increased the pri-Let-7b, decreased both the pre-Let-7b and mature Let-7b, attenuating the Let-7b controlling of stem cell renewal. The addition of Metformin increased the bindings of DNA methyltransferase-3a/b (DNMT3A/DNMT3B) to the METTL3 promoter. With the help of the readers of NKAP and HNRNPA2B1, the cluster mediated m6A formation on pri-Let-7b processing increased the mature Let-7b, the key player in suppressing Notch signaling and re-captivating Osimertinib treatment. 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	35070958; 35068325	M6ADRUG0090
M6ACROT02192	REG00007	M6ATAR00890	DNA methylation	EPIREG00029	EPITAR00027	.	Up regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"Methyltransferase-like 3 (METTL3) increased the pri-Let-7b, decreased both the pre-Let-7b and mature Let-7b, attenuating the Let-7b controlling of stem cell renewal. The addition of Metformin increased the bindings of DNA methyltransferase-3a/b (DNMT3A/DNMT3B) to the METTL3 promoter. With the help of the readers of NKAP and HNRNPA2B1, the cluster mediated m6A formation on pri-Let-7b processing increased the mature Let-7b, the key player in suppressing Notch signaling and re-captivating Osimertinib treatment. 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	35070958; 38141906	M6ADRUG0090
M6ACROT02193	REG00012	M6ATAR00308	DNA methylation	EPIREG00027	EPITAR00192	.	.	DNA methylation	Indirect	Inhibition	m6A	DNA methylation indirectly regulates m6A modification through downstream signaling pathways	"We identified Protein tyrosine phosphatase non-receptor type 13 (PTPN13) expression by upregulating the expression of DNMT3A and IGF2BP1 as a novel PTPN13-interacting gene and demonstrated that PTPN13 influences c-Myc expression by directly and competitively binding to IGF2BP1 to decrease the intracellular concentration of functional IGF2BP1. Overexpressing PTPN13 promoted c-Myc mRNA degradation independent of the protein tyrosine phosphatase (PTP) activity of PTPN13. Importantly, we discovered that the PTPN13-IGF2BP1-c-Myc axis was important for cancer cell growth through promoting metabolic reprogramming. In contrast to the mRNA-decay-promoting function of YTH domain-containing family protein 2, IGF2BPs promote the stability and storage of their target mRNAs (for example, MYC) in an m6A-dependent manner under normal and stress conditions and therefore affect gene expression output. Four representative high confidence targets, including MYC, FSCN1, Thymidine kinase, cytosolic (TK1), and MARCKSL1, exhibit strong binding with IGF2BPs around their m6A motifs in control cells. Knocking down of each individual IGF2BPs in Hela (cervical cancer) and HepG2 (liver cancer) cells significantly repressed MYC expression."	M6ADIS0006	33051595; 29476152	.
M6ACROT02194	REG00012	M6ATAR00341	DNA methylation	EPIREG00027	EPITAR00192	.	.	DNA methylation	Indirect	Inhibition	m6A	DNA methylation indirectly regulates m6A modification through downstream signaling pathways	"We identified Protein tyrosine phosphatase non-receptor type 13 (PTPN13) expression by upregulating the expression of DNMT3A and IGF2BP1 as a novel PTPN13-interacting gene and demonstrated that PTPN13 influences c-Myc expression by directly and competitively binding to IGF2BP1 to decrease the intracellular concentration of functional IGF2BP1. Overexpressing PTPN13 promoted c-Myc mRNA degradation independent of the protein tyrosine phosphatase (PTP) activity of PTPN13. Importantly, we discovered that the PTPN13-IGF2BP1-c-Myc axis was important for cancer cell growth through promoting metabolic reprogramming. In contrast to the mRNA-decay-promoting function of YTH domain-containing family protein 2, IGF2BPs promote the stability and storage of their target mRNAs (for example, Myc proto-oncogene protein (MYC)) in an m6A-dependent manner under normal and stress conditions and therefore affect gene expression output. Four representative high confidence targets, including MYC, FSCN1, TK1, and MARCKSL1, exhibit strong binding with IGF2BPs around their m6A motifs in control cells. Knocking down of each individual IGF2BPs in Hela (cervical cancer) and HepG2 (liver cancer) cells significantly repressed MYC expression."	M6ADIS0006	33051595; 29476152	.
M6ACROT02195	REG00012	M6ATAR00261	DNA methylation	EPIREG00027	EPITAR00192	.	.	DNA methylation	Indirect	Inhibition	m6A	DNA methylation indirectly regulates m6A modification through downstream signaling pathways	"We identified Protein tyrosine phosphatase non-receptor type 13 (PTPN13) expression by upregulating the expression of DNMT3A and IGF2BP1 as a novel PTPN13-interacting gene and demonstrated that PTPN13 influences c-Myc expression by directly and competitively binding to IGF2BP1 to decrease the intracellular concentration of functional IGF2BP1. Overexpressing PTPN13 promoted c-Myc mRNA degradation independent of the protein tyrosine phosphatase (PTP) activity of PTPN13. Importantly, we discovered that the PTPN13-IGF2BP1-c-Myc axis was important for cancer cell growth through promoting metabolic reprogramming. In contrast to the mRNA-decay-promoting function of YTH domain-containing family protein 2, IGF2BPs promote the stability and storage of their target mRNAs (for example, MYC) in an m6A-dependent manner under normal and stress conditions and therefore affect gene expression output. Four representative high confidence targets, including MYC, Fascin (FSCN1), TK1, and MARCKSL1, exhibit strong binding with IGF2BPs around their m6A motifs in control cells. Knocking down of each individual IGF2BPs in Hela (cervical cancer) and HepG2 (liver cancer) cells significantly repressed MYC expression."	M6ADIS0006	33051595; 29476152	.
M6ACROT02196	REG00012	M6ATAR00337	DNA methylation	EPIREG00027	EPITAR00192	.	.	DNA methylation	Indirect	Inhibition	m6A	DNA methylation indirectly regulates m6A modification through downstream signaling pathways	"We identified Protein tyrosine phosphatase non-receptor type 13 (PTPN13) expression by upregulating the expression of DNMT3A and IGF2BP1 as a novel PTPN13-interacting gene and demonstrated that PTPN13 influences c-Myc expression by directly and competitively binding to IGF2BP1 to decrease the intracellular concentration of functional IGF2BP1. Overexpressing PTPN13 promoted c-Myc mRNA degradation independent of the protein tyrosine phosphatase (PTP) activity of PTPN13. Importantly, we discovered that the PTPN13-IGF2BP1-c-Myc axis was important for cancer cell growth through promoting metabolic reprogramming. In contrast to the mRNA-decay-promoting function of YTH domain-containing family protein 2, IGF2BPs promote the stability and storage of their target mRNAs (for example, MYC) in an m6A-dependent manner under normal and stress conditions and therefore affect gene expression output. Four representative high confidence targets, including MYC, FSCN1, TK1, and MARCKS-related protein (MARCKSL1), exhibit strong binding with IGF2BPs around their m6A motifs in control cells. Knocking down of each individual IGF2BPs in Hela (cervical cancer) and HepG2 (liver cancer) cells significantly repressed MYC expression."	M6ADIS0006	33051595; 29476152	.
M6ACROT02197	REG00012	M6ATAR00492	DNA methylation	EPIREG00027	EPITAR00192	.	Up regulation	DNA methylation	Indirect	Inhibition	m6A	DNA methylation indirectly regulates m6A modification through downstream signaling pathways	"We identified Protein tyrosine phosphatase non-receptor type 13 (PTPN13) expression by upregulating the expression of DNMT3A and IGF2BP1 as a novel PTPN13-interacting gene and demonstrated that PTPN13 influences c-Myc expression by directly and competitively binding to IGF2BP1 to decrease the intracellular concentration of functional IGF2BP1. Overexpressing PTPN13 promoted c-Myc mRNA degradation independent of the protein tyrosine phosphatase (PTP) activity of PTPN13. Importantly, we discovered that the PTPN13-IGF2BP1-c-Myc axis was important for cancer cell growth through promoting metabolic reprogramming. METTL3/IGF2BP1/Leukocyte surface antigen CD47 (CD47) mediated EMT transition contributes to the incomplete ablation induced metastasis in HCC cells."	M6ADIS0006	33051595; 33582561	.
M6ACROT02198	REG00012	M6ATAR00586	DNA methylation	EPIREG00027	EPITAR00192	.	Up regulation	DNA methylation	Indirect	Inhibition	m6A	DNA methylation indirectly regulates m6A modification through downstream signaling pathways	"We identified Protein tyrosine phosphatase non-receptor type 13 (PTPN13) expression by upregulating the expression of DNMT3A and IGF2BP1 as a novel PTPN13-interacting gene and demonstrated that PTPN13 influences c-Myc expression by directly and competitively binding to IGF2BP1 to decrease the intracellular concentration of functional IGF2BP1. Overexpressing PTPN13 promoted c-Myc mRNA degradation independent of the protein tyrosine phosphatase (PTP) activity of PTPN13. Importantly, we discovered that the PTPN13-IGF2BP1-c-Myc axis was important for cancer cell growth through promoting metabolic reprogramming. Driven by m6A modification, Circ_MAP3K4 encoded circMAP3K4-455aa, protected HCC cells from cisplatin exposure, and predicted worse prognosis of HCC patients. IGF2BP1 facilitates circMAP3K4 peptide translation, then the circMAP3K4 peptide inhibits AIF cleavage and nuclear distribution"	M6ADIS0006	33051595; 35366894	M6ADRUG0047
M6ACROT02199	REG00012	M6ATAR00295	DNA methylation	EPIREG00027	EPITAR00192	.	Up regulation	DNA methylation	Indirect	Inhibition	m6A	DNA methylation indirectly regulates m6A modification through downstream signaling pathways	"We identified Protein tyrosine phosphatase non-receptor type 13 (PTPN13) expression by upregulating the expression of DNMT3A and IGF2BP1 as a novel PTPN13-interacting gene and demonstrated that PTPN13 influences c-Myc expression by directly and competitively binding to IGF2BP1 to decrease the intracellular concentration of functional IGF2BP1. Overexpressing PTPN13 promoted c-Myc mRNA degradation independent of the protein tyrosine phosphatase (PTP) activity of PTPN13. Importantly, we discovered that the PTPN13-IGF2BP1-c-Myc axis was important for cancer cell growth through promoting metabolic reprogramming. Interleukin enhancer-binding factor 3 (ILF3)-AS1 expression was significantly elevated in HCC tissues,mechanistically, ILF3-AS1 associated with ILF3 mRNA and inhibited its degradation. ILF3-AS1 increased ILF3 m6A level via recruiting N6-methyladenosine (m6A) RNA methyltransferase METTL3. Moreover, IFL3-AS1 enhanced the interaction between ILF3 mRNA and m6A reader IGF2BP1."	M6ADIS0006	33051595; 34491544	.
M6ACROT02200	REG00012	M6ATAR00293	DNA methylation	EPIREG00027	EPITAR00192	.	Up regulation	DNA methylation	Indirect	Inhibition	m6A	DNA methylation indirectly regulates m6A modification through downstream signaling pathways	"We identified Protein tyrosine phosphatase non-receptor type 13 (PTPN13) expression by upregulating the expression of DNMT3A and IGF2BP1 as a novel PTPN13-interacting gene and demonstrated that PTPN13 influences c-Myc expression by directly and competitively binding to IGF2BP1 to decrease the intracellular concentration of functional IGF2BP1. Overexpressing PTPN13 promoted c-Myc mRNA degradation independent of the protein tyrosine phosphatase (PTP) activity of PTPN13. Importantly, we discovered that the PTPN13-IGF2BP1-c-Myc axis was important for cancer cell growth through promoting metabolic reprogramming. m6A-modified AC026356.1 promoted HCC cellular proliferation, migration, and liver metastasis.6A-modified AC026356.1 bound to IGF2BP1. The interaction between m6A-modified AC026356.1 and IGF2BP1 promoted the binding of Interleukin-11 (IL11) mRNA to IGF2BP1, leading to increased IL11 mRNA stability and IL11 secretion."	M6ADIS0006	33051595; 37926706	.
M6ACROT02201	REG00012	M6ATAR00895	DNA methylation	EPIREG00027	EPITAR00192	.	Down regulation	DNA methylation	Indirect	Inhibition	m6A	DNA methylation indirectly regulates m6A modification through downstream signaling pathways	"We identified Protein tyrosine phosphatase non-receptor type 13 (PTPN13) expression by upregulating the expression of DNMT3A and IGF2BP1 as a novel PTPN13-interacting gene and demonstrated that PTPN13 influences c-Myc expression by directly and competitively binding to IGF2BP1 to decrease the intracellular concentration of functional IGF2BP1. Overexpressing PTPN13 promoted c-Myc mRNA degradation independent of the protein tyrosine phosphatase (PTP) activity of PTPN13. Importantly, we discovered that the PTPN13-IGF2BP1-c-Myc axis was important for cancer cell growth through promoting metabolic reprogramming. 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	33051595; 36609413	.
