m6A Target Gene Information

General Information of the m6A Target Gene (ID: M6ATAR00141)
Target Name Metastasis associated lung adenocarcinoma transcript 1 (MALAT1)
Synonyms
MALAT1; metastasis associated lung adenocarcinoma transcript 1 (non-protein coding); PRO1073; MALAT-1; NCRNA00047; HCN; NEAT2; LINC00047; mascRNA; metastasis associated in lung adenocarcinoma transcript 1; non-protein coding RNA 47; hepcarcin; nuclear enriched abundant transcript 2; nuclear paraspeckle assembly transcript 2 (non-protein coding); long intergenic non-protein coding RNA 47
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Gene Name MALAT1
Chromosomal Location 11q13.1
Family Long non-coding RNAs with non-systematic symbols
Gene ID 378938
HGNC ID
HGNC:29665
Ensembl Gene ID
ENSG00000251562
Full List of m6A Methylation Regulator of This Target Gene and Corresponding Disease/Drug Response(s)
MALAT1 can be regulated by the following regulator(s), and cause disease/drug response(s). You can browse detail information of regulator(s) or disease/drug response(s).
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Methyltransferase-like 3 (METTL3) [WRITER]
 Regulator Info 
Representative RNA-seq result indicating the expression of this target gene regulated by METTL3
Cell Line DKO-1 cell line Homo sapiens
Treatment: METTL3 knockdown DKO-1 cell
Control: DKO-1 cell
 GSE182382
Regulation
logFC: 8.20E-01
p-value: 5.93E-03
More Results Click to View More RNA-seq Results
Representative RIP-seq result supporting the interaction between MALAT1 and the regulator
Cell Line MDA-MB-231 Homo sapiens
Regulation logFC: 1.28E+00 GSE60213
In total 9 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [1]
Response Summary METTL3 promoted the malignant progression of IDH-wildtype gliomas and revealed important insight into the upstream regulatory mechanism of Metastasis associated lung adenocarcinoma transcript 1 (MALAT1) and NF-Kappa-B with a primary focus on m6A modification.
Target Regulation Up regulation
Responsed Disease Glioma ICD-11: 2A00.0
 Disease Info 
Pathway Response TNF signaling pathway hsa04668
Cell Process Cell proliferation and metastasis
In-vitro Model H4 Astrocytoma Homo sapiens CVCL_1239
LN-229 Glioblastoma Homo sapiens CVCL_0393
U87 (A primary glioblastoma cell line)
In-vivo Model U87 cells (5 × 105) transfected with an empty vector, METTL3 shRNA, or METTL3 overexpression vector were inoculated into the right frontal node of nude mice.
Experiment 2 Reporting the m6A Methylation Regulator of This Target Gene [2]
Response Summary METTL3, YTHDF3, YTHDF1, and eIF3b directly promoted YAP translation through an interaction with the translation initiation machinery. METTL3 knockdown inhibits tumor growth and enhances sensitivity to DDP in vivo.m6A mRNA methylation initiated by METTL3 directly promotes YAP translation and increases YAP activity by regulating the Metastasis associated lung adenocarcinoma transcript 1 (MALAT1)-miR-1914-3p-YAP axis to induce Non-small cell lung cancer drug resistance and metastasis.
Target Regulation Up regulation
Responsed Disease Non-small-cell lung carcinoma ICD-11: 2C25.Y
 Disease Info 
Responsed Drug Cisplatin Approved
 Drug Info 
Pathway Response Hippo signaling pathway hsa04390
Cell Process Metabolic
In-vitro Model A-549 Lung adenocarcinoma Homo sapiens CVCL_0023
Calu-6 Lung adenocarcinoma Homo sapiens CVCL_0236
NCI-H1299 Lung large cell carcinoma Homo sapiens CVCL_0060
NCI-H520 Lung squamous cell carcinoma Homo sapiens CVCL_1566
In-vivo Model Mice were injected with 5 × 106 lung cancer cells with stably expression of relevant plasmids and randomly divided into two groups (five mice per group) after the diameter of the xenografted tumors had reached approximately 5 mm in diameter. Xenografted mice were then administrated with PBS or DDP (3 mg/kg per day) for three times a week, and tumor volume were measured every second day.
Experiment 3 Reporting the m6A Methylation Regulator of This Target Gene [3]
Response Summary This study highlighted METTL3 as a tumor promoter in Thymic tumors and c-MYC as a promising target to be exploited for the treatment of TET. High expression of c-MYC protein is enabled by lncRNA Metastasis associated lung adenocarcinoma transcript 1 (MALAT1), which is methylated and delocalized by METTL3. Silencing of METTL3 combined with cisplatin or c-MYC inhibitor induces cell death in TET cells. Blocking of c-MYC by using JQ1 inhibitor cooperates with METTL3 depletion in the inhibition of proliferation and induction of cell death.
Target Regulation Up regulation
Responsed Disease Thymic epithelial tumors ICD-11: 2C27.Y
 Disease Info 
Responsed Drug Cisplatin Approved
 Drug Info 
Pathway Response Cellular senescence hsa04218
Cell Process Cell viability and proliferation
In-vitro Model T1889 Thymic undifferentiated carcinoma Homo sapiens CVCL_D024
Experiment 4 Reporting the m6A Methylation Regulator of This Target Gene [3]
Response Summary This study highlighted METTL3 as a tumor promoter in Thymic tumors and c-MYC as a promising target to be exploited for the treatment of TET. High expression of c-MYC protein is enabled by lncRNA Metastasis associated lung adenocarcinoma transcript 1 (MALAT1), which is methylated and delocalized by METTL3. Silencing of METTL3 combined with cisplatin or c-MYC inhibitor induces cell death in TET cells. Blocking of c-MYC by using JQ1 inhibitor cooperates with METTL3 depletion in the inhibition of proliferation and induction of cell death.
Target Regulation Up regulation
Responsed Disease Thymic epithelial tumors ICD-11: 2C27.Y
 Disease Info 
Responsed Drug JQ-1 Phase 1
 Drug Info 
Pathway Response Cellular senescence hsa04218
Cell Process Cell viability and proliferation
In-vitro Model T1889 Thymic undifferentiated carcinoma Homo sapiens CVCL_D024
Experiment 5 Reporting the m6A Methylation Regulator of This Target Gene [4]
Response Summary METTL3 can regulate the expression of Metastasis associated lung adenocarcinoma transcript 1 (MALAT1) through m6A, mediate the E2F1/AGR2 axis, and promote the adriamycin resistance of breast cancer.
Target Regulation Up regulation
Responsed Disease Breast cancer ICD-11: 2C60
 Disease Info 
Responsed Drug Doxil Approved
 Drug Info 
In-vitro Model MCF7-DoxR (Adriamycin-resistant cell line MCF7-DoxR)
MCF-7 Invasive breast carcinoma Homo sapiens CVCL_0031
In-vivo Model Once the tumor volume increased to about 1 cm3, six groups of MCF7 bearing mice (n = 10 in each group) were injected with PBS (0.1 ml, caudal vein) and adriamycin (0.1 ml, 10 mg/kg), respectively. When the tumor reached 1.5 cm in any direction (defined as event-free survival analysis), 10 mice in each group were selected to measure the tumor size and weight on the 12th day after adriamycin injection.