M6ACROT02202	REG00012	M6ATAR01400	DNA methylation	EPIREG00027	EPITAR00192	.	.	DNA methylation	Indirect	Inhibition	m6A	DNA methylation indirectly regulates m6A modification through downstream signaling pathways	"We identified Protein tyrosine phosphatase non-receptor type 13 (PTPN13) expression by upregulating the expression of DNMT3A and IGF2BP1 as a novel PTPN13-interacting gene and demonstrated that PTPN13 influences c-Myc expression by directly and competitively binding to IGF2BP1 to decrease the intracellular concentration of functional IGF2BP1. Overexpressing PTPN13 promoted c-Myc mRNA degradation independent of the protein tyrosine phosphatase (PTP) activity of PTPN13. Importantly, we discovered that the PTPN13-IGF2BP1-c-Myc axis was important for cancer cell growth through promoting metabolic reprogramming. Mechanistically, reduced VIM-AS1 expression stabilized Ephrin type-A receptor 3 (EPHA3) mRNA by enhancing the binding of IGF2BP1 to EPHA3 mRNA, leading to increased expression of EPHA3 mRNA and the promotion of HCC progression.These findings suggest that the downregulation of VIM-AS1 due to hypermethylation at cg02746869 increased EPHA3 mRNA expression via a m6A-dependent mechanism to increase HCC aggressiveness. "	M6ADIS0006	33051595; 39617786	.
M6ACROT02203	REG00006	M6ATAR00063	DNA methylation	EPIREG00029	EPITAR00195	.	Up regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"lncRNA UCA1 recruited DNA methyltransferase (DNMT1, DNMT3A, and DNMT3B) to the METTL14 promoter region to inhibit METTL14 expression in breast cancer. In breast cancer, hsa-miR-146a-5p modulated by METTL14 promoted cell migration and invasion."	M6ADIS0065	35022519; 32323801	.
M6ACROT02204	REG00006	M6ATAR00223	DNA methylation	EPIREG00029	EPITAR00195	.	Up regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"lncRNA UCA1 recruited DNA methyltransferase (DNMT1, DNMT3A, and DNMT3B) to the METTL14 promoter region to inhibit METTL14 expression in breast cancer. LNC942-METTL14-C-X-C chemokine receptor type 4 (CXCR4)/CYP1B1 signaling axis, which provides new targets and crosstalk m6A epigenetic modification mechanism for breast cancer prevention and treatment."	M6ADIS0065	35022519; 32576970	.
M6ACROT02205	REG00006	M6ATAR00217	DNA methylation	EPIREG00029	EPITAR00195	.	Up regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"lncRNA UCA1 recruited DNA methyltransferase (DNMT1, DNMT3A, and DNMT3B) to the METTL14 promoter region to inhibit METTL14 expression in breast cancer. LNC942-METTL14-CXCR4/Cytochrome P450 1B1 (CYP1B1) signaling axis, which provides new targets and crosstalk m6A epigenetic modification mechanism for breast cancer prevention and treatment."	M6ADIS0065	35022519; 32576970	.
M6ACROT02206	REG00006	M6ATAR00222	DNA methylation	EPIREG00029	EPITAR00195	.	Down regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"lncRNA UCA1 recruited DNA methyltransferase (DNMT1, DNMT3A, and DNMT3B) to the METTL14 promoter region to inhibit METTL14 expression in breast cancer. m6A-hypomethylation regulated FGFR4 phosphorylates GSK-3beta and activates Catenin beta-1 (CTNNB1/Beta-catenin)/TCF4-SLC7A11/FPN1 signaling to drive anti-HER2 resistance. Knockdown of METTL14 significantly increased the expression level of FGFR4 in HER2-positive breast cancer cells. FGFR4 reduced the sensitivity of HER2-positive breast cancer to trastuzumab plus pertuzumab or tucatinib. These results pinpoint a mechanism of anti-HER2 resistance and provide a strategy for overcoming resistance via FGFR4 inhibition in recalcitrant HER2-positive breast cancer."	M6ADIS0065	35022519; 35562334	M6ADRUG0092
M6ACROT02207	REG00006	M6ATAR00484	DNA methylation	EPIREG00029	EPITAR00195	.	Down regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"lncRNA UCA1 recruited DNA methyltransferase (DNMT1, DNMT3A, and DNMT3B) to the METTL14 promoter region to inhibit METTL14 expression in breast cancer. m6A-hypomethylation regulated FGFR4 phosphorylates GSK-3beta and activates beta-catenin/TCF4-Cystine/glutamate transporter (SLC7A11)/FPN1 signaling to drive anti-HER2 resistance. Knockdown of METTL14 significantly increased the expression level of FGFR4 in HER2-positive breast cancer cells. FGFR4 reduced the sensitivity of HER2-positive breast cancer to trastuzumab plus pertuzumab or tucatinib. These results pinpoint a mechanism of anti-HER2 resistance and provide a strategy for overcoming resistance via FGFR4 inhibition in recalcitrant HER2-positive breast cancer."	M6ADIS0065	35022519; 35562334	M6ADRUG0092
M6ACROT02208	REG00006	M6ATAR00498	DNA methylation	EPIREG00029	EPITAR00195	.	Down regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"lncRNA UCA1 recruited DNA methyltransferase (DNMT1, DNMT3A, and DNMT3B) to the METTL14 promoter region to inhibit METTL14 expression in breast cancer. m6A-hypomethylation regulated FGFR4 phosphorylates GSK-3beta and activates beta-catenin/TCF4-SLC7A11/Solute carrier family 40 member 1 (FPN1) signaling to drive anti-HER2 resistance. Knockdown of METTL14 significantly increased the expression level of FGFR4 in HER2-positive breast cancer cells. FGFR4 reduced the sensitivity of HER2-positive breast cancer to trastuzumab plus pertuzumab or tucatinib. These results pinpoint a mechanism of anti-HER2 resistance and provide a strategy for overcoming resistance via FGFR4 inhibition in recalcitrant HER2-positive breast cancer."	M6ADIS0065	35022519; 35562334	M6ADRUG0092
M6ACROT02209	REG00006	M6ATAR00526	DNA methylation	EPIREG00029	EPITAR00195	.	Down regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"lncRNA UCA1 recruited DNA methyltransferase (DNMT1, DNMT3A, and DNMT3B) to the METTL14 promoter region to inhibit METTL14 expression in breast cancer. m6A-hypomethylation regulated Fibroblast growth factor receptor 4 (FGFR4) phosphorylates GSK-3beta and activates beta-catenin/TCF4-SLC7A11/FPN1 signaling to drive anti-HER2 resistance. Knockdown of METTL14 significantly increased the expression level of FGFR4 in HER2-positive breast cancer cells. FGFR4 reduced the sensitivity of HER2-positive breast cancer to trastuzumab plus pertuzumab or tucatinib. These results pinpoint a mechanism of anti-HER2 resistance and provide a strategy for overcoming resistance via FGFR4 inhibition in recalcitrant HER2-positive breast cancer."	M6ADIS0065	35022519; 35562334	M6ADRUG0095
M6ACROT02210	REG00006	M6ATAR00268	DNA methylation	EPIREG00029	EPITAR00195	.	Down regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"lncRNA UCA1 recruited DNA methyltransferase (DNMT1, DNMT3A, and DNMT3B) to the METTL14 promoter region to inhibit METTL14 expression in breast cancer. m6A-hypomethylation regulated FGFR4 phosphorylates Glycogen synthase kinase-3 beta (GSK3Beta/GSK3B) and activates beta-catenin/TCF4-SLC7A11/FPN1 signaling to drive anti-HER2 resistance. Knockdown of METTL14 significantly increased the expression level of FGFR4 in HER2-positive breast cancer cells. FGFR4 reduced the sensitivity of HER2-positive breast cancer to trastuzumab plus pertuzumab or tucatinib. These results pinpoint a mechanism of anti-HER2 resistance and provide a strategy for overcoming resistance via FGFR4 inhibition in recalcitrant HER2-positive breast cancer."	M6ADIS0065	35022519; 35562334	M6ADRUG0095
M6ACROT02211	REG00006	M6ATAR00222	DNA methylation	EPIREG00029	EPITAR00195	.	Down regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"lncRNA UCA1 recruited DNA methyltransferase (DNMT1, DNMT3A, and DNMT3B) to the METTL14 promoter region to inhibit METTL14 expression in breast cancer. m6A-hypomethylation regulated FGFR4 phosphorylates GSK-3beta and activates Catenin beta-1 (CTNNB1/Beta-catenin)/TCF4-SLC7A11/FPN1 signaling to drive anti-HER2 resistance. Knockdown of METTL14 significantly increased the expression level of FGFR4 in HER2-positive breast cancer cells. FGFR4 reduced the sensitivity of HER2-positive breast cancer to trastuzumab plus pertuzumab or tucatinib. These results pinpoint a mechanism of anti-HER2 resistance and provide a strategy for overcoming resistance via FGFR4 inhibition in recalcitrant HER2-positive breast cancer."	M6ADIS0065	35022519; 35562334	M6ADRUG0095
M6ACROT02212	REG00006	M6ATAR00484	DNA methylation	EPIREG00029	EPITAR00195	.	Down regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"lncRNA UCA1 recruited DNA methyltransferase (DNMT1, DNMT3A, and DNMT3B) to the METTL14 promoter region to inhibit METTL14 expression in breast cancer. m6A-hypomethylation regulated FGFR4 phosphorylates GSK-3beta and activates beta-catenin/TCF4-Cystine/glutamate transporter (SLC7A11)/FPN1 signaling to drive anti-HER2 resistance. Knockdown of METTL14 significantly increased the expression level of FGFR4 in HER2-positive breast cancer cells. FGFR4 reduced the sensitivity of HER2-positive breast cancer to trastuzumab plus pertuzumab or tucatinib. These results pinpoint a mechanism of anti-HER2 resistance and provide a strategy for overcoming resistance via FGFR4 inhibition in recalcitrant HER2-positive breast cancer."	M6ADIS0065	35022519; 35562334	M6ADRUG0095
M6ACROT02213	REG00006	M6ATAR00498	DNA methylation	EPIREG00029	EPITAR00195	.	Down regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"lncRNA UCA1 recruited DNA methyltransferase (DNMT1, DNMT3A, and DNMT3B) to the METTL14 promoter region to inhibit METTL14 expression in breast cancer. m6A-hypomethylation regulated FGFR4 phosphorylates GSK-3beta and activates beta-catenin/TCF4-SLC7A11/Solute carrier family 40 member 1 (FPN1) signaling to drive anti-HER2 resistance. Knockdown of METTL14 significantly increased the expression level of FGFR4 in HER2-positive breast cancer cells. FGFR4 reduced the sensitivity of HER2-positive breast cancer to trastuzumab plus pertuzumab or tucatinib. These results pinpoint a mechanism of anti-HER2 resistance and provide a strategy for overcoming resistance via FGFR4 inhibition in recalcitrant HER2-positive breast cancer."	M6ADIS0065	35022519; 35562334	M6ADRUG0095
M6ACROT02214	REG00006	M6ATAR00560	DNA methylation	EPIREG00029	EPITAR00195	.	Up regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"lncRNA UCA1 recruited DNA methyltransferase (DNMT1, DNMT3A, and DNMT3B) to the METTL14 promoter region to inhibit METTL14 expression in breast cancer. In breast cancer, accordingly YTHDF1 knockdown sensitizes breast cancer cells to Adriamycin and Cisplatin as well as Olaparib, a PARP inhibitor. Transcription factor E2F8 (E2F8) is a target molecule by YTHDF1 which modulates E2F8 mRNA stability and DNA damage repair in a METTL14-dependent manner."	M6ADIS0065	35022519; 35279688	M6ADRUG0097