Experiment 6 Reporting the m6A Methylation Regulator of This Target Gene [5]
Response Summary Silencing METTL3 down-regulate Metastasis associated lung adenocarcinoma transcript 1 (MALAT1) and HMGA2 by sponging miR-26b, and finally inhibit EMT, migration and invasion in breast cancer, providing a theoretical basis for clinical treatment of breast cancer.
Target Regulation Up regulation
Responsed Disease Breast cancer ICD-11: 2C60
 Disease Info 
Cell Process Epithelial-mesenchymal transition
In-vitro Model MCF-7 Invasive breast carcinoma Homo sapiens CVCL_0031
MDA-MB-231 Breast adenocarcinoma Homo sapiens CVCL_0062
MDA-MB-468 Breast adenocarcinoma Homo sapiens CVCL_0419
MCF-10A Normal Homo sapiens CVCL_0598
Experiment 7 Reporting the m6A Methylation Regulator of This Target Gene [5]
Response Summary Silencing METTL3 down-regulate Metastasis associated lung adenocarcinoma transcript 1 (MALAT1) and HMGA2 by sponging miR-26b, and finally inhibit EMT, migration and invasion in BC, providing a theoretical basis for clinical treatment of BC.
Target Regulation Up regulation
Responsed Disease Breast cancer ICD-11: 2C60
 Disease Info 
Cell Process Epithelial-mesenchymal transition
In-vitro Model MDA-MB-468 Breast adenocarcinoma Homo sapiens CVCL_0419
MDA-MB-231 Breast adenocarcinoma Homo sapiens CVCL_0062
MCF-7 Invasive breast carcinoma Homo sapiens CVCL_0031
MCF-10A Normal Homo sapiens CVCL_0598
In-vivo Model Eighteen BALB/C female nude mice aged 4-5 weeks and weighing 15-18 g were randomly assigned into three groups of six mice. The MCF-7 cell lines stably transfected with sh-NC + oe-NC, sh-METTL3 + oe-NC and sh-METTL3 + oe-HMGA2 were selected for subcutaneous establishment of the BC cell line MCF-7 as xenografts in the nude mice. For this purpose, MCF-7 cell lines in the logarithmic growth stage were prepared into a suspension with a concentration of about 1 × 107 cells/ml. The prepared cell suspension was injected into the left armpit of the mice, and the subsequent tumor growth was recorded.
Experiment 8 Reporting the m6A Methylation Regulator of This Target Gene [6]
Response Summary Renal fibrosis is a key factor in chronic kidney disease (CKD). Metastasis associated lung adenocarcinoma transcript 1 (MALAT1)/miR-145/FAK pathway was involved in the effect of dihydroartemisinin (DHA) on TGF-beta1-induced renal fibrosis in vitro and in vivo.
Responsed Disease Chronic kidney disease ICD-11: GB61
 Disease Info 
Responsed Drug Artenimol Approved
 Drug Info 
Cell Process Epithelial-mesenchymal transition
In-vitro Model HK-2 [Human kidney] Normal Homo sapiens CVCL_0302
HK2 Normal Acipenser baerii CVCL_YE28
In-vivo Model For the unilateral ureteral obstruction (UUO) model, male C57BL/6J mice at 8 weeks of age (20-22 g body weight) were first anaesthetized with pentobarbital sodium (50 mg/kg) via intraperitoneal injection. Then, the left ureter was ligated using 3-0 silk and a left lateral incision.
Experiment 9 Reporting the m6A Methylation Regulator of This Target Gene [7]
Response Summary m6A modification is co-regulated by METTL3 and FTO in cadmium-treated cells. Metastasis associated lung adenocarcinoma transcript 1 (MALAT1), LncRNA-PVT1 and m6A modification could be key nodes for cadmium-induced oxidative damage, and highlight their importance as promising preventive and therapeutic targets in cadmium toxicity.
Target Regulation Up regulation
Responsed Disease Kidney failure ICD-11: GB6Z
 Disease Info 
In-vitro Model NIT-1 Insulin tumor Mus musculus CVCL_3561
Fat mass and obesity-associated protein (FTO) [ERASER]
 Regulator Info 
Representative RNA-seq result indicating the expression of this target gene regulated by FTO
Cell Line NB4 cell line Homo sapiens
Treatment: shFTO NB4 cells
Control: shNS NB4 cells
 GSE103494
Regulation
logFC: 8.67E-01
p-value: 5.83E-03
More Results Click to View More RNA-seq Results
In total 3 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [8]
Response Summary In bladder cancer, the changes in m6A methylation level mainly appeared at 5' untranslated region (5' UTR) of Metastasis associated lung adenocarcinoma transcript 1 (MALAT1) and NOTCH1 transcripts, and at 3' UTR of CSNK2A2 and ITGA6 transcripts, responding to the overexpression of FTO. SFPQ could influence the FTO-mediated m6A RNA demethylation, eventually affecting the gene expression.
Target Regulation Down regulation
Responsed Disease Bladder cancer ICD-11: 2C94
 Disease Info 
Pathway Response Notch signaling pathway hsa04330
Cell Process Cell proliferation
Cell invasion
Cell apoptosis
In-vitro Model HT-1197 Recurrent bladder carcinoma Homo sapiens CVCL_1291
HT-1376 Bladder carcinoma Homo sapiens CVCL_1292
In-vivo Model BALB/cnu/nu mice (4-5 weeks old) were used for the xenograft experiment. The mice were randomly divided into 2 groups (n = 6 for each group) and injected with 5 × 106 HT-1197 cells in control group or FTO plasmid group, respectively.
Experiment 2 Reporting the m6A Methylation Regulator of This Target Gene [9]
Response Summary FTO facilitates the tumorigenesis of bladder cancer through regulating the Metastasis associated lung adenocarcinoma transcript 1 (MALAT1)/miR-384/MAL2 axis in m6A RNA modification manner, which ensures the potential of FTO for serving as a diagnostic or prognostic biomarker in bladder cancer.
Target Regulation Up regulation
Responsed Disease Bladder cancer ICD-11: 2C94
 Disease Info 
Cell Process RNA stability
In-vitro Model T24 Bladder carcinoma Homo sapiens CVCL_0554
SV-HUC-1 Normal Homo sapiens CVCL_3798
SCaBER Bladder squamous cell carcinoma Homo sapiens CVCL_3599
J82 Bladder carcinoma Homo sapiens CVCL_0359
253J Bladder carcinoma Homo sapiens CVCL_7935
5637 Bladder carcinoma Homo sapiens CVCL_0126
In-vivo Model Approximately 5 × 106 253J and 5637 cells infected with indicated vectors were injected subcutaneously into the flank of the mice.
Experiment 3 Reporting the m6A Methylation Regulator of This Target Gene [7]
Response Summary m6A modification is co-regulated by METTL3 and FTO in cadmium-treated cells. Metastasis associated lung adenocarcinoma transcript 1 (MALAT1), LncRNA-PVT1 and m6A modification could be key nodes for cadmium-induced oxidative damage, and highlight their importance as promising preventive and therapeutic targets in cadmium toxicity.