M6ACROT02215	REG00006	M6ATAR00526	DNA methylation	EPIREG00029	EPITAR00195	.	Down regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"lncRNA UCA1 recruited DNA methyltransferase (DNMT1, DNMT3A, and DNMT3B) to the METTL14 promoter region to inhibit METTL14 expression in breast cancer. m6A-hypomethylation regulated Fibroblast growth factor receptor 4 (FGFR4) phosphorylates GSK-3beta and activates beta-catenin/TCF4-SLC7A11/FPN1 signaling to drive anti-HER2 resistance. Knockdown of METTL14 significantly increased the expression level of FGFR4 in HER2-positive breast cancer cells. FGFR4 reduced the sensitivity of HER2-positive breast cancer to trastuzumab plus pertuzumab or tucatinib. These results pinpoint a mechanism of anti-HER2 resistance and provide a strategy for overcoming resistance via FGFR4 inhibition in recalcitrant HER2-positive breast cancer."	M6ADIS0065	35022519; 35562334	M6ADRUG0091
M6ACROT02216	REG00006	M6ATAR00560	DNA methylation	EPIREG00029	EPITAR00195	.	Up regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"lncRNA UCA1 recruited DNA methyltransferase (DNMT1, DNMT3A, and DNMT3B) to the METTL14 promoter region to inhibit METTL14 expression in breast cancer. In breast cancer, accordingly YTHDF1 knockdown sensitizes breast cancer cells to Adriamycin and Cisplatin as well as Olaparib, a PARP inhibitor. Transcription factor E2F8 (E2F8) is a target molecule by YTHDF1 which modulates E2F8 mRNA stability and DNA damage repair in a METTL14-dependent manner."	M6ADIS0065	35022519; 35279688	M6ADRUG0047
M6ACROT02217	REG00006	M6ATAR00560	DNA methylation	EPIREG00029	EPITAR00195	.	Up regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"lncRNA UCA1 recruited DNA methyltransferase (DNMT1, DNMT3A, and DNMT3B) to the METTL14 promoter region to inhibit METTL14 expression in breast cancer. In breast cancer, accordingly YTHDF1 knockdown sensitizes breast cancer cells to Adriamycin and Cisplatin as well as Olaparib, a PARP inhibitor. Transcription factor E2F8 (E2F8) is a target molecule by YTHDF1 which modulates E2F8 mRNA stability and DNA damage repair in a METTL14-dependent manner."	M6ADIS0065	35022519; 35279688	M6ADRUG0034
M6ACROT02218	REG00006	M6ATAR00268	DNA methylation	EPIREG00029	EPITAR00195	.	Down regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"lncRNA UCA1 recruited DNA methyltransferase (DNMT1, DNMT3A, and DNMT3B) to the METTL14 promoter region to inhibit METTL14 expression in breast cancer. m6A-hypomethylation regulated FGFR4 phosphorylates Glycogen synthase kinase-3 beta (GSK3Beta/GSK3B) and activates beta-catenin/TCF4-SLC7A11/FPN1 signaling to drive anti-HER2 resistance. Knockdown of METTL14 significantly increased the expression level of FGFR4 in HER2-positive breast cancer cells. FGFR4 reduced the sensitivity of HER2-positive breast cancer to trastuzumab plus pertuzumab or tucatinib. These results pinpoint a mechanism of anti-HER2 resistance and provide a strategy for overcoming resistance via FGFR4 inhibition in recalcitrant HER2-positive breast cancer."	M6ADIS0065	35022519; 35562334	M6ADRUG0091
M6ACROT02219	REG00006	M6ATAR00222	DNA methylation	EPIREG00029	EPITAR00195	.	Down regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"lncRNA UCA1 recruited DNA methyltransferase (DNMT1, DNMT3A, and DNMT3B) to the METTL14 promoter region to inhibit METTL14 expression in breast cancer. m6A-hypomethylation regulated FGFR4 phosphorylates GSK-3beta and activates Catenin beta-1 (CTNNB1/Beta-catenin)/TCF4-SLC7A11/FPN1 signaling to drive anti-HER2 resistance. Knockdown of METTL14 significantly increased the expression level of FGFR4 in HER2-positive breast cancer cells. FGFR4 reduced the sensitivity of HER2-positive breast cancer to trastuzumab plus pertuzumab or tucatinib. These results pinpoint a mechanism of anti-HER2 resistance and provide a strategy for overcoming resistance via FGFR4 inhibition in recalcitrant HER2-positive breast cancer."	M6ADIS0065	35022519; 35562334	M6ADRUG0091
M6ACROT02220	REG00006	M6ATAR00484	DNA methylation	EPIREG00029	EPITAR00195	.	Down regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"lncRNA UCA1 recruited DNA methyltransferase (DNMT1, DNMT3A, and DNMT3B) to the METTL14 promoter region to inhibit METTL14 expression in breast cancer. m6A-hypomethylation regulated FGFR4 phosphorylates GSK-3beta and activates beta-catenin/TCF4-Cystine/glutamate transporter (SLC7A11)/FPN1 signaling to drive anti-HER2 resistance. Knockdown of METTL14 significantly increased the expression level of FGFR4 in HER2-positive breast cancer cells. FGFR4 reduced the sensitivity of HER2-positive breast cancer to trastuzumab plus pertuzumab or tucatinib. These results pinpoint a mechanism of anti-HER2 resistance and provide a strategy for overcoming resistance via FGFR4 inhibition in recalcitrant HER2-positive breast cancer."	M6ADIS0065	35022519; 35562334	M6ADRUG0091
M6ACROT02221	REG00006	M6ATAR00498	DNA methylation	EPIREG00029	EPITAR00195	.	Down regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"lncRNA UCA1 recruited DNA methyltransferase (DNMT1, DNMT3A, and DNMT3B) to the METTL14 promoter region to inhibit METTL14 expression in breast cancer. m6A-hypomethylation regulated FGFR4 phosphorylates GSK-3beta and activates beta-catenin/TCF4-SLC7A11/Solute carrier family 40 member 1 (FPN1) signaling to drive anti-HER2 resistance. Knockdown of METTL14 significantly increased the expression level of FGFR4 in HER2-positive breast cancer cells. FGFR4 reduced the sensitivity of HER2-positive breast cancer to trastuzumab plus pertuzumab or tucatinib. These results pinpoint a mechanism of anti-HER2 resistance and provide a strategy for overcoming resistance via FGFR4 inhibition in recalcitrant HER2-positive breast cancer."	M6ADIS0065	35022519; 35562334	M6ADRUG0091
M6ACROT02222	REG00006	M6ATAR00526	DNA methylation	EPIREG00029	EPITAR00195	.	Down regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"lncRNA UCA1 recruited DNA methyltransferase (DNMT1, DNMT3A, and DNMT3B) to the METTL14 promoter region to inhibit METTL14 expression in breast cancer. m6A-hypomethylation regulated Fibroblast growth factor receptor 4 (FGFR4) phosphorylates GSK-3beta and activates beta-catenin/TCF4-SLC7A11/FPN1 signaling to drive anti-HER2 resistance. Knockdown of METTL14 significantly increased the expression level of FGFR4 in HER2-positive breast cancer cells. FGFR4 reduced the sensitivity of HER2-positive breast cancer to trastuzumab plus pertuzumab or tucatinib. These results pinpoint a mechanism of anti-HER2 resistance and provide a strategy for overcoming resistance via FGFR4 inhibition in recalcitrant HER2-positive breast cancer."	M6ADIS0065	35022519; 35562334	M6ADRUG0092
M6ACROT02223	REG00006	M6ATAR00268	DNA methylation	EPIREG00029	EPITAR00195	.	Down regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"lncRNA UCA1 recruited DNA methyltransferase (DNMT1, DNMT3A, and DNMT3B) to the METTL14 promoter region to inhibit METTL14 expression in breast cancer. m6A-hypomethylation regulated FGFR4 phosphorylates Glycogen synthase kinase-3 beta (GSK3Beta/GSK3B) and activates beta-catenin/TCF4-SLC7A11/FPN1 signaling to drive anti-HER2 resistance. Knockdown of METTL14 significantly increased the expression level of FGFR4 in HER2-positive breast cancer cells. FGFR4 reduced the sensitivity of HER2-positive breast cancer to trastuzumab plus pertuzumab or tucatinib. These results pinpoint a mechanism of anti-HER2 resistance and provide a strategy for overcoming resistance via FGFR4 inhibition in recalcitrant HER2-positive breast cancer."	M6ADIS0065	35022519; 35562334	M6ADRUG0092
M6ACROT02224	REG00006	M6ATAR00897	DNA methylation	EPIREG00029	EPITAR00195	.	Up regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"lncRNA UCA1 recruited DNA methyltransferase (DNMT1, DNMT3A, and DNMT3B) to the METTL14 promoter region to inhibit METTL14 expression in breast cancer. N6-methyladenosine (m6A) methylation of RNA by the methyltransferase complex (MTC), with core components including METTL3-METTL14 heterodimers and Wilms' tumor 1-associated protein (WTAP), contributes to breast tumorigenesis.depletion of METTL3a globally disrupts m6A deposition, and METTL3a mediates mammalian target of rapamycin (mTOR) activation via m6A-mediated suppression of Transmembrane protein 127 (TMEM127) expression."	M6ADIS0065	35022519; 37589705	M6ADRUG0044
M6ACROT02225	REG00006	M6ATAR01330	DNA methylation	EPIREG00029	EPITAR00195	.	.	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"lncRNA UCA1 recruited DNA methyltransferase (DNMT1, DNMT3A, and DNMT3B) to the METTL14 promoter region to inhibit METTL14 expression in breast cancer. METTL3/METTL14 increased ER-phagy machinery formation by promoting m6A modification of the ER-phagy regulators Calcium-binding and coiled-coil domain-containing protein 1 (CALCOCO1) and p62, thus enhancing their mRNA stability. The chemotherapeutic drug paclitaxel (PTX) could induce ER stress and increase .the combination of METTL3/METTL14 inhibitors with PTX demonstrated a significant synergistic therapeutic effect in both BC cells and xenograft mice."	M6ADIS0065	35022519; 38582397	M6ADRUG0089
M6ACROT02226	REG00006	M6ATAR00410	DNA methylation	EPIREG00029	EPITAR00195	.	.	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"lncRNA UCA1 recruited DNA methyltransferase (DNMT1, DNMT3A, and DNMT3B) to the METTL14 promoter region to inhibit METTL14 expression in breast cancer. METTL3/METTL14 increased ER-phagy machinery formation by promoting m6A modification of the ER-phagy regulators CALCOCO1 and Sequestosome-1 (SQSTM1), thus enhancing their mRNA stability. The chemotherapeutic drug paclitaxel (PTX) could induce ER stress and increase .the combination of METTL3/METTL14 inhibitors with PTX demonstrated a significant synergistic therapeutic effect in both BC cells and xenograft mice."	M6ADIS0065	35022519; 38582397	M6ADRUG0089
M6ACROT02227	REG00006	M6ATAR00063	DNA methylation	EPIREG00027	EPITAR00195	.	Up regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"lncRNA UCA1 recruited DNA methyltransferase (DNMT1, DNMT3A, and DNMT3B) to the METTL14 promoter region to inhibit METTL14 expression in breast cancer. In breast cancer, hsa-miR-146a-5p modulated by METTL14 promoted cell migration and invasion."	M6ADIS0065	35022519; 32323801	.
M6ACROT02228	REG00006	M6ATAR00223	DNA methylation	EPIREG00027	EPITAR00195	.	Up regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"lncRNA UCA1 recruited DNA methyltransferase (DNMT1, DNMT3A, and DNMT3B) to the METTL14 promoter region to inhibit METTL14 expression in breast cancer. LNC942-METTL14-C-X-C chemokine receptor type 4 (CXCR4)/CYP1B1 signaling axis, which provides new targets and crosstalk m6A epigenetic modification mechanism for breast cancer prevention and treatment."	M6ADIS0065	35022519; 32576970	.
M6ACROT02229	REG00006	M6ATAR00217	DNA methylation	EPIREG00027	EPITAR00195	.	Up regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"lncRNA UCA1 recruited DNA methyltransferase (DNMT1, DNMT3A, and DNMT3B) to the METTL14 promoter region to inhibit METTL14 expression in breast cancer. LNC942-METTL14-CXCR4/Cytochrome P450 1B1 (CYP1B1) signaling axis, which provides new targets and crosstalk m6A epigenetic modification mechanism for breast cancer prevention and treatment."	M6ADIS0065	35022519; 32576970	.