Target Regulation Up regulation
Responsed Disease Kidney failure ICD-11: GB6Z
 Disease Info 
In-vitro Model NIT-1 Insulin tumor Mus musculus CVCL_3561
RNA binding protein X (RBMX) [READER]
 Regulator Info 
Representative RNA-seq result indicating the expression of this target gene regulated by RBMX
Cell Line HEK293 cell line Homo sapiens
Treatment: RBMX overexpressed HEK293 cells
Control: Wild type HEK293 cells
 GSE68990
Regulation
logFC: -6.91E-01
p-value: 3.81E-02
More Results Click to View More RNA-seq Results
In total 1 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [10]
Response Summary HNRNPG can bind the m6A-modified hairpin of Metastasis associated lung adenocarcinoma transcript 1 (MALAT1).
RNA demethylase ALKBH5 (ALKBH5) [ERASER]
 Regulator Info 
Representative RNA-seq result indicating the expression of this target gene regulated by ALKBH5
Cell Line NOMO-1 cell line Homo sapiens
Treatment: shALKBH5 NOMO-1 cells
Control: shNS NOMO-1 cells
 GSE144968
Regulation
logFC: 1.03E+00
p-value: 3.88E-04
More Results Click to View More RNA-seq Results
In total 1 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [11]
Response Summary ALKBH5 could up-regulate Metastasis associated lung adenocarcinoma transcript 1 (MALAT1) expression by demethylation. Furthermore, dexmedetomidine inhibited the expression of ALKBH5 in LPS-treated HK-2 cells. Dexmedetomidine suppressed the biological behavior of HK-2 cells treated with LPS by inhibiting the expression of ALKBH5 in vitro, which provides potential targets for the prevention and treatment of sepsis-induced kidney injury. Dexmedetomidine suppressed the biological behavior of HK-2 cells treated with LPS by inhibiting the expression of ALKBH5 in vitro, which provides potential targets for the prevention and treatment of sepsis-induced kidney injury.
Target Regulation Up regulation
Responsed Disease Injury of kidney ICD-11: NB92.0Z
 Disease Info 
Cell Process Cell cycle
Cell proliferation
Cell apoptosis
In-vitro Model HK2 Normal Acipenser baerii CVCL_YE28
YTH domain-containing protein 1 (YTHDC1) [READER]
 Regulator Info 
Representative RNA-seq result indicating the expression of this target gene regulated by YTHDC1
Cell Line MOLM-13 cell line Homo sapiens
Treatment: shYTHDC1 MOLM13 cells
Control: shControl MOLM13 cells
 GSE168565
Regulation
logFC: 1.45E+00
p-value: 5.75E-21
More Results Click to View More RNA-seq Results
In total 1 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [12]
Response Summary MALAT1 hijacks both chimeric mRNAs and fusion protein in nuclear speckles during chromosomal translocation and mediates colocalization with METTL14 in an oncogenic fusion protein such as PML-RARalpha. Reducing MALAT1 or m6A methyltransferases and the 'reader' YTHDC1 result in the universal retention of distinct oncogenic gene (PML-RARalpha) mRNAs in nucleus. Targeting the lncRNA-triggered autoregulatory loop to disrupt chimeric mRNA transport represents a new common paradigm for treating blood malignancies.
Target Regulation Up regulation
Responsed Disease Blood malignancies ICD-11: 2B33.Y
 Disease Info 
Cell Process Oncogenic fusion protein expression
In-vitro Model HEK293T Normal Homo sapiens CVCL_0063
HL-60 Adult acute myeloid leukemia Homo sapiens CVCL_0002
K-562 Chronic myelogenous leukemia Homo sapiens CVCL_0004
Kasumi-1 Myeloid leukemia with maturation Homo sapiens CVCL_0589
MOLM-13 Adult acute myeloid leukemia Homo sapiens CVCL_2119
NB4 Acute promyelocytic leukemia Homo sapiens CVCL_0005
In-vivo Model The NOD-SCID mice were intravenously (tail vein) implanted with sh-RNA-established NB4 cells. Direct injection of 5 × 106 shRNA-transformed NB4 cells into 150 uL of PBS was performed to establish intravenous (tail vein) leukemia.
Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) [READER]
 Regulator Info 
Representative RIP-seq result supporting the interaction between MALAT1 and the regulator
Cell Line HEK293T Homo sapiens
Regulation logFC: 1.31E+00 GSE90639
In total 1 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [13]
Response Summary IGF2BP2 promotes Metastasis associated lung adenocarcinoma transcript 1 (MALAT1) stability in an m6A-dependent mechanism, thus promoting its downstream target autophagy-related (ATG)12 expression and NSCLC proliferation.
Target Regulation Up regulation
Responsed Disease Non-small-cell lung carcinoma ICD-11: 2C25.Y
 Disease Info 
Pathway Response Lysosome hsa04142
Cell Process Cell autophagy
In-vitro Model NCI-H157 Lung squamous cell carcinoma Homo sapiens CVCL_0463
NCI-H460 Lung large cell carcinoma Homo sapiens CVCL_0459
NCI-H1975 Lung adenocarcinoma Homo sapiens CVCL_1511
NCI-H1703 Lung squamous cell carcinoma Homo sapiens CVCL_1490
NCI-H1299 Lung large cell carcinoma Homo sapiens CVCL_0060
BEAS-2B Normal Homo sapiens CVCL_0168
A-549 Lung adenocarcinoma Homo sapiens CVCL_0023
In-vivo Model Mice (male and 6 weeks old) were subcutaneously injected with NSCLC cells (1.0*106 cells/200 uL). The mice were terminated after 4 weeks of induction, and the tumor volume and tumor weight were measured.
Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) [READER]
 Regulator Info 
Representative RIP-seq result supporting the interaction between MALAT1 and the regulator
Cell Line HEK293T Homo sapiens
Regulation logFC: 2.96E+00 GSE90639
In total 1 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [14]
Response Summary circRNA hsa_circ_0004287 was upregulated in peripheral blood mononuclear cells of both AD and psoriasis patients. hsa_circ_0004287 reduced the stability of its host gene Metastasis associated lung adenocarcinoma transcript 1 (MALAT1) by competitively binding to IGF2BP3 with MALAT1 in an N6-methyladenosine (m6A)-dependent manner.
Target Regulation Up regulation
Responsed Disease Atopic eczema ICD-11: EA80
 Disease Info 
Pathway Response MAPK signaling pathway hsa04010
Ubiquitin mediated proteolysis hsa04120
Cell Process Inflammation
Proteasome pathway degradation
In-vitro Model RAW 264.7 Mouse leukemia Mus musculus CVCL_0493
In-vivo Model IMQ-induced psoriatic model was constructed by applying 10 mg per ear 5% IMQ for 8 consecutive days, and 6 ug macrophage-specific control or hsa_circ_0004287 plasmid was topically applied every 2 days (5 mice per group per experiment).
YTH domain-containing family protein 1 (YTHDF1) [READER]
 Regulator Info 
Representative RIP-seq result supporting the interaction between MALAT1 and the regulator
Cell Line Hela Homo sapiens
Regulation logFC: 2.44E+00 GSE63591
In total 1 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [2]
Response Summary METTL3, YTHDF3, YTHDF1, and eIF3b directly promoted YAP translation through an interaction with the translation initiation machinery. METTL3 knockdown inhibits tumor growth and enhances sensitivity to DDP in vivo.m6A mRNA methylation initiated by METTL3 directly promotes YAP translation and increases YAP activity by regulating the Metastasis associated lung adenocarcinoma transcript 1 (MALAT1)-miR-1914-3p-YAP axis to induce Non-small cell lung cancer drug resistance and metastasis.
Target Regulation Up regulation
Responsed Disease Non-small-cell lung carcinoma ICD-11: 2C25.Y
 Disease Info 
Responsed Drug Cisplatin Approved
 Drug Info 
Pathway Response Hippo signaling pathway hsa04390
Cell Process Metabolic
In-vitro Model A-549 Lung adenocarcinoma Homo sapiens CVCL_0023
Calu-6 Lung adenocarcinoma Homo sapiens CVCL_0236
NCI-H1299 Lung large cell carcinoma Homo sapiens CVCL_0060
NCI-H520 Lung squamous cell carcinoma Homo sapiens CVCL_1566
In-vivo Model Mice were injected with 5 × 106 lung cancer cells with stably expression of relevant plasmids and randomly divided into two groups (five mice per group) after the diameter of the xenografted tumors had reached approximately 5 mm in diameter. Xenografted mice were then administrated with PBS or DDP (3 mg/kg per day) for three times a week, and tumor volume were measured every second day.
YTH domain-containing family protein 3 (YTHDF3) [READER]
 Regulator Info 
Representative RIP-seq result supporting the interaction between MALAT1 and the regulator
Cell Line Hela Homo sapiens
Regulation logFC: 1.66E+00 GSE86214
In total 1 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [2]
Response Summary METTL3, YTHDF3, YTHDF1, and eIF3b directly promoted YAP translation through an interaction with the translation initiation machinery. METTL3 knockdown inhibits tumor growth and enhances sensitivity to DDP in vivo.m6A mRNA methylation initiated by METTL3 directly promotes YAP translation and increases YAP activity by regulating the Metastasis associated lung adenocarcinoma transcript 1 (MALAT1)-miR-1914-3p-YAP axis to induce Non-small cell lung cancer drug resistance and metastasis.
Target Regulation Up regulation
Responsed Disease Non-small-cell lung carcinoma ICD-11: 2C25.Y
 Disease Info 
Responsed Drug Cisplatin Approved
 Drug Info 
Pathway Response Hippo signaling pathway hsa04390
Cell Process Metabolic
In-vitro Model A-549 Lung adenocarcinoma Homo sapiens CVCL_0023
Calu-6 Lung adenocarcinoma Homo sapiens CVCL_0236
NCI-H1299 Lung large cell carcinoma Homo sapiens CVCL_0060
NCI-H520 Lung squamous cell carcinoma Homo sapiens CVCL_1566
In-vivo Model Mice were injected with 5 × 106 lung cancer cells with stably expression of relevant plasmids and randomly divided into two groups (five mice per group) after the diameter of the xenografted tumors had reached approximately 5 mm in diameter. Xenografted mice were then administrated with PBS or DDP (3 mg/kg per day) for three times a week, and tumor volume were measured every second day.
Methyltransferase-like 14 (METTL14) [WRITER]
 Regulator Info 
In total 2 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [12]
Response Summary MALAT1 hijacks both chimeric mRNAs and fusion protein in nuclear speckles during chromosomal translocation and mediates colocalization with METTL14 in an oncogenic fusion protein such as PML-RARalpha. Reducing MALAT1 or m6A methyltransferases and the 'reader' YTHDC1 result in the universal retention of distinct oncogenic gene (PML-RARalpha) mRNAs in nucleus. Targeting the lncRNA-triggered autoregulatory loop to disrupt chimeric mRNA transport represents a new common paradigm for treating blood malignancies.
Target Regulation Up regulation
Responsed Disease Blood malignancies ICD-11: 2B33.Y
 Disease Info 
Cell Process Oncogenic fusion protein expression
In-vitro Model HEK293T Normal Homo sapiens CVCL_0063
HL-60 Adult acute myeloid leukemia Homo sapiens CVCL_0002
K-562 Chronic myelogenous leukemia Homo sapiens CVCL_0004
Kasumi-1 Myeloid leukemia with maturation Homo sapiens CVCL_0589
MOLM-13 Adult acute myeloid leukemia Homo sapiens CVCL_2119
NB4 Acute promyelocytic leukemia Homo sapiens CVCL_0005
In-vivo Model The NOD-SCID mice were intravenously (tail vein) implanted with sh-RNA-established NB4 cells. Direct injection of 5 × 106 shRNA-transformed NB4 cells into 150 uL of PBS was performed to establish intravenous (tail vein) leukemia.
Experiment 2 Reporting the m6A Methylation Regulator of This Target Gene [15]
Response Summary METTL14 and lncRNA Metastasis associated lung adenocarcinoma transcript 1 (MALAT1) were upregulated, and miR-224-5p was downregulated in OSCC tissues and cells. METTL14 induced m6A modification of MALAT1 to upregulate MALAT1.
Target Regulation Up regulation
Responsed Disease Oral squamous cell carcinoma ICD-11: 2B6E.0
 Disease Info 
In-vitro Model SCC-25 Tongue squamous cell carcinoma Homo sapiens CVCL_1682
SCC-15 Tongue squamous cell carcinoma Homo sapiens CVCL_1681
Hs 680.Tg Normal Homo sapiens CVCL_0842
FaDu Hypopharyngeal squamous cell carcinoma Homo sapiens CVCL_1218
CAL-27 Tongue squamous cell carcinoma Homo sapiens CVCL_1107
In-vivo Model Lentiviruses containing sh-METTL-14 and its negative control (RiboBio Co., Ltd., Guangzhou, China) were transduced into CAL27 cells and stably transduced cells were screened using puromycin. CAL27 cells (3 × 106 cells/mouse) were subcutaneously inoculated into the posterior flank of each mouse (N = 12/group).
Methyltransferase-like 16 (METTL16) [WRITER]
 Regulator Info 
In total 1 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [16]
Response Summary LncRNAs are involved in a plethora of cellular signaling pathways and actively regulate gene expression via a broad selection of molecular mechanisms. Metastasis associated lung adenocarcinoma transcript 1 (MALAT1) could serve a role as a regulator of RNA processing or modification events through guiding METTL16 onto its RNA targets.
Brain cancer [ICD-11: 2A00]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [1]
Response Summary METTL3 promoted the malignant progression of IDH-wildtype gliomas and revealed important insight into the upstream regulatory mechanism of Metastasis associated lung adenocarcinoma transcript 1 (MALAT1) and NF-Kappa-B with a primary focus on m6A modification.