M6ACROT02230	REG00006	M6ATAR00222	DNA methylation	EPIREG00027	EPITAR00195	.	Down regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"lncRNA UCA1 recruited DNA methyltransferase (DNMT1, DNMT3A, and DNMT3B) to the METTL14 promoter region to inhibit METTL14 expression in breast cancer. m6A-hypomethylation regulated FGFR4 phosphorylates GSK-3beta and activates Catenin beta-1 (CTNNB1/Beta-catenin)/TCF4-SLC7A11/FPN1 signaling to drive anti-HER2 resistance. Knockdown of METTL14 significantly increased the expression level of FGFR4 in HER2-positive breast cancer cells. FGFR4 reduced the sensitivity of HER2-positive breast cancer to trastuzumab plus pertuzumab or tucatinib. These results pinpoint a mechanism of anti-HER2 resistance and provide a strategy for overcoming resistance via FGFR4 inhibition in recalcitrant HER2-positive breast cancer."	M6ADIS0065	35022519; 35562334	M6ADRUG0092
M6ACROT02231	REG00006	M6ATAR00484	DNA methylation	EPIREG00027	EPITAR00195	.	Down regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"lncRNA UCA1 recruited DNA methyltransferase (DNMT1, DNMT3A, and DNMT3B) to the METTL14 promoter region to inhibit METTL14 expression in breast cancer. m6A-hypomethylation regulated FGFR4 phosphorylates GSK-3beta and activates beta-catenin/TCF4-Cystine/glutamate transporter (SLC7A11)/FPN1 signaling to drive anti-HER2 resistance. Knockdown of METTL14 significantly increased the expression level of FGFR4 in HER2-positive breast cancer cells. FGFR4 reduced the sensitivity of HER2-positive breast cancer to trastuzumab plus pertuzumab or tucatinib. These results pinpoint a mechanism of anti-HER2 resistance and provide a strategy for overcoming resistance via FGFR4 inhibition in recalcitrant HER2-positive breast cancer."	M6ADIS0065	35022519; 35562334	M6ADRUG0092
M6ACROT02232	REG00006	M6ATAR00498	DNA methylation	EPIREG00027	EPITAR00195	.	Down regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"lncRNA UCA1 recruited DNA methyltransferase (DNMT1, DNMT3A, and DNMT3B) to the METTL14 promoter region to inhibit METTL14 expression in breast cancer. m6A-hypomethylation regulated FGFR4 phosphorylates GSK-3beta and activates beta-catenin/TCF4-SLC7A11/Solute carrier family 40 member 1 (FPN1) signaling to drive anti-HER2 resistance. Knockdown of METTL14 significantly increased the expression level of FGFR4 in HER2-positive breast cancer cells. FGFR4 reduced the sensitivity of HER2-positive breast cancer to trastuzumab plus pertuzumab or tucatinib. These results pinpoint a mechanism of anti-HER2 resistance and provide a strategy for overcoming resistance via FGFR4 inhibition in recalcitrant HER2-positive breast cancer."	M6ADIS0065	35022519; 35562334	M6ADRUG0092
M6ACROT02233	REG00006	M6ATAR00526	DNA methylation	EPIREG00027	EPITAR00195	.	Down regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"lncRNA UCA1 recruited DNA methyltransferase (DNMT1, DNMT3A, and DNMT3B) to the METTL14 promoter region to inhibit METTL14 expression in breast cancer. m6A-hypomethylation regulated Fibroblast growth factor receptor 4 (FGFR4) phosphorylates GSK-3beta and activates beta-catenin/TCF4-SLC7A11/FPN1 signaling to drive anti-HER2 resistance. Knockdown of METTL14 significantly increased the expression level of FGFR4 in HER2-positive breast cancer cells. FGFR4 reduced the sensitivity of HER2-positive breast cancer to trastuzumab plus pertuzumab or tucatinib. These results pinpoint a mechanism of anti-HER2 resistance and provide a strategy for overcoming resistance via FGFR4 inhibition in recalcitrant HER2-positive breast cancer."	M6ADIS0065	35022519; 35562334	M6ADRUG0095
M6ACROT02234	REG00006	M6ATAR00268	DNA methylation	EPIREG00027	EPITAR00195	.	Down regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"lncRNA UCA1 recruited DNA methyltransferase (DNMT1, DNMT3A, and DNMT3B) to the METTL14 promoter region to inhibit METTL14 expression in breast cancer. m6A-hypomethylation regulated FGFR4 phosphorylates Glycogen synthase kinase-3 beta (GSK3Beta/GSK3B) and activates beta-catenin/TCF4-SLC7A11/FPN1 signaling to drive anti-HER2 resistance. Knockdown of METTL14 significantly increased the expression level of FGFR4 in HER2-positive breast cancer cells. FGFR4 reduced the sensitivity of HER2-positive breast cancer to trastuzumab plus pertuzumab or tucatinib. These results pinpoint a mechanism of anti-HER2 resistance and provide a strategy for overcoming resistance via FGFR4 inhibition in recalcitrant HER2-positive breast cancer."	M6ADIS0065	35022519; 35562334	M6ADRUG0095
M6ACROT02235	REG00006	M6ATAR00222	DNA methylation	EPIREG00027	EPITAR00195	.	Down regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"lncRNA UCA1 recruited DNA methyltransferase (DNMT1, DNMT3A, and DNMT3B) to the METTL14 promoter region to inhibit METTL14 expression in breast cancer. m6A-hypomethylation regulated FGFR4 phosphorylates GSK-3beta and activates Catenin beta-1 (CTNNB1/Beta-catenin)/TCF4-SLC7A11/FPN1 signaling to drive anti-HER2 resistance. Knockdown of METTL14 significantly increased the expression level of FGFR4 in HER2-positive breast cancer cells. FGFR4 reduced the sensitivity of HER2-positive breast cancer to trastuzumab plus pertuzumab or tucatinib. These results pinpoint a mechanism of anti-HER2 resistance and provide a strategy for overcoming resistance via FGFR4 inhibition in recalcitrant HER2-positive breast cancer."	M6ADIS0065	35022519; 35562334	M6ADRUG0095
M6ACROT02236	REG00006	M6ATAR00484	DNA methylation	EPIREG00027	EPITAR00195	.	Down regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"lncRNA UCA1 recruited DNA methyltransferase (DNMT1, DNMT3A, and DNMT3B) to the METTL14 promoter region to inhibit METTL14 expression in breast cancer. m6A-hypomethylation regulated FGFR4 phosphorylates GSK-3beta and activates beta-catenin/TCF4-Cystine/glutamate transporter (SLC7A11)/FPN1 signaling to drive anti-HER2 resistance. Knockdown of METTL14 significantly increased the expression level of FGFR4 in HER2-positive breast cancer cells. FGFR4 reduced the sensitivity of HER2-positive breast cancer to trastuzumab plus pertuzumab or tucatinib. These results pinpoint a mechanism of anti-HER2 resistance and provide a strategy for overcoming resistance via FGFR4 inhibition in recalcitrant HER2-positive breast cancer."	M6ADIS0065	35022519; 35562334	M6ADRUG0095
M6ACROT02237	REG00006	M6ATAR00498	DNA methylation	EPIREG00027	EPITAR00195	.	Down regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"lncRNA UCA1 recruited DNA methyltransferase (DNMT1, DNMT3A, and DNMT3B) to the METTL14 promoter region to inhibit METTL14 expression in breast cancer. m6A-hypomethylation regulated FGFR4 phosphorylates GSK-3beta and activates beta-catenin/TCF4-SLC7A11/Solute carrier family 40 member 1 (FPN1) signaling to drive anti-HER2 resistance. Knockdown of METTL14 significantly increased the expression level of FGFR4 in HER2-positive breast cancer cells. FGFR4 reduced the sensitivity of HER2-positive breast cancer to trastuzumab plus pertuzumab or tucatinib. These results pinpoint a mechanism of anti-HER2 resistance and provide a strategy for overcoming resistance via FGFR4 inhibition in recalcitrant HER2-positive breast cancer."	M6ADIS0065	35022519; 35562334	M6ADRUG0095
M6ACROT02238	REG00006	M6ATAR00560	DNA methylation	EPIREG00027	EPITAR00195	.	Up regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"lncRNA UCA1 recruited DNA methyltransferase (DNMT1, DNMT3A, and DNMT3B) to the METTL14 promoter region to inhibit METTL14 expression in breast cancer. In breast cancer, accordingly YTHDF1 knockdown sensitizes breast cancer cells to Adriamycin and Cisplatin as well as Olaparib, a PARP inhibitor. Transcription factor E2F8 (E2F8) is a target molecule by YTHDF1 which modulates E2F8 mRNA stability and DNA damage repair in a METTL14-dependent manner."	M6ADIS0065	35022519; 35279688	M6ADRUG0097
M6ACROT02239	REG00006	M6ATAR00526	DNA methylation	EPIREG00027	EPITAR00195	.	Down regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"lncRNA UCA1 recruited DNA methyltransferase (DNMT1, DNMT3A, and DNMT3B) to the METTL14 promoter region to inhibit METTL14 expression in breast cancer. m6A-hypomethylation regulated Fibroblast growth factor receptor 4 (FGFR4) phosphorylates GSK-3beta and activates beta-catenin/TCF4-SLC7A11/FPN1 signaling to drive anti-HER2 resistance. Knockdown of METTL14 significantly increased the expression level of FGFR4 in HER2-positive breast cancer cells. FGFR4 reduced the sensitivity of HER2-positive breast cancer to trastuzumab plus pertuzumab or tucatinib. These results pinpoint a mechanism of anti-HER2 resistance and provide a strategy for overcoming resistance via FGFR4 inhibition in recalcitrant HER2-positive breast cancer."	M6ADIS0065	35022519; 35562334	M6ADRUG0091
M6ACROT02240	REG00006	M6ATAR00560	DNA methylation	EPIREG00027	EPITAR00195	.	Up regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"lncRNA UCA1 recruited DNA methyltransferase (DNMT1, DNMT3A, and DNMT3B) to the METTL14 promoter region to inhibit METTL14 expression in breast cancer. In breast cancer, accordingly YTHDF1 knockdown sensitizes breast cancer cells to Adriamycin and Cisplatin as well as Olaparib, a PARP inhibitor. Transcription factor E2F8 (E2F8) is a target molecule by YTHDF1 which modulates E2F8 mRNA stability and DNA damage repair in a METTL14-dependent manner."	M6ADIS0065	35022519; 35279688	M6ADRUG0047
M6ACROT02241	REG00006	M6ATAR00560	DNA methylation	EPIREG00027	EPITAR00195	.	Up regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"lncRNA UCA1 recruited DNA methyltransferase (DNMT1, DNMT3A, and DNMT3B) to the METTL14 promoter region to inhibit METTL14 expression in breast cancer. In breast cancer, accordingly YTHDF1 knockdown sensitizes breast cancer cells to Adriamycin and Cisplatin as well as Olaparib, a PARP inhibitor. Transcription factor E2F8 (E2F8) is a target molecule by YTHDF1 which modulates E2F8 mRNA stability and DNA damage repair in a METTL14-dependent manner."	M6ADIS0065	35022519; 35279688	M6ADRUG0034
M6ACROT02242	REG00006	M6ATAR00268	DNA methylation	EPIREG00027	EPITAR00195	.	Down regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"lncRNA UCA1 recruited DNA methyltransferase (DNMT1, DNMT3A, and DNMT3B) to the METTL14 promoter region to inhibit METTL14 expression in breast cancer. m6A-hypomethylation regulated FGFR4 phosphorylates Glycogen synthase kinase-3 beta (GSK3Beta/GSK3B) and activates beta-catenin/TCF4-SLC7A11/FPN1 signaling to drive anti-HER2 resistance. Knockdown of METTL14 significantly increased the expression level of FGFR4 in HER2-positive breast cancer cells. FGFR4 reduced the sensitivity of HER2-positive breast cancer to trastuzumab plus pertuzumab or tucatinib. These results pinpoint a mechanism of anti-HER2 resistance and provide a strategy for overcoming resistance via FGFR4 inhibition in recalcitrant HER2-positive breast cancer."	M6ADIS0065	35022519; 35562334	M6ADRUG0091
M6ACROT02243	REG00006	M6ATAR00222	DNA methylation	EPIREG00027	EPITAR00195	.	Down regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"lncRNA UCA1 recruited DNA methyltransferase (DNMT1, DNMT3A, and DNMT3B) to the METTL14 promoter region to inhibit METTL14 expression in breast cancer. m6A-hypomethylation regulated FGFR4 phosphorylates GSK-3beta and activates Catenin beta-1 (CTNNB1/Beta-catenin)/TCF4-SLC7A11/FPN1 signaling to drive anti-HER2 resistance. Knockdown of METTL14 significantly increased the expression level of FGFR4 in HER2-positive breast cancer cells. FGFR4 reduced the sensitivity of HER2-positive breast cancer to trastuzumab plus pertuzumab or tucatinib. These results pinpoint a mechanism of anti-HER2 resistance and provide a strategy for overcoming resistance via FGFR4 inhibition in recalcitrant HER2-positive breast cancer."	M6ADIS0065	35022519; 35562334	M6ADRUG0091
M6ACROT02244	REG00006	M6ATAR00484	DNA methylation	EPIREG00027	EPITAR00195	.	Down regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"lncRNA UCA1 recruited DNA methyltransferase (DNMT1, DNMT3A, and DNMT3B) to the METTL14 promoter region to inhibit METTL14 expression in breast cancer. m6A-hypomethylation regulated FGFR4 phosphorylates GSK-3beta and activates beta-catenin/TCF4-Cystine/glutamate transporter (SLC7A11)/FPN1 signaling to drive anti-HER2 resistance. Knockdown of METTL14 significantly increased the expression level of FGFR4 in HER2-positive breast cancer cells. FGFR4 reduced the sensitivity of HER2-positive breast cancer to trastuzumab plus pertuzumab or tucatinib. These results pinpoint a mechanism of anti-HER2 resistance and provide a strategy for overcoming resistance via FGFR4 inhibition in recalcitrant HER2-positive breast cancer."	M6ADIS0065	35022519; 35562334	M6ADRUG0091