Responsed Disease Glioma [ICD-11: 2A00.0]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Up regulation
Pathway Response TNF signaling pathway hsa04668
Cell Process Cell proliferation and metastasis
In-vitro Model H4 Astrocytoma Homo sapiens CVCL_1239
LN-229 Glioblastoma Homo sapiens CVCL_0393
U87 (A primary glioblastoma cell line)
In-vivo Model U87 cells (5 × 105) transfected with an empty vector, METTL3 shRNA, or METTL3 overexpression vector were inoculated into the right frontal node of nude mice.
Malignant haematopoietic neoplasm [ICD-11: 2B33]
 Disease Info 
In total 2 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [12]
Response Summary MALAT1 hijacks both chimeric mRNAs and fusion protein in nuclear speckles during chromosomal translocation and mediates colocalization with METTL14 in an oncogenic fusion protein such as PML-RARalpha. Reducing MALAT1 or m6A methyltransferases and the 'reader' YTHDC1 result in the universal retention of distinct oncogenic gene (PML-RARalpha) mRNAs in nucleus. Targeting the lncRNA-triggered autoregulatory loop to disrupt chimeric mRNA transport represents a new common paradigm for treating blood malignancies.
Responsed Disease Blood malignancies [ICD-11: 2B33.Y]
Target Regulator Methyltransferase-like 14 (METTL14) WRITER
 Regulator Info 
Target Regulation Up regulation
Cell Process Oncogenic fusion protein expression
In-vitro Model HEK293T Normal Homo sapiens CVCL_0063
HL-60 Adult acute myeloid leukemia Homo sapiens CVCL_0002
K-562 Chronic myelogenous leukemia Homo sapiens CVCL_0004
Kasumi-1 Myeloid leukemia with maturation Homo sapiens CVCL_0589
MOLM-13 Adult acute myeloid leukemia Homo sapiens CVCL_2119
NB4 Acute promyelocytic leukemia Homo sapiens CVCL_0005
In-vivo Model The NOD-SCID mice were intravenously (tail vein) implanted with sh-RNA-established NB4 cells. Direct injection of 5 × 106 shRNA-transformed NB4 cells into 150 uL of PBS was performed to establish intravenous (tail vein) leukemia.
Experiment 2 Reporting the m6A-centered Disease Response [12]
Response Summary MALAT1 hijacks both chimeric mRNAs and fusion protein in nuclear speckles during chromosomal translocation and mediates colocalization with METTL14 in an oncogenic fusion protein such as PML-RARalpha. Reducing MALAT1 or m6A methyltransferases and the 'reader' YTHDC1 result in the universal retention of distinct oncogenic gene (PML-RARalpha) mRNAs in nucleus. Targeting the lncRNA-triggered autoregulatory loop to disrupt chimeric mRNA transport represents a new common paradigm for treating blood malignancies.
Responsed Disease Blood malignancies [ICD-11: 2B33.Y]
Target Regulator YTH domain-containing protein 1 (YTHDC1) READER
 Regulator Info 
Target Regulation Up regulation
Cell Process Oncogenic fusion protein expression
In-vitro Model HEK293T Normal Homo sapiens CVCL_0063
HL-60 Adult acute myeloid leukemia Homo sapiens CVCL_0002
K-562 Chronic myelogenous leukemia Homo sapiens CVCL_0004
Kasumi-1 Myeloid leukemia with maturation Homo sapiens CVCL_0589
MOLM-13 Adult acute myeloid leukemia Homo sapiens CVCL_2119
NB4 Acute promyelocytic leukemia Homo sapiens CVCL_0005
In-vivo Model The NOD-SCID mice were intravenously (tail vein) implanted with sh-RNA-established NB4 cells. Direct injection of 5 × 106 shRNA-transformed NB4 cells into 150 uL of PBS was performed to establish intravenous (tail vein) leukemia.
Head and neck squamous carcinoma [ICD-11: 2B6E]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [15]
Response Summary METTL14 and lncRNA Metastasis associated lung adenocarcinoma transcript 1 (MALAT1) were upregulated, and miR-224-5p was downregulated in OSCC tissues and cells. METTL14 induced m6A modification of MALAT1 to upregulate MALAT1.
Responsed Disease Oral squamous cell carcinoma [ICD-11: 2B6E.0]
Target Regulator Methyltransferase-like 14 (METTL14) WRITER
 Regulator Info 
Target Regulation Up regulation
In-vitro Model SCC-25 Tongue squamous cell carcinoma Homo sapiens CVCL_1682
SCC-15 Tongue squamous cell carcinoma Homo sapiens CVCL_1681
Hs 680.Tg Normal Homo sapiens CVCL_0842
FaDu Hypopharyngeal squamous cell carcinoma Homo sapiens CVCL_1218
CAL-27 Tongue squamous cell carcinoma Homo sapiens CVCL_1107
In-vivo Model Lentiviruses containing sh-METTL-14 and its negative control (RiboBio Co., Ltd., Guangzhou, China) were transduced into CAL27 cells and stably transduced cells were screened using puromycin. CAL27 cells (3 × 106 cells/mouse) were subcutaneously inoculated into the posterior flank of each mouse (N = 12/group).
Lung cancer [ICD-11: 2C25]
 Disease Info 
In total 4 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [13]
Response Summary IGF2BP2 promotes Metastasis associated lung adenocarcinoma transcript 1 (MALAT1) stability in an m6A-dependent mechanism, thus promoting its downstream target autophagy-related (ATG)12 expression and NSCLC proliferation.
Responsed Disease Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulator Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) READER
 Regulator Info 
Target Regulation Up regulation
Pathway Response Lysosome hsa04142
Cell Process Cell autophagy
In-vitro Model NCI-H157 Lung squamous cell carcinoma Homo sapiens CVCL_0463
NCI-H460 Lung large cell carcinoma Homo sapiens CVCL_0459
NCI-H1975 Lung adenocarcinoma Homo sapiens CVCL_1511
NCI-H1703 Lung squamous cell carcinoma Homo sapiens CVCL_1490
NCI-H1299 Lung large cell carcinoma Homo sapiens CVCL_0060
BEAS-2B Normal Homo sapiens CVCL_0168
A-549 Lung adenocarcinoma Homo sapiens CVCL_0023
In-vivo Model Mice (male and 6 weeks old) were subcutaneously injected with NSCLC cells (1.0*106 cells/200 uL). The mice were terminated after 4 weeks of induction, and the tumor volume and tumor weight were measured.
Experiment 2 Reporting the m6A-centered Disease Response [2]
Response Summary METTL3, YTHDF3, YTHDF1, and eIF3b directly promoted YAP translation through an interaction with the translation initiation machinery. METTL3 knockdown inhibits tumor growth and enhances sensitivity to DDP in vivo.m6A mRNA methylation initiated by METTL3 directly promotes YAP translation and increases YAP activity by regulating the Metastasis associated lung adenocarcinoma transcript 1 (MALAT1)-miR-1914-3p-YAP axis to induce Non-small cell lung cancer drug resistance and metastasis.