M6ACROT02245	REG00006	M6ATAR00498	DNA methylation	EPIREG00027	EPITAR00195	.	Down regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"lncRNA UCA1 recruited DNA methyltransferase (DNMT1, DNMT3A, and DNMT3B) to the METTL14 promoter region to inhibit METTL14 expression in breast cancer. m6A-hypomethylation regulated FGFR4 phosphorylates GSK-3beta and activates beta-catenin/TCF4-SLC7A11/Solute carrier family 40 member 1 (FPN1) signaling to drive anti-HER2 resistance. Knockdown of METTL14 significantly increased the expression level of FGFR4 in HER2-positive breast cancer cells. FGFR4 reduced the sensitivity of HER2-positive breast cancer to trastuzumab plus pertuzumab or tucatinib. These results pinpoint a mechanism of anti-HER2 resistance and provide a strategy for overcoming resistance via FGFR4 inhibition in recalcitrant HER2-positive breast cancer."	M6ADIS0065	35022519; 35562334	M6ADRUG0091
M6ACROT02246	REG00006	M6ATAR00526	DNA methylation	EPIREG00027	EPITAR00195	.	Down regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"lncRNA UCA1 recruited DNA methyltransferase (DNMT1, DNMT3A, and DNMT3B) to the METTL14 promoter region to inhibit METTL14 expression in breast cancer. m6A-hypomethylation regulated Fibroblast growth factor receptor 4 (FGFR4) phosphorylates GSK-3beta and activates beta-catenin/TCF4-SLC7A11/FPN1 signaling to drive anti-HER2 resistance. Knockdown of METTL14 significantly increased the expression level of FGFR4 in HER2-positive breast cancer cells. FGFR4 reduced the sensitivity of HER2-positive breast cancer to trastuzumab plus pertuzumab or tucatinib. These results pinpoint a mechanism of anti-HER2 resistance and provide a strategy for overcoming resistance via FGFR4 inhibition in recalcitrant HER2-positive breast cancer."	M6ADIS0065	35022519; 35562334	M6ADRUG0092
M6ACROT02247	REG00006	M6ATAR00268	DNA methylation	EPIREG00027	EPITAR00195	.	Down regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"lncRNA UCA1 recruited DNA methyltransferase (DNMT1, DNMT3A, and DNMT3B) to the METTL14 promoter region to inhibit METTL14 expression in breast cancer. m6A-hypomethylation regulated FGFR4 phosphorylates Glycogen synthase kinase-3 beta (GSK3Beta/GSK3B) and activates beta-catenin/TCF4-SLC7A11/FPN1 signaling to drive anti-HER2 resistance. Knockdown of METTL14 significantly increased the expression level of FGFR4 in HER2-positive breast cancer cells. FGFR4 reduced the sensitivity of HER2-positive breast cancer to trastuzumab plus pertuzumab or tucatinib. These results pinpoint a mechanism of anti-HER2 resistance and provide a strategy for overcoming resistance via FGFR4 inhibition in recalcitrant HER2-positive breast cancer."	M6ADIS0065	35022519; 35562334	M6ADRUG0092
M6ACROT02248	REG00006	M6ATAR00897	DNA methylation	EPIREG00027	EPITAR00195	.	Up regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"lncRNA UCA1 recruited DNA methyltransferase (DNMT1, DNMT3A, and DNMT3B) to the METTL14 promoter region to inhibit METTL14 expression in breast cancer. N6-methyladenosine (m6A) methylation of RNA by the methyltransferase complex (MTC), with core components including METTL3-METTL14 heterodimers and Wilms' tumor 1-associated protein (WTAP), contributes to breast tumorigenesis.depletion of METTL3a globally disrupts m6A deposition, and METTL3a mediates mammalian target of rapamycin (mTOR) activation via m6A-mediated suppression of Transmembrane protein 127 (TMEM127) expression."	M6ADIS0065	35022519; 37589705	M6ADRUG0044
M6ACROT02249	REG00006	M6ATAR01330	DNA methylation	EPIREG00027	EPITAR00195	.	.	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"lncRNA UCA1 recruited DNA methyltransferase (DNMT1, DNMT3A, and DNMT3B) to the METTL14 promoter region to inhibit METTL14 expression in breast cancer. METTL3/METTL14 increased ER-phagy machinery formation by promoting m6A modification of the ER-phagy regulators Calcium-binding and coiled-coil domain-containing protein 1 (CALCOCO1) and p62, thus enhancing their mRNA stability. The chemotherapeutic drug paclitaxel (PTX) could induce ER stress and increase .the combination of METTL3/METTL14 inhibitors with PTX demonstrated a significant synergistic therapeutic effect in both BC cells and xenograft mice."	M6ADIS0065	35022519; 38582397	M6ADRUG0089
M6ACROT02250	REG00006	M6ATAR00410	DNA methylation	EPIREG00027	EPITAR00195	.	.	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"lncRNA UCA1 recruited DNA methyltransferase (DNMT1, DNMT3A, and DNMT3B) to the METTL14 promoter region to inhibit METTL14 expression in breast cancer. METTL3/METTL14 increased ER-phagy machinery formation by promoting m6A modification of the ER-phagy regulators CALCOCO1 and Sequestosome-1 (SQSTM1), thus enhancing their mRNA stability. The chemotherapeutic drug paclitaxel (PTX) could induce ER stress and increase .the combination of METTL3/METTL14 inhibitors with PTX demonstrated a significant synergistic therapeutic effect in both BC cells and xenograft mice."	M6ADIS0065	35022519; 38582397	M6ADRUG0089
M6ACROT02251	REG00006	M6ATAR00063	DNA methylation	EPIREG00028	EPITAR00195	.	Up regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"lncRNA UCA1 recruited DNA methyltransferase (DNMT1, DNMT3A, and DNMT3B) to the METTL14 promoter region to inhibit METTL14 expression in breast cancer. In breast cancer, hsa-miR-146a-5p modulated by METTL14 promoted cell migration and invasion."	M6ADIS0065	35022519; 32323801	.
M6ACROT02252	REG00006	M6ATAR00223	DNA methylation	EPIREG00028	EPITAR00195	.	Up regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"lncRNA UCA1 recruited DNA methyltransferase (DNMT1, DNMT3A, and DNMT3B) to the METTL14 promoter region to inhibit METTL14 expression in breast cancer. LNC942-METTL14-C-X-C chemokine receptor type 4 (CXCR4)/CYP1B1 signaling axis, which provides new targets and crosstalk m6A epigenetic modification mechanism for breast cancer prevention and treatment."	M6ADIS0065	35022519; 32576970	.
M6ACROT02253	REG00006	M6ATAR00217	DNA methylation	EPIREG00028	EPITAR00195	.	Up regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"lncRNA UCA1 recruited DNA methyltransferase (DNMT1, DNMT3A, and DNMT3B) to the METTL14 promoter region to inhibit METTL14 expression in breast cancer. LNC942-METTL14-CXCR4/Cytochrome P450 1B1 (CYP1B1) signaling axis, which provides new targets and crosstalk m6A epigenetic modification mechanism for breast cancer prevention and treatment."	M6ADIS0065	35022519; 32576970	.
M6ACROT02254	REG00006	M6ATAR00222	DNA methylation	EPIREG00028	EPITAR00195	.	Down regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"lncRNA UCA1 recruited DNA methyltransferase (DNMT1, DNMT3A, and DNMT3B) to the METTL14 promoter region to inhibit METTL14 expression in breast cancer. m6A-hypomethylation regulated FGFR4 phosphorylates GSK-3beta and activates Catenin beta-1 (CTNNB1/Beta-catenin)/TCF4-SLC7A11/FPN1 signaling to drive anti-HER2 resistance. Knockdown of METTL14 significantly increased the expression level of FGFR4 in HER2-positive breast cancer cells. FGFR4 reduced the sensitivity of HER2-positive breast cancer to trastuzumab plus pertuzumab or tucatinib. These results pinpoint a mechanism of anti-HER2 resistance and provide a strategy for overcoming resistance via FGFR4 inhibition in recalcitrant HER2-positive breast cancer."	M6ADIS0065	35022519; 35562334	M6ADRUG0092
M6ACROT02255	REG00006	M6ATAR00484	DNA methylation	EPIREG00028	EPITAR00195	.	Down regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"lncRNA UCA1 recruited DNA methyltransferase (DNMT1, DNMT3A, and DNMT3B) to the METTL14 promoter region to inhibit METTL14 expression in breast cancer. m6A-hypomethylation regulated FGFR4 phosphorylates GSK-3beta and activates beta-catenin/TCF4-Cystine/glutamate transporter (SLC7A11)/FPN1 signaling to drive anti-HER2 resistance. Knockdown of METTL14 significantly increased the expression level of FGFR4 in HER2-positive breast cancer cells. FGFR4 reduced the sensitivity of HER2-positive breast cancer to trastuzumab plus pertuzumab or tucatinib. These results pinpoint a mechanism of anti-HER2 resistance and provide a strategy for overcoming resistance via FGFR4 inhibition in recalcitrant HER2-positive breast cancer."	M6ADIS0065	35022519; 35562334	M6ADRUG0092
M6ACROT02256	REG00006	M6ATAR00498	DNA methylation	EPIREG00028	EPITAR00195	.	Down regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"lncRNA UCA1 recruited DNA methyltransferase (DNMT1, DNMT3A, and DNMT3B) to the METTL14 promoter region to inhibit METTL14 expression in breast cancer. m6A-hypomethylation regulated FGFR4 phosphorylates GSK-3beta and activates beta-catenin/TCF4-SLC7A11/Solute carrier family 40 member 1 (FPN1) signaling to drive anti-HER2 resistance. Knockdown of METTL14 significantly increased the expression level of FGFR4 in HER2-positive breast cancer cells. FGFR4 reduced the sensitivity of HER2-positive breast cancer to trastuzumab plus pertuzumab or tucatinib. These results pinpoint a mechanism of anti-HER2 resistance and provide a strategy for overcoming resistance via FGFR4 inhibition in recalcitrant HER2-positive breast cancer."	M6ADIS0065	35022519; 35562334	M6ADRUG0092
M6ACROT02257	REG00006	M6ATAR00526	DNA methylation	EPIREG00028	EPITAR00195	.	Down regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"lncRNA UCA1 recruited DNA methyltransferase (DNMT1, DNMT3A, and DNMT3B) to the METTL14 promoter region to inhibit METTL14 expression in breast cancer. m6A-hypomethylation regulated Fibroblast growth factor receptor 4 (FGFR4) phosphorylates GSK-3beta and activates beta-catenin/TCF4-SLC7A11/FPN1 signaling to drive anti-HER2 resistance. Knockdown of METTL14 significantly increased the expression level of FGFR4 in HER2-positive breast cancer cells. FGFR4 reduced the sensitivity of HER2-positive breast cancer to trastuzumab plus pertuzumab or tucatinib. These results pinpoint a mechanism of anti-HER2 resistance and provide a strategy for overcoming resistance via FGFR4 inhibition in recalcitrant HER2-positive breast cancer."	M6ADIS0065	35022519; 35562334	M6ADRUG0095
M6ACROT02258	REG00006	M6ATAR00268	DNA methylation	EPIREG00028	EPITAR00195	.	Down regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"lncRNA UCA1 recruited DNA methyltransferase (DNMT1, DNMT3A, and DNMT3B) to the METTL14 promoter region to inhibit METTL14 expression in breast cancer. m6A-hypomethylation regulated FGFR4 phosphorylates Glycogen synthase kinase-3 beta (GSK3Beta/GSK3B) and activates beta-catenin/TCF4-SLC7A11/FPN1 signaling to drive anti-HER2 resistance. Knockdown of METTL14 significantly increased the expression level of FGFR4 in HER2-positive breast cancer cells. FGFR4 reduced the sensitivity of HER2-positive breast cancer to trastuzumab plus pertuzumab or tucatinib. These results pinpoint a mechanism of anti-HER2 resistance and provide a strategy for overcoming resistance via FGFR4 inhibition in recalcitrant HER2-positive breast cancer."	M6ADIS0065	35022519; 35562334	M6ADRUG0095
M6ACROT02259	REG00006	M6ATAR00222	DNA methylation	EPIREG00028	EPITAR00195	.	Down regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"lncRNA UCA1 recruited DNA methyltransferase (DNMT1, DNMT3A, and DNMT3B) to the METTL14 promoter region to inhibit METTL14 expression in breast cancer. m6A-hypomethylation regulated FGFR4 phosphorylates GSK-3beta and activates Catenin beta-1 (CTNNB1/Beta-catenin)/TCF4-SLC7A11/FPN1 signaling to drive anti-HER2 resistance. Knockdown of METTL14 significantly increased the expression level of FGFR4 in HER2-positive breast cancer cells. FGFR4 reduced the sensitivity of HER2-positive breast cancer to trastuzumab plus pertuzumab or tucatinib. These results pinpoint a mechanism of anti-HER2 resistance and provide a strategy for overcoming resistance via FGFR4 inhibition in recalcitrant HER2-positive breast cancer."	M6ADIS0065	35022519; 35562334	M6ADRUG0095