Responsed Disease Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Up regulation
Responsed Drug Cisplatin Approved
 Drug Info 
Pathway Response Hippo signaling pathway hsa04390
Cell Process Metabolic
In-vitro Model A-549 Lung adenocarcinoma Homo sapiens CVCL_0023
Calu-6 Lung adenocarcinoma Homo sapiens CVCL_0236
NCI-H1299 Lung large cell carcinoma Homo sapiens CVCL_0060
NCI-H520 Lung squamous cell carcinoma Homo sapiens CVCL_1566
In-vivo Model Mice were injected with 5 × 106 lung cancer cells with stably expression of relevant plasmids and randomly divided into two groups (five mice per group) after the diameter of the xenografted tumors had reached approximately 5 mm in diameter. Xenografted mice were then administrated with PBS or DDP (3 mg/kg per day) for three times a week, and tumor volume were measured every second day.
Experiment 3 Reporting the m6A-centered Disease Response [2]
Response Summary METTL3, YTHDF3, YTHDF1, and eIF3b directly promoted YAP translation through an interaction with the translation initiation machinery. METTL3 knockdown inhibits tumor growth and enhances sensitivity to DDP in vivo.m6A mRNA methylation initiated by METTL3 directly promotes YAP translation and increases YAP activity by regulating the Metastasis associated lung adenocarcinoma transcript 1 (MALAT1)-miR-1914-3p-YAP axis to induce Non-small cell lung cancer drug resistance and metastasis.
Responsed Disease Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulator YTH domain-containing family protein 1 (YTHDF1) READER
 Regulator Info 
Target Regulation Up regulation
Responsed Drug Cisplatin Approved
 Drug Info 
Pathway Response Hippo signaling pathway hsa04390
Cell Process Metabolic
In-vitro Model A-549 Lung adenocarcinoma Homo sapiens CVCL_0023
Calu-6 Lung adenocarcinoma Homo sapiens CVCL_0236
NCI-H1299 Lung large cell carcinoma Homo sapiens CVCL_0060
NCI-H520 Lung squamous cell carcinoma Homo sapiens CVCL_1566
In-vivo Model Mice were injected with 5 × 106 lung cancer cells with stably expression of relevant plasmids and randomly divided into two groups (five mice per group) after the diameter of the xenografted tumors had reached approximately 5 mm in diameter. Xenografted mice were then administrated with PBS or DDP (3 mg/kg per day) for three times a week, and tumor volume were measured every second day.
Experiment 4 Reporting the m6A-centered Disease Response [2]
Response Summary METTL3, YTHDF3, YTHDF1, and eIF3b directly promoted YAP translation through an interaction with the translation initiation machinery. METTL3 knockdown inhibits tumor growth and enhances sensitivity to DDP in vivo.m6A mRNA methylation initiated by METTL3 directly promotes YAP translation and increases YAP activity by regulating the Metastasis associated lung adenocarcinoma transcript 1 (MALAT1)-miR-1914-3p-YAP axis to induce Non-small cell lung cancer drug resistance and metastasis.
Responsed Disease Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulator YTH domain-containing family protein 3 (YTHDF3) READER
 Regulator Info 
Target Regulation Up regulation
Responsed Drug Cisplatin Approved
 Drug Info 
Pathway Response Hippo signaling pathway hsa04390
Cell Process Metabolic
In-vitro Model A-549 Lung adenocarcinoma Homo sapiens CVCL_0023
Calu-6 Lung adenocarcinoma Homo sapiens CVCL_0236
NCI-H1299 Lung large cell carcinoma Homo sapiens CVCL_0060
NCI-H520 Lung squamous cell carcinoma Homo sapiens CVCL_1566
In-vivo Model Mice were injected with 5 × 106 lung cancer cells with stably expression of relevant plasmids and randomly divided into two groups (five mice per group) after the diameter of the xenografted tumors had reached approximately 5 mm in diameter. Xenografted mice were then administrated with PBS or DDP (3 mg/kg per day) for three times a week, and tumor volume were measured every second day.
Thymoma [ICD-11: 2C27]
 Disease Info 
In total 2 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [3]
Response Summary This study highlighted METTL3 as a tumor promoter in Thymic tumors and c-MYC as a promising target to be exploited for the treatment of TET. High expression of c-MYC protein is enabled by lncRNA Metastasis associated lung adenocarcinoma transcript 1 (MALAT1), which is methylated and delocalized by METTL3. Silencing of METTL3 combined with cisplatin or c-MYC inhibitor induces cell death in TET cells. Blocking of c-MYC by using JQ1 inhibitor cooperates with METTL3 depletion in the inhibition of proliferation and induction of cell death.
Responsed Disease Thymic epithelial tumors [ICD-11: 2C27.Y]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Up regulation
Responsed Drug Cisplatin Approved
 Drug Info 
Pathway Response Cellular senescence hsa04218
Cell Process Cell viability and proliferation
In-vitro Model T1889 Thymic undifferentiated carcinoma Homo sapiens CVCL_D024
Experiment 2 Reporting the m6A-centered Disease Response [3]
Response Summary This study highlighted METTL3 as a tumor promoter in Thymic tumors and c-MYC as a promising target to be exploited for the treatment of TET. High expression of c-MYC protein is enabled by lncRNA Metastasis associated lung adenocarcinoma transcript 1 (MALAT1), which is methylated and delocalized by METTL3. Silencing of METTL3 combined with cisplatin or c-MYC inhibitor induces cell death in TET cells. Blocking of c-MYC by using JQ1 inhibitor cooperates with METTL3 depletion in the inhibition of proliferation and induction of cell death.
Responsed Disease Thymic epithelial tumors [ICD-11: 2C27.Y]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Up regulation
Responsed Drug JQ-1 Phase 1
 Drug Info 
Pathway Response Cellular senescence hsa04218
Cell Process Cell viability and proliferation
In-vitro Model T1889 Thymic undifferentiated carcinoma Homo sapiens CVCL_D024
Breast cancer [ICD-11: 2C60]
 Disease Info 
In total 3 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [4]
Response Summary METTL3 can regulate the expression of Metastasis associated lung adenocarcinoma transcript 1 (MALAT1) through m6A, mediate the E2F1/AGR2 axis, and promote the adriamycin resistance of breast cancer.
Responsed Disease Breast cancer [ICD-11: 2C60]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Up regulation
Responsed Drug Doxil Approved
 Drug Info 
In-vitro Model MCF7-DoxR (Adriamycin-resistant cell line MCF7-DoxR)
MCF-7 Invasive breast carcinoma Homo sapiens CVCL_0031
In-vivo Model Once the tumor volume increased to about 1 cm3, six groups of MCF7 bearing mice (n = 10 in each group) were injected with PBS (0.1 ml, caudal vein) and adriamycin (0.1 ml, 10 mg/kg), respectively. When the tumor reached 1.5 cm in any direction (defined as event-free survival analysis), 10 mice in each group were selected to measure the tumor size and weight on the 12th day after adriamycin injection.
Experiment 2 Reporting the m6A-centered Disease Response [5]
Response Summary Silencing METTL3 down-regulate Metastasis associated lung adenocarcinoma transcript 1 (MALAT1) and HMGA2 by sponging miR-26b, and finally inhibit EMT, migration and invasion in breast cancer, providing a theoretical basis for clinical treatment of breast cancer.
Responsed Disease Breast cancer [ICD-11: 2C60]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Up regulation
Cell Process Epithelial-mesenchymal transition
In-vitro Model MCF-7 Invasive breast carcinoma Homo sapiens CVCL_0031
MDA-MB-231 Breast adenocarcinoma Homo sapiens CVCL_0062
MDA-MB-468 Breast adenocarcinoma Homo sapiens CVCL_0419
MCF-10A Normal Homo sapiens CVCL_0598
Experiment 3 Reporting the m6A-centered Disease Response [5]
Response Summary Silencing METTL3 down-regulate Metastasis associated lung adenocarcinoma transcript 1 (MALAT1) and HMGA2 by sponging miR-26b, and finally inhibit EMT, migration and invasion in BC, providing a theoretical basis for clinical treatment of BC.
Responsed Disease Breast cancer [ICD-11: 2C60]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Up regulation
Cell Process Epithelial-mesenchymal transition
In-vitro Model MDA-MB-468 Breast adenocarcinoma Homo sapiens CVCL_0419
MDA-MB-231 Breast adenocarcinoma Homo sapiens CVCL_0062
MCF-7 Invasive breast carcinoma Homo sapiens CVCL_0031
MCF-10A Normal Homo sapiens CVCL_0598
In-vivo Model Eighteen BALB/C female nude mice aged 4-5 weeks and weighing 15-18 g were randomly assigned into three groups of six mice. The MCF-7 cell lines stably transfected with sh-NC + oe-NC, sh-METTL3 + oe-NC and sh-METTL3 + oe-HMGA2 were selected for subcutaneous establishment of the BC cell line MCF-7 as xenografts in the nude mice. For this purpose, MCF-7 cell lines in the logarithmic growth stage were prepared into a suspension with a concentration of about 1 × 107 cells/ml. The prepared cell suspension was injected into the left armpit of the mice, and the subsequent tumor growth was recorded.
Bladder cancer [ICD-11: 2C94]
 Disease Info 
In total 2 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [8]
Response Summary In bladder cancer, the changes in m6A methylation level mainly appeared at 5' untranslated region (5' UTR) of Metastasis associated lung adenocarcinoma transcript 1 (MALAT1) and NOTCH1 transcripts, and at 3' UTR of CSNK2A2 and ITGA6 transcripts, responding to the overexpression of FTO. SFPQ could influence the FTO-mediated m6A RNA demethylation, eventually affecting the gene expression.
Responsed Disease Bladder cancer [ICD-11: 2C94]
Target Regulator Fat mass and obesity-associated protein (FTO) ERASER
 Regulator Info 
Target Regulation Down regulation
Pathway Response Notch signaling pathway hsa04330
Cell Process Cell proliferation
Cell invasion
Cell apoptosis
In-vitro Model HT-1197 Recurrent bladder carcinoma Homo sapiens CVCL_1291
HT-1376 Bladder carcinoma Homo sapiens CVCL_1292
In-vivo Model BALB/cnu/nu mice (4-5 weeks old) were used for the xenograft experiment. The mice were randomly divided into 2 groups (n = 6 for each group) and injected with 5 × 106 HT-1197 cells in control group or FTO plasmid group, respectively.
Experiment 2 Reporting the m6A-centered Disease Response [9]
Response Summary FTO facilitates the tumorigenesis of bladder cancer through regulating the Metastasis associated lung adenocarcinoma transcript 1 (MALAT1)/miR-384/MAL2 axis in m6A RNA modification manner, which ensures the potential of FTO for serving as a diagnostic or prognostic biomarker in bladder cancer.
Responsed Disease Bladder cancer [ICD-11: 2C94]
Target Regulator Fat mass and obesity-associated protein (FTO) ERASER
 Regulator Info 
Target Regulation Up regulation
Cell Process RNA stability
In-vitro Model T24 Bladder carcinoma Homo sapiens CVCL_0554
SV-HUC-1 Normal Homo sapiens CVCL_3798
SCaBER Bladder squamous cell carcinoma Homo sapiens CVCL_3599
J82 Bladder carcinoma Homo sapiens CVCL_0359
253J Bladder carcinoma Homo sapiens CVCL_7935
5637 Bladder carcinoma Homo sapiens CVCL_0126
In-vivo Model Approximately 5 × 106 253J and 5637 cells infected with indicated vectors were injected subcutaneously into the flank of the mice.
Atopic eczema [ICD-11: EA80]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [14]
Response Summary circRNA hsa_circ_0004287 was upregulated in peripheral blood mononuclear cells of both AD and psoriasis patients. hsa_circ_0004287 reduced the stability of its host gene Metastasis associated lung adenocarcinoma transcript 1 (MALAT1) by competitively binding to IGF2BP3 with MALAT1 in an N6-methyladenosine (m6A)-dependent manner.
Responsed Disease Atopic eczema [ICD-11: EA80]
Target Regulator Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) READER
 Regulator Info 
Target Regulation Up regulation
Pathway Response MAPK signaling pathway hsa04010
Ubiquitin mediated proteolysis hsa04120
Cell Process Inflammation
Proteasome pathway degradation
In-vitro Model RAW 264.7 Mouse leukemia Mus musculus CVCL_0493
In-vivo Model IMQ-induced psoriatic model was constructed by applying 10 mg per ear 5% IMQ for 8 consecutive days, and 6 ug macrophage-specific control or hsa_circ_0004287 plasmid was topically applied every 2 days (5 mice per group per experiment).
Chronic kidney disease [ICD-11: GB61]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [6]
Response Summary Renal fibrosis is a key factor in chronic kidney disease (CKD). Metastasis associated lung adenocarcinoma transcript 1 (MALAT1)/miR-145/FAK pathway was involved in the effect of dihydroartemisinin (DHA) on TGF-beta1-induced renal fibrosis in vitro and in vivo.
Responsed Disease Chronic kidney disease [ICD-11: GB61]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Responsed Drug Artenimol Approved
 Drug Info 
Cell Process Epithelial-mesenchymal transition
In-vitro Model HK-2 [Human kidney] Normal Homo sapiens CVCL_0302
HK2 Normal Acipenser baerii CVCL_YE28
In-vivo Model For the unilateral ureteral obstruction (UUO) model, male C57BL/6J mice at 8 weeks of age (20-22 g body weight) were first anaesthetized with pentobarbital sodium (50 mg/kg) via intraperitoneal injection. Then, the left ureter was ligated using 3-0 silk and a left lateral incision.
Kidney failure [ICD-11: GB6Z]
 Disease Info 
In total 2 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [7]
Response Summary m6A modification is co-regulated by METTL3 and FTO in cadmium-treated cells. Metastasis associated lung adenocarcinoma transcript 1 (MALAT1), LncRNA-PVT1 and m6A modification could be key nodes for cadmium-induced oxidative damage, and highlight their importance as promising preventive and therapeutic targets in cadmium toxicity.
Responsed Disease Kidney failure [ICD-11: GB6Z]
Target Regulator Fat mass and obesity-associated protein (FTO) ERASER
 Regulator Info 
Target Regulation Up regulation
In-vitro Model NIT-1 Insulin tumor Mus musculus CVCL_3561
Experiment 2 Reporting the m6A-centered Disease Response [7]
Response Summary m6A modification is co-regulated by METTL3 and FTO in cadmium-treated cells. Metastasis associated lung adenocarcinoma transcript 1 (MALAT1), LncRNA-PVT1 and m6A modification could be key nodes for cadmium-induced oxidative damage, and highlight their importance as promising preventive and therapeutic targets in cadmium toxicity.