M6ACROT02260	REG00006	M6ATAR00484	DNA methylation	EPIREG00028	EPITAR00195	.	Down regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"lncRNA UCA1 recruited DNA methyltransferase (DNMT1, DNMT3A, and DNMT3B) to the METTL14 promoter region to inhibit METTL14 expression in breast cancer. m6A-hypomethylation regulated FGFR4 phosphorylates GSK-3beta and activates beta-catenin/TCF4-Cystine/glutamate transporter (SLC7A11)/FPN1 signaling to drive anti-HER2 resistance. Knockdown of METTL14 significantly increased the expression level of FGFR4 in HER2-positive breast cancer cells. FGFR4 reduced the sensitivity of HER2-positive breast cancer to trastuzumab plus pertuzumab or tucatinib. These results pinpoint a mechanism of anti-HER2 resistance and provide a strategy for overcoming resistance via FGFR4 inhibition in recalcitrant HER2-positive breast cancer."	M6ADIS0065	35022519; 35562334	M6ADRUG0095
M6ACROT02261	REG00006	M6ATAR00498	DNA methylation	EPIREG00028	EPITAR00195	.	Down regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"lncRNA UCA1 recruited DNA methyltransferase (DNMT1, DNMT3A, and DNMT3B) to the METTL14 promoter region to inhibit METTL14 expression in breast cancer. m6A-hypomethylation regulated FGFR4 phosphorylates GSK-3beta and activates beta-catenin/TCF4-SLC7A11/Solute carrier family 40 member 1 (FPN1) signaling to drive anti-HER2 resistance. Knockdown of METTL14 significantly increased the expression level of FGFR4 in HER2-positive breast cancer cells. FGFR4 reduced the sensitivity of HER2-positive breast cancer to trastuzumab plus pertuzumab or tucatinib. These results pinpoint a mechanism of anti-HER2 resistance and provide a strategy for overcoming resistance via FGFR4 inhibition in recalcitrant HER2-positive breast cancer."	M6ADIS0065	35022519; 35562334	M6ADRUG0095
M6ACROT02262	REG00006	M6ATAR00560	DNA methylation	EPIREG00028	EPITAR00195	.	Up regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"lncRNA UCA1 recruited DNA methyltransferase (DNMT1, DNMT3A, and DNMT3B) to the METTL14 promoter region to inhibit METTL14 expression in breast cancer. In breast cancer, accordingly YTHDF1 knockdown sensitizes breast cancer cells to Adriamycin and Cisplatin as well as Olaparib, a PARP inhibitor. Transcription factor E2F8 (E2F8) is a target molecule by YTHDF1 which modulates E2F8 mRNA stability and DNA damage repair in a METTL14-dependent manner."	M6ADIS0065	35022519; 35279688	M6ADRUG0097
M6ACROT02263	REG00006	M6ATAR00526	DNA methylation	EPIREG00028	EPITAR00195	.	Down regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"lncRNA UCA1 recruited DNA methyltransferase (DNMT1, DNMT3A, and DNMT3B) to the METTL14 promoter region to inhibit METTL14 expression in breast cancer. m6A-hypomethylation regulated Fibroblast growth factor receptor 4 (FGFR4) phosphorylates GSK-3beta and activates beta-catenin/TCF4-SLC7A11/FPN1 signaling to drive anti-HER2 resistance. Knockdown of METTL14 significantly increased the expression level of FGFR4 in HER2-positive breast cancer cells. FGFR4 reduced the sensitivity of HER2-positive breast cancer to trastuzumab plus pertuzumab or tucatinib. These results pinpoint a mechanism of anti-HER2 resistance and provide a strategy for overcoming resistance via FGFR4 inhibition in recalcitrant HER2-positive breast cancer."	M6ADIS0065	35022519; 35562334	M6ADRUG0091
M6ACROT02264	REG00006	M6ATAR00560	DNA methylation	EPIREG00028	EPITAR00195	.	Up regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"lncRNA UCA1 recruited DNA methyltransferase (DNMT1, DNMT3A, and DNMT3B) to the METTL14 promoter region to inhibit METTL14 expression in breast cancer. In breast cancer, accordingly YTHDF1 knockdown sensitizes breast cancer cells to Adriamycin and Cisplatin as well as Olaparib, a PARP inhibitor. Transcription factor E2F8 (E2F8) is a target molecule by YTHDF1 which modulates E2F8 mRNA stability and DNA damage repair in a METTL14-dependent manner."	M6ADIS0065	35022519; 35279688	M6ADRUG0047
M6ACROT02265	REG00006	M6ATAR00560	DNA methylation	EPIREG00028	EPITAR00195	.	Up regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"lncRNA UCA1 recruited DNA methyltransferase (DNMT1, DNMT3A, and DNMT3B) to the METTL14 promoter region to inhibit METTL14 expression in breast cancer. In breast cancer, accordingly YTHDF1 knockdown sensitizes breast cancer cells to Adriamycin and Cisplatin as well as Olaparib, a PARP inhibitor. Transcription factor E2F8 (E2F8) is a target molecule by YTHDF1 which modulates E2F8 mRNA stability and DNA damage repair in a METTL14-dependent manner."	M6ADIS0065	35022519; 35279688	M6ADRUG0034
M6ACROT02266	REG00006	M6ATAR00268	DNA methylation	EPIREG00028	EPITAR00195	.	Down regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"lncRNA UCA1 recruited DNA methyltransferase (DNMT1, DNMT3A, and DNMT3B) to the METTL14 promoter region to inhibit METTL14 expression in breast cancer. m6A-hypomethylation regulated FGFR4 phosphorylates Glycogen synthase kinase-3 beta (GSK3Beta/GSK3B) and activates beta-catenin/TCF4-SLC7A11/FPN1 signaling to drive anti-HER2 resistance. Knockdown of METTL14 significantly increased the expression level of FGFR4 in HER2-positive breast cancer cells. FGFR4 reduced the sensitivity of HER2-positive breast cancer to trastuzumab plus pertuzumab or tucatinib. These results pinpoint a mechanism of anti-HER2 resistance and provide a strategy for overcoming resistance via FGFR4 inhibition in recalcitrant HER2-positive breast cancer."	M6ADIS0065	35022519; 35562334	M6ADRUG0091
M6ACROT02267	REG00006	M6ATAR00222	DNA methylation	EPIREG00028	EPITAR00195	.	Down regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"lncRNA UCA1 recruited DNA methyltransferase (DNMT1, DNMT3A, and DNMT3B) to the METTL14 promoter region to inhibit METTL14 expression in breast cancer. m6A-hypomethylation regulated FGFR4 phosphorylates GSK-3beta and activates Catenin beta-1 (CTNNB1/Beta-catenin)/TCF4-SLC7A11/FPN1 signaling to drive anti-HER2 resistance. Knockdown of METTL14 significantly increased the expression level of FGFR4 in HER2-positive breast cancer cells. FGFR4 reduced the sensitivity of HER2-positive breast cancer to trastuzumab plus pertuzumab or tucatinib. These results pinpoint a mechanism of anti-HER2 resistance and provide a strategy for overcoming resistance via FGFR4 inhibition in recalcitrant HER2-positive breast cancer."	M6ADIS0065	35022519; 35562334	M6ADRUG0091
M6ACROT02268	REG00006	M6ATAR00484	DNA methylation	EPIREG00028	EPITAR00195	.	Down regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"lncRNA UCA1 recruited DNA methyltransferase (DNMT1, DNMT3A, and DNMT3B) to the METTL14 promoter region to inhibit METTL14 expression in breast cancer. m6A-hypomethylation regulated FGFR4 phosphorylates GSK-3beta and activates beta-catenin/TCF4-Cystine/glutamate transporter (SLC7A11)/FPN1 signaling to drive anti-HER2 resistance. Knockdown of METTL14 significantly increased the expression level of FGFR4 in HER2-positive breast cancer cells. FGFR4 reduced the sensitivity of HER2-positive breast cancer to trastuzumab plus pertuzumab or tucatinib. These results pinpoint a mechanism of anti-HER2 resistance and provide a strategy for overcoming resistance via FGFR4 inhibition in recalcitrant HER2-positive breast cancer."	M6ADIS0065	35022519; 35562334	M6ADRUG0091
M6ACROT02269	REG00006	M6ATAR00498	DNA methylation	EPIREG00028	EPITAR00195	.	Down regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"lncRNA UCA1 recruited DNA methyltransferase (DNMT1, DNMT3A, and DNMT3B) to the METTL14 promoter region to inhibit METTL14 expression in breast cancer. m6A-hypomethylation regulated FGFR4 phosphorylates GSK-3beta and activates beta-catenin/TCF4-SLC7A11/Solute carrier family 40 member 1 (FPN1) signaling to drive anti-HER2 resistance. Knockdown of METTL14 significantly increased the expression level of FGFR4 in HER2-positive breast cancer cells. FGFR4 reduced the sensitivity of HER2-positive breast cancer to trastuzumab plus pertuzumab or tucatinib. These results pinpoint a mechanism of anti-HER2 resistance and provide a strategy for overcoming resistance via FGFR4 inhibition in recalcitrant HER2-positive breast cancer."	M6ADIS0065	35022519; 35562334	M6ADRUG0091
M6ACROT02270	REG00006	M6ATAR00526	DNA methylation	EPIREG00028	EPITAR00195	.	Down regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"lncRNA UCA1 recruited DNA methyltransferase (DNMT1, DNMT3A, and DNMT3B) to the METTL14 promoter region to inhibit METTL14 expression in breast cancer. m6A-hypomethylation regulated Fibroblast growth factor receptor 4 (FGFR4) phosphorylates GSK-3beta and activates beta-catenin/TCF4-SLC7A11/FPN1 signaling to drive anti-HER2 resistance. Knockdown of METTL14 significantly increased the expression level of FGFR4 in HER2-positive breast cancer cells. FGFR4 reduced the sensitivity of HER2-positive breast cancer to trastuzumab plus pertuzumab or tucatinib. These results pinpoint a mechanism of anti-HER2 resistance and provide a strategy for overcoming resistance via FGFR4 inhibition in recalcitrant HER2-positive breast cancer."	M6ADIS0065	35022519; 35562334	M6ADRUG0092
M6ACROT02271	REG00006	M6ATAR00268	DNA methylation	EPIREG00028	EPITAR00195	.	Down regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"lncRNA UCA1 recruited DNA methyltransferase (DNMT1, DNMT3A, and DNMT3B) to the METTL14 promoter region to inhibit METTL14 expression in breast cancer. m6A-hypomethylation regulated FGFR4 phosphorylates Glycogen synthase kinase-3 beta (GSK3Beta/GSK3B) and activates beta-catenin/TCF4-SLC7A11/FPN1 signaling to drive anti-HER2 resistance. Knockdown of METTL14 significantly increased the expression level of FGFR4 in HER2-positive breast cancer cells. FGFR4 reduced the sensitivity of HER2-positive breast cancer to trastuzumab plus pertuzumab or tucatinib. These results pinpoint a mechanism of anti-HER2 resistance and provide a strategy for overcoming resistance via FGFR4 inhibition in recalcitrant HER2-positive breast cancer."	M6ADIS0065	35022519; 35562334	M6ADRUG0092
M6ACROT02272	REG00006	M6ATAR00897	DNA methylation	EPIREG00028	EPITAR00195	.	Up regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"lncRNA UCA1 recruited DNA methyltransferase (DNMT1, DNMT3A, and DNMT3B) to the METTL14 promoter region to inhibit METTL14 expression in breast cancer. N6-methyladenosine (m6A) methylation of RNA by the methyltransferase complex (MTC), with core components including METTL3-METTL14 heterodimers and Wilms' tumor 1-associated protein (WTAP), contributes to breast tumorigenesis.depletion of METTL3a globally disrupts m6A deposition, and METTL3a mediates mammalian target of rapamycin (mTOR) activation via m6A-mediated suppression of Transmembrane protein 127 (TMEM127) expression."	M6ADIS0065	35022519; 37589705	M6ADRUG0044
M6ACROT02273	REG00006	M6ATAR01330	DNA methylation	EPIREG00028	EPITAR00195	.	.	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"lncRNA UCA1 recruited DNA methyltransferase (DNMT1, DNMT3A, and DNMT3B) to the METTL14 promoter region to inhibit METTL14 expression in breast cancer. METTL3/METTL14 increased ER-phagy machinery formation by promoting m6A modification of the ER-phagy regulators Calcium-binding and coiled-coil domain-containing protein 1 (CALCOCO1) and p62, thus enhancing their mRNA stability. The chemotherapeutic drug paclitaxel (PTX) could induce ER stress and increase .the combination of METTL3/METTL14 inhibitors with PTX demonstrated a significant synergistic therapeutic effect in both BC cells and xenograft mice."	M6ADIS0065	35022519; 38582397	M6ADRUG0089
M6ACROT02274	REG00006	M6ATAR00410	DNA methylation	EPIREG00028	EPITAR00195	.	.	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"lncRNA UCA1 recruited DNA methyltransferase (DNMT1, DNMT3A, and DNMT3B) to the METTL14 promoter region to inhibit METTL14 expression in breast cancer. METTL3/METTL14 increased ER-phagy machinery formation by promoting m6A modification of the ER-phagy regulators CALCOCO1 and Sequestosome-1 (SQSTM1), thus enhancing their mRNA stability. The chemotherapeutic drug paclitaxel (PTX) could induce ER stress and increase .the combination of METTL3/METTL14 inhibitors with PTX demonstrated a significant synergistic therapeutic effect in both BC cells and xenograft mice."	M6ADIS0065	35022519; 38582397	M6ADRUG0089
M6ACROT02275	REG00009	M6ATAR00871	DNA methylation	.	EPITAR00196	.	.	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"hese data indicated that hsa-miR-550-1 might mediate a decrease in m6A levels via targeting WTAP, which led to a further reduction in WWTR1 stability. Using gain- and loss-of-function approaches, we were able to determine that miR-550-1 disrupted the proliferation and tumorigenesis of AML cells at least in part via the direct targeting of WWTR1. Chidamide treatment suppressed WT1-associated protein (WTAP)-mediated RNA m6A modification of GNAS antisense RNA 1 (GNAS-AS1). Chidamide downregulated GNAS-AS1 to inhibit glycolysis in AML cells. GNAS-AS1 targeted miR-34a-5p to promote insulin-like growth factor 2 mRNA-binding protein (IGF2BP2) expression. IGF2BP2 inhibition reversed the promoting effect of miR-34a-5p knockdown on glycolysis and RhoA/ROCK pathway in Chidamide-treated cells. GNAS-AS1 overexpression abolished the inhibitory effect of Chidamide on AML tumorigenesis in vivo by modulating the RhoA/ROCK pathway."	M6ADIS0046	33061801; 37926762	M6ADRUG0174
M6ACROT02276	REG00005	M6ATAR00443	DNA methylation	.	EPITAR00183	.	Up regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"Folic acid reduces the expression of m6A demethylase AlkB homolog 5 (ALKHB5) via promoter DNA hypermethylation. Decreased ALKBH5 causes increased m6A modification and increased expression of ATG12 in a demethylase activity-dependent manner, thereby promoting autophagy and preventing hepatic steatosis.Chlorogenic acid (CGA) is a naturally occurring plant component with the purpose of alleviating hepatic lipid deposition biological activities.CGA specifically binds to ALKBH5 and inhibits its m6A methylase activity. The inhibition of ALKBH5 activity significantly reduces Tyrosine-protein kinase receptor UFO (AXL) mRNA stability in liver cells. The AXL downregulation resulted in suppressing ERK signaling pathway activation. Overall, this study demonstrates that CGA can alleviate hepatic steatosis by regulating autophagy through the inhibition of ALKBH5 activity inhibition."	M6ADIS0107	39993647; 37805933	M6ADRUG0173
M6ACROT05854	REG00007	M6ATAR00249	DNA methylation	EPIREG00027	EPITAR00027	.	Up regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"Methyltransferase-like 3 (METTL3) increased the pri-Let-7b, decreased both the pre-Let-7b and mature Let-7b, attenuating the Let-7b controlling of stem cell renewal. The addition of Metformin increased the bindings of DNA methyltransferase-3a/b (DNMT3A/DNMT3B) to the METTL3 promoter. With the help of the readers of NKAP and HNRNPA2B1, the cluster mediated m6A formation on pri-Let-7b processing increased the mature Let-7b, the key player in suppressing Notch signaling and re-captivating Osimertinib treatment. 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	35070958; 32373962	M6ADRUG0211
M6ACROT05855	REG00007	M6ATAR00325	DNA methylation	EPIREG00027	EPITAR00027	.	Up regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"Methyltransferase-like 3 (METTL3) increased the pri-Let-7b, decreased both the pre-Let-7b and mature Let-7b, attenuating the Let-7b controlling of stem cell renewal. The addition of Metformin increased the bindings of DNA methyltransferase-3a/b (DNMT3A/DNMT3B) to the METTL3 promoter. With the help of the readers of NKAP and HNRNPA2B1, the cluster mediated m6A formation on pri-Let-7b processing increased the mature Let-7b, the key player in suppressing Notch signaling and re-captivating Osimertinib treatment. 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	35070958; 33491264	M6ADRUG0030
M6ACROT05856	REG00007	M6ATAR00249	DNA methylation	EPIREG00029	EPITAR00027	.	Up regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"Methyltransferase-like 3 (METTL3) increased the pri-Let-7b, decreased both the pre-Let-7b and mature Let-7b, attenuating the Let-7b controlling of stem cell renewal. The addition of Metformin increased the bindings of DNA methyltransferase-3a/b (DNMT3A/DNMT3B) to the METTL3 promoter. With the help of the readers of NKAP and HNRNPA2B1, the cluster mediated m6A formation on pri-Let-7b processing increased the mature Let-7b, the key player in suppressing Notch signaling and re-captivating Osimertinib treatment. 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	35070958; 32373962	M6ADRUG0211
M6ACROT05857	REG00007	M6ATAR00325	DNA methylation	EPIREG00029	EPITAR00027	.	Up regulation	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"Methyltransferase-like 3 (METTL3) increased the pri-Let-7b, decreased both the pre-Let-7b and mature Let-7b, attenuating the Let-7b controlling of stem cell renewal. The addition of Metformin increased the bindings of DNA methyltransferase-3a/b (DNMT3A/DNMT3B) to the METTL3 promoter. With the help of the readers of NKAP and HNRNPA2B1, the cluster mediated m6A formation on pri-Let-7b processing increased the mature Let-7b, the key player in suppressing Notch signaling and re-captivating Osimertinib treatment. 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	35070958; 33491264	M6ADRUG0030
M6ACROT05864	REG00012	M6ATAR00341	DNA methylation	EPIREG00027	EPITAR00515	.	Up regulation	DNA methylation	Indirect	Inhibition	m6A	DNA methylation indirectly regulates m6A modification through downstream signaling pathways	"Mechanistically, the DNA methylation of Long intergenic non-protein coding RNA 261 (LINC00261) promoter by DNMT3A, DNMT3B, and DNMT1 can upregulate the expression of LINC00261. LINC00261 recruits IGF2BP1, thereby inhibiting the stabilization of Myc proto-oncogene protein (MYC) by IGF2BP1."	M6ADIS0061	33122827	.
M6ACROT05865	REG00012	M6ATAR00341	DNA methylation	EPIREG00029	EPITAR00515	.	Up regulation	DNA methylation	Indirect	Inhibition	m6A	DNA methylation indirectly regulates m6A modification through downstream signaling pathways	"Mechanistically, the DNA methylation of Long intergenic non-protein coding RNA 261 (LINC00261) promoter by DNMT3A, DNMT3B, and DNMT1 can upregulate the expression of LINC00261. LINC00261 recruits IGF2BP1, thereby inhibiting the stabilization of Myc proto-oncogene protein (MYC) by IGF2BP1."	M6ADIS0061	33122827	.
M6ACROT05866	REG00012	M6ATAR00341	DNA methylation	EPIREG00028	EPITAR00515	.	Up regulation	DNA methylation	Indirect	Inhibition	m6A	DNA methylation indirectly regulates m6A modification through downstream signaling pathways	"Mechanistically, the DNA methylation of Long intergenic non-protein coding RNA 261 (LINC00261) promoter by DNMT3A, DNMT3B, and DNMT1 can upregulate the expression of LINC00261. LINC00261 recruits IGF2BP1, thereby inhibiting the stabilization of Myc proto-oncogene protein (MYC) by IGF2BP1."	M6ADIS0061	33122827	.
M6ACROT05975	REG00030	.	DNA methylation	EPIREG00030	EPITAR00189	.	.	DNA methylation	Indirect	Inhibition	m6A	DNA methylation indirectly regulates m6A modification through downstream signaling pathways	"Functionally, Homeobox D10 (HOXD10) acts as a tumor suppressor gene, in which HOXD10-expressing cells showed suppressed cell proliferation, colony formation ability, and migration and invasion capacity. Mechanistically, DNMT1, DNMT3B, and MeCP2 were recruited in the HOXD10 promoter, and demethylation by 5-Aza-2'-deoxycytidine (5-Aza-CdR) treatment or MeCP2 knockdown can sufficiently induce HOXD10 expression. HOXD10regulates the expressions of miR-7 and IGFBP3 in a promoter-dependent manner. "	M6ADIS0059	34790580	M6ADRUG0005
M6ACROT05976	REG00006	M6ATAR01330	DNA methylation	EPIREG00029	EPITAR00195	.	.	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"lncRNA UCA1 recruited DNA methyltransferase (DNMT1, DNMT3A, and DNMT3B) to the METTL14 promoter region to inhibit METTL14 expression in breast cancer. METTL3/METTL14 increased ER-phagy machinery formation by promoting m6A modification of the ER-phagy regulators Calcium-binding and coiled-coil domain-containing protein 1 (CALCOCO1) and p62, thus enhancing their mRNA stability. The chemotherapeutic drug paclitaxel (PTX) could induce ER stress and increase .the combination of METTL3/METTL14 inhibitors with PTX demonstrated a significant synergistic therapeutic effect in both BC cells and xenograft mice."	M6ADIS0065	35022519; 38582397	M6ADRUG0108
M6ACROT05977	REG00006	M6ATAR00410	DNA methylation	EPIREG00029	EPITAR00195	.	.	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"lncRNA UCA1 recruited DNA methyltransferase (DNMT1, DNMT3A, and DNMT3B) to the METTL14 promoter region to inhibit METTL14 expression in breast cancer. METTL3/METTL14 increased ER-phagy machinery formation by promoting m6A modification of the ER-phagy regulators CALCOCO1 and Sequestosome-1 (SQSTM1), thus enhancing their mRNA stability. The chemotherapeutic drug paclitaxel (PTX) could induce ER stress and increase .the combination of METTL3/METTL14 inhibitors with PTX demonstrated a significant synergistic therapeutic effect in both BC cells and xenograft mice."	M6ADIS0065	35022519; 38582397	M6ADRUG0108
M6ACROT05978	REG00006	M6ATAR01330	DNA methylation	EPIREG00027	EPITAR00195	.	.	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"lncRNA UCA1 recruited DNA methyltransferase (DNMT1, DNMT3A, and DNMT3B) to the METTL14 promoter region to inhibit METTL14 expression in breast cancer. METTL3/METTL14 increased ER-phagy machinery formation by promoting m6A modification of the ER-phagy regulators Calcium-binding and coiled-coil domain-containing protein 1 (CALCOCO1) and p62, thus enhancing their mRNA stability. The chemotherapeutic drug paclitaxel (PTX) could induce ER stress and increase .the combination of METTL3/METTL14 inhibitors with PTX demonstrated a significant synergistic therapeutic effect in both BC cells and xenograft mice."	M6ADIS0065	35022519; 38582397	M6ADRUG0108
M6ACROT05979	REG00006	M6ATAR00410	DNA methylation	EPIREG00027	EPITAR00195	.	.	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"lncRNA UCA1 recruited DNA methyltransferase (DNMT1, DNMT3A, and DNMT3B) to the METTL14 promoter region to inhibit METTL14 expression in breast cancer. METTL3/METTL14 increased ER-phagy machinery formation by promoting m6A modification of the ER-phagy regulators CALCOCO1 and Sequestosome-1 (SQSTM1), thus enhancing their mRNA stability. The chemotherapeutic drug paclitaxel (PTX) could induce ER stress and increase .the combination of METTL3/METTL14 inhibitors with PTX demonstrated a significant synergistic therapeutic effect in both BC cells and xenograft mice."	M6ADIS0065	35022519; 38582397	M6ADRUG0108
M6ACROT05980	REG00006	M6ATAR01330	DNA methylation	EPIREG00028	EPITAR00195	.	.	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"lncRNA UCA1 recruited DNA methyltransferase (DNMT1, DNMT3A, and DNMT3B) to the METTL14 promoter region to inhibit METTL14 expression in breast cancer. METTL3/METTL14 increased ER-phagy machinery formation by promoting m6A modification of the ER-phagy regulators Calcium-binding and coiled-coil domain-containing protein 1 (CALCOCO1) and p62, thus enhancing their mRNA stability. The chemotherapeutic drug paclitaxel (PTX) could induce ER stress and increase .the combination of METTL3/METTL14 inhibitors with PTX demonstrated a significant synergistic therapeutic effect in both BC cells and xenograft mice."	M6ADIS0065	35022519; 38582397	M6ADRUG0108
M6ACROT05981	REG00006	M6ATAR00410	DNA methylation	EPIREG00028	EPITAR00195	.	.	DNA methylation	Direct	Inhibition	m6A	DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator 	"lncRNA UCA1 recruited DNA methyltransferase (DNMT1, DNMT3A, and DNMT3B) to the METTL14 promoter region to inhibit METTL14 expression in breast cancer. METTL3/METTL14 increased ER-phagy machinery formation by promoting m6A modification of the ER-phagy regulators CALCOCO1 and Sequestosome-1 (SQSTM1), thus enhancing their mRNA stability. The chemotherapeutic drug paclitaxel (PTX) could induce ER stress and increase .the combination of METTL3/METTL14 inhibitors with PTX demonstrated a significant synergistic therapeutic effect in both BC cells and xenograft mice."	M6ADIS0065	35022519; 38582397	M6ADRUG0108
M6ACROT06003	REG00007	M6ATAR01840	DNA methylation	EPIREG00020	EPITAR00529	.	.	m6A	Indirect	Enhancement	DNA methylation	m6A modification indirectly regulates DNA methylation through downstream signaling pathways	"Here, we show that METTL3-mediated RNA N6-methyladenosine (m6A) formation leads to DNA demethylation in nearby genomic loci in normal and cancer cells, which is mediated by the interaction between m6A reader FXR1 and DNA 5-methylcytosine dioxygenase TET1. Upon recognizing RNA m6A, FXR1 recruits TET1 to genomic loci to demethylate DNA, leading to reprogrammed chromatin accessibility and gene transcription. These gene include SATB2, Ribose-5-phosphate isomerase (RPIA), WNT7B, BCL6, FAT4 and SAMD9L."	M6ADIS0056	36071173	.
M6ACROT06004	REG00051	M6ATAR01840	DNA methylation	EPIREG00020	EPITAR00529	.	.	m6A	Direct	Enhancement	DNA methylation	m6A modification directly impacts DNA methylation through recruiting DNA methyltransferases or demethylases. 	"Here, we show that METTL3-mediated RNA N6-methyladenosine (m6A) formation leads to DNA demethylation in nearby genomic loci in normal and cancer cells, which is mediated by the interaction between m6A reader FXR1 and DNA 5-methylcytosine dioxygenase TET1. Upon recognizing RNA m6A, FXR1 recruits TET1 to genomic loci to demethylate DNA, leading to reprogrammed chromatin accessibility and gene transcription. These gene include SATB2, Ribose-5-phosphate isomerase (RPIA), WNT7B, BCL6, FAT4 and SAMD9L."	M6ADIS0056	36071173	.
M6ACROT06005	REG00007	M6ATAR01843	DNA methylation	EPIREG00020	EPITAR00535	.	.	m6A	Indirect	Enhancement	DNA methylation	m6A modification indirectly regulates DNA methylation through downstream signaling pathways	"Here, we show that METTL3-mediated RNA N6-methyladenosine (m6A) formation leads to DNA demethylation in nearby genomic loci in normal and cancer cells, which is mediated by the interaction between m6A reader FXR1 and DNA 5-methylcytosine dioxygenase TET1. Upon recognizing RNA m6A, FXR1 recruits TET1 to genomic loci to demethylate DNA, leading to reprogrammed chromatin accessibility and gene transcription. These gene include SATB2, RPIA, Wnt family member 7B (WNT7B), BCL6, FAT4 and SAMD9L."	M6ADIS0056	36071173	.
M6ACROT06006	REG00051	M6ATAR01843	DNA methylation	EPIREG00020	EPITAR00535	.	.	m6A	Direct	Enhancement	DNA methylation	m6A modification directly impacts DNA methylation through recruiting DNA methyltransferases or demethylases. 	"Here, we show that METTL3-mediated RNA N6-methyladenosine (m6A) formation leads to DNA demethylation in nearby genomic loci in normal and cancer cells, which is mediated by the interaction between m6A reader FXR1 and DNA 5-methylcytosine dioxygenase TET1. Upon recognizing RNA m6A, FXR1 recruits TET1 to genomic loci to demethylate DNA, leading to reprogrammed chromatin accessibility and gene transcription. These gene include SATB2, RPIA, Wnt family member 7B (WNT7B), BCL6, FAT4 and SAMD9L."	M6ADIS0056	36071173	.
M6ACROT06007	REG00007	M6ATAR01835	DNA methylation	EPIREG00020	EPITAR00503	.	.	m6A	Indirect	Enhancement	DNA methylation	m6A modification indirectly regulates DNA methylation through downstream signaling pathways	"Here, we show that METTL3-mediated RNA N6-methyladenosine (m6A) formation leads to DNA demethylation in nearby genomic loci in normal and cancer cells, which is mediated by the interaction between m6A reader FXR1 and DNA 5-methylcytosine dioxygenase TET1. Upon recognizing RNA m6A, FXR1 recruits TET1 to genomic loci to demethylate DNA, leading to reprogrammed chromatin accessibility and gene transcription. These gene include SATB2, RPIA, WNT7B, B-cell lymphoma 6 protein (BCL6), FAT4 and SAMD9L."	M6ADIS0056	36071173	.
M6ACROT06008	REG00051	M6ATAR01835	DNA methylation	EPIREG00020	EPITAR00503	.	.	m6A	Direct	Enhancement	DNA methylation	m6A modification directly impacts DNA methylation through recruiting DNA methyltransferases or demethylases. 	"Here, we show that METTL3-mediated RNA N6-methyladenosine (m6A) formation leads to DNA demethylation in nearby genomic loci in normal and cancer cells, which is mediated by the interaction between m6A reader FXR1 and DNA 5-methylcytosine dioxygenase TET1. Upon recognizing RNA m6A, FXR1 recruits TET1 to genomic loci to demethylate DNA, leading to reprogrammed chromatin accessibility and gene transcription. These gene include SATB2, RPIA, WNT7B, B-cell lymphoma 6 protein (BCL6), FAT4 and SAMD9L."	M6ADIS0056	36071173	.
M6ACROT06009	REG00007	M6ATAR00619	DNA methylation	EPIREG00020	EPITAR00508	.	.	m6A	Indirect	Enhancement	DNA methylation	m6A modification indirectly regulates DNA methylation through downstream signaling pathways	"Here, we show that METTL3-mediated RNA N6-methyladenosine (m6A) formation leads to DNA demethylation in nearby genomic loci in normal and cancer cells, which is mediated by the interaction between m6A reader FXR1 and DNA 5-methylcytosine dioxygenase TET1. Upon recognizing RNA m6A, FXR1 recruits TET1 to genomic loci to demethylate DNA, leading to reprogrammed chromatin accessibility and gene transcription. These gene include SATB2, RPIA, WNT7B, BCL6, Protocadherin Fat 4 (FAT4) and SAMD9L."	M6ADIS0056	36071173	.
M6ACROT06010	REG00051	M6ATAR00619	DNA methylation	EPIREG00020	EPITAR00508	.	.	m6A	Direct	Enhancement	DNA methylation	m6A modification directly impacts DNA methylation through recruiting DNA methyltransferases or demethylases. 	"Here, we show that METTL3-mediated RNA N6-methyladenosine (m6A) formation leads to DNA demethylation in nearby genomic loci in normal and cancer cells, which is mediated by the interaction between m6A reader FXR1 and DNA 5-methylcytosine dioxygenase TET1. Upon recognizing RNA m6A, FXR1 recruits TET1 to genomic loci to demethylate DNA, leading to reprogrammed chromatin accessibility and gene transcription. These gene include SATB2, RPIA, WNT7B, BCL6, Protocadherin Fat 4 (FAT4) and SAMD9L."	M6ADIS0056	36071173	.
M6ACROT06011	REG00007	M6ATAR01841	DNA methylation	EPIREG00020	EPITAR00530	.	.	m6A	Indirect	Enhancement	DNA methylation	m6A modification indirectly regulates DNA methylation through downstream signaling pathways	"Here, we show that METTL3-mediated RNA N6-methyladenosine (m6A) formation leads to DNA demethylation in nearby genomic loci in normal and cancer cells, which is mediated by the interaction between m6A reader FXR1 and DNA 5-methylcytosine dioxygenase TET1. Upon recognizing RNA m6A, FXR1 recruits TET1 to genomic loci to demethylate DNA, leading to reprogrammed chromatin accessibility and gene transcription. These gene include SATB2, RPIA, WNT7B, BCL6, FAT4 and Sterile alpha motif domain-containing protein 9-like (SAMD9L)."	M6ADIS0056	36071173	.
M6ACROT06012	REG00051	M6ATAR01841	DNA methylation	EPIREG00020	EPITAR00530	.	.	m6A	Direct	Enhancement	DNA methylation	m6A modification directly impacts DNA methylation through recruiting DNA methyltransferases or demethylases. 	"Here, we show that METTL3-mediated RNA N6-methyladenosine (m6A) formation leads to DNA demethylation in nearby genomic loci in normal and cancer cells, which is mediated by the interaction between m6A reader FXR1 and DNA 5-methylcytosine dioxygenase TET1. Upon recognizing RNA m6A, FXR1 recruits TET1 to genomic loci to demethylate DNA, leading to reprogrammed chromatin accessibility and gene transcription. These gene include SATB2, RPIA, WNT7B, BCL6, FAT4 and Sterile alpha motif domain-containing protein 9-like (SAMD9L)."	M6ADIS0056	36071173	.
M6ACROT06013	REG00007	M6ATAR01569	DNA methylation	EPIREG00028	EPITAR00506	.	Down regulation	m6A	Direct	Enhancement	DNA methylation	m6A modification directly impacts DNA methylation through recruiting DNA methyltransferases or demethylases.	"METTL3-METTL14 recruits the DNA methyltransferase DNMT1 to chromatin for gene-body methylation including Notch2, DNA (cytosine-5)-methyltransferase 1 (DNMT1), Insr and Smad3, whose expression is fine-tuned by both gene-body 5mC, which promotes transcription, and m6A, which destabilizes transcripts. We demonstrate that METTL3-METTL14-dependent 5mC and m6A are both essential for the differentiation of embryonic stem cells into embryoid bodies and that the upregulation of key differentiation genes during early differentiation depends on the dynamic balance between increased 5mC and decreased m6A."	.	39826545	.
M6ACROT06014	REG00006	M6ATAR01569	DNA methylation	EPIREG00028	EPITAR00506	.	Down regulation	m6A	Direct	Enhancement	DNA methylation	m6A modification directly impacts DNA methylation through recruiting DNA methyltransferases or demethylases.	"METTL3-METTL14 recruits the DNA methyltransferase DNMT1 to chromatin for gene-body methylation including Notch2, DNA (cytosine-5)-methyltransferase 1 (DNMT1), Insr and Smad3, whose expression is fine-tuned by both gene-body 5mC, which promotes transcription, and m6A, which destabilizes transcripts. We demonstrate that METTL3-METTL14-dependent 5mC and m6A are both essential for the differentiation of embryonic stem cells into embryoid bodies and that the upregulation of key differentiation genes during early differentiation depends on the dynamic balance between increased 5mC and decreased m6A."	.	39826545	.
M6ACROT06015	REG00007	M6ATAR00558	DNA methylation	EPIREG00028	EPITAR00513	.	Down regulation	m6A	Direct	Enhancement	DNA methylation	m6A modification directly impacts DNA methylation through recruiting DNA methyltransferases or demethylases.	"METTL3-METTL14 recruits the DNA methyltransferase DNMT1 to chromatin for gene-body methylation including Notch2, Eomes, Insulin receptor (INSR) and Smad3, whose expression is fine-tuned by both gene-body 5mC, which promotes transcription, and m6A, which destabilizes transcripts. We demonstrate that METTL3-METTL14-dependent 5mC and m6A are both essential for the differentiation of embryonic stem cells into embryoid bodies and that the upregulation of key differentiation genes during early differentiation depends on the dynamic balance between increased 5mC and decreased m6A."	.	39826545	.
M6ACROT06016	REG00006	M6ATAR00558	DNA methylation	EPIREG00028	EPITAR00513	.	Down regulation	m6A	Direct	Enhancement	DNA methylation	m6A modification directly impacts DNA methylation through recruiting DNA methyltransferases or demethylases.	"METTL3-METTL14 recruits the DNA methyltransferase DNMT1 to chromatin for gene-body methylation including Notch2, Eomes, Insulin receptor (INSR) and Smad3, whose expression is fine-tuned by both gene-body 5mC, which promotes transcription, and m6A, which destabilizes transcripts. We demonstrate that METTL3-METTL14-dependent 5mC and m6A are both essential for the differentiation of embryonic stem cells into embryoid bodies and that the upregulation of key differentiation genes during early differentiation depends on the dynamic balance between increased 5mC and decreased m6A."	.	39826545	.
M6ACROT06017	REG00007	M6ATAR00396	DNA methylation	EPIREG00028	EPITAR00438	.	Down regulation	m6A	Direct	Enhancement	DNA methylation	m6A modification directly impacts DNA methylation through recruiting DNA methyltransferases or demethylases.	"METTL3-METTL14 recruits the DNA methyltransferase DNMT1 to chromatin for gene-body methylation including Notch2, Eomes, Insr and Mothers against decapentaplegic homolog 3 (SMAD3), whose expression is fine-tuned by both gene-body 5mC, which promotes transcription, and m6A, which destabilizes transcripts. We demonstrate that METTL3-METTL14-dependent 5mC and m6A are both essential for the differentiation of embryonic stem cells into embryoid bodies and that the upregulation of key differentiation genes during early differentiation depends on the dynamic balance between increased 5mC and decreased m6A."	.	39826545	.
M6ACROT06018	REG00006	M6ATAR00396	DNA methylation	EPIREG00028	EPITAR00438	.	Down regulation	m6A	Direct	Enhancement	DNA methylation	m6A modification directly impacts DNA methylation through recruiting DNA methyltransferases or demethylases.	"METTL3-METTL14 recruits the DNA methyltransferase DNMT1 to chromatin for gene-body methylation including Notch2, Eomes, Insr and Mothers against decapentaplegic homolog 3 (SMAD3), whose expression is fine-tuned by both gene-body 5mC, which promotes transcription, and m6A, which destabilizes transcripts. We demonstrate that METTL3-METTL14-dependent 5mC and m6A are both essential for the differentiation of embryonic stem cells into embryoid bodies and that the upregulation of key differentiation genes during early differentiation depends on the dynamic balance between increased 5mC and decreased m6A."	.	39826545	.