Responsed Disease Kidney failure [ICD-11: GB6Z]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Up regulation
In-vitro Model NIT-1 Insulin tumor Mus musculus CVCL_3561
Urinary/pelvic organs injury [ICD-11: NB92]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [11]
Response Summary ALKBH5 could up-regulate Metastasis associated lung adenocarcinoma transcript 1 (MALAT1) expression by demethylation. Furthermore, dexmedetomidine inhibited the expression of ALKBH5 in LPS-treated HK-2 cells. Dexmedetomidine suppressed the biological behavior of HK-2 cells treated with LPS by inhibiting the expression of ALKBH5 in vitro, which provides potential targets for the prevention and treatment of sepsis-induced kidney injury. Dexmedetomidine suppressed the biological behavior of HK-2 cells treated with LPS by inhibiting the expression of ALKBH5 in vitro, which provides potential targets for the prevention and treatment of sepsis-induced kidney injury.
Responsed Disease Injury of kidney [ICD-11: NB92.0Z]
Target Regulator RNA demethylase ALKBH5 (ALKBH5) ERASER
 Regulator Info 
Target Regulation Up regulation
Cell Process Cell cycle
Cell proliferation
Cell apoptosis
In-vitro Model HK2 Normal Acipenser baerii CVCL_YE28
Artenimol [Approved]
 Drug Info 
In total 1 item(s) under this drug
Experiment 1 Reporting the m6A-centered Drug Response [6]
Response Summary Renal fibrosis is a key factor in chronic kidney disease (CKD). Metastasis associated lung adenocarcinoma transcript 1 (MALAT1)/miR-145/FAK pathway was involved in the effect of dihydroartemisinin (DHA) on TGF-beta1-induced renal fibrosis in vitro and in vivo.
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Responsed Disease Chronic kidney disease ICD-11: GB61
 Disease Info 
Cell Process Epithelial-mesenchymal transition
In-vitro Model HK-2 [Human kidney] Normal Homo sapiens CVCL_0302
HK2 Normal Acipenser baerii CVCL_YE28
In-vivo Model For the unilateral ureteral obstruction (UUO) model, male C57BL/6J mice at 8 weeks of age (20-22 g body weight) were first anaesthetized with pentobarbital sodium (50 mg/kg) via intraperitoneal injection. Then, the left ureter was ligated using 3-0 silk and a left lateral incision.
Cisplatin [Approved]
 Drug Info 
In total 4 item(s) under this drug
Experiment 1 Reporting the m6A-centered Drug Response [2]
Response Summary METTL3, YTHDF3, YTHDF1, and eIF3b directly promoted YAP translation through an interaction with the translation initiation machinery. METTL3 knockdown inhibits tumor growth and enhances sensitivity to DDP in vivo.m6A mRNA methylation initiated by METTL3 directly promotes YAP translation and increases YAP activity by regulating the Metastasis associated lung adenocarcinoma transcript 1 (MALAT1)-miR-1914-3p-YAP axis to induce Non-small cell lung cancer drug resistance and metastasis.
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Up regulation
Responsed Disease Non-small-cell lung carcinoma ICD-11: 2C25.Y
 Disease Info 
Pathway Response Hippo signaling pathway hsa04390
Cell Process Metabolic
In-vitro Model A-549 Lung adenocarcinoma Homo sapiens CVCL_0023
Calu-6 Lung adenocarcinoma Homo sapiens CVCL_0236
NCI-H1299 Lung large cell carcinoma Homo sapiens CVCL_0060
NCI-H520 Lung squamous cell carcinoma Homo sapiens CVCL_1566
In-vivo Model Mice were injected with 5 × 106 lung cancer cells with stably expression of relevant plasmids and randomly divided into two groups (five mice per group) after the diameter of the xenografted tumors had reached approximately 5 mm in diameter. Xenografted mice were then administrated with PBS or DDP (3 mg/kg per day) for three times a week, and tumor volume were measured every second day.
Experiment 2 Reporting the m6A-centered Drug Response [3]
Response Summary This study highlighted METTL3 as a tumor promoter in Thymic tumors and c-MYC as a promising target to be exploited for the treatment of TET. High expression of c-MYC protein is enabled by lncRNA Metastasis associated lung adenocarcinoma transcript 1 (MALAT1), which is methylated and delocalized by METTL3. Silencing of METTL3 combined with cisplatin or c-MYC inhibitor induces cell death in TET cells. Blocking of c-MYC by using JQ1 inhibitor cooperates with METTL3 depletion in the inhibition of proliferation and induction of cell death.
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Up regulation
Responsed Disease Thymic epithelial tumors ICD-11: 2C27.Y
 Disease Info 
Pathway Response Cellular senescence hsa04218
Cell Process Cell viability and proliferation
In-vitro Model T1889 Thymic undifferentiated carcinoma Homo sapiens CVCL_D024
Experiment 3 Reporting the m6A-centered Drug Response [2]
Response Summary METTL3, YTHDF3, YTHDF1, and eIF3b directly promoted YAP translation through an interaction with the translation initiation machinery. METTL3 knockdown inhibits tumor growth and enhances sensitivity to DDP in vivo.m6A mRNA methylation initiated by METTL3 directly promotes YAP translation and increases YAP activity by regulating the Metastasis associated lung adenocarcinoma transcript 1 (MALAT1)-miR-1914-3p-YAP axis to induce Non-small cell lung cancer drug resistance and metastasis.
Target Regulator YTH domain-containing family protein 1 (YTHDF1) READER
 Regulator Info 
Target Regulation Up regulation
Responsed Disease Non-small-cell lung carcinoma ICD-11: 2C25.Y
 Disease Info 
Pathway Response Hippo signaling pathway hsa04390
Cell Process Metabolic
In-vitro Model A-549 Lung adenocarcinoma Homo sapiens CVCL_0023
Calu-6 Lung adenocarcinoma Homo sapiens CVCL_0236
NCI-H1299 Lung large cell carcinoma Homo sapiens CVCL_0060
NCI-H520 Lung squamous cell carcinoma Homo sapiens CVCL_1566
In-vivo Model Mice were injected with 5 × 106 lung cancer cells with stably expression of relevant plasmids and randomly divided into two groups (five mice per group) after the diameter of the xenografted tumors had reached approximately 5 mm in diameter. Xenografted mice were then administrated with PBS or DDP (3 mg/kg per day) for three times a week, and tumor volume were measured every second day.
Experiment 4 Reporting the m6A-centered Drug Response [2]
Response Summary METTL3, YTHDF3, YTHDF1, and eIF3b directly promoted YAP translation through an interaction with the translation initiation machinery. METTL3 knockdown inhibits tumor growth and enhances sensitivity to DDP in vivo.m6A mRNA methylation initiated by METTL3 directly promotes YAP translation and increases YAP activity by regulating the Metastasis associated lung adenocarcinoma transcript 1 (MALAT1)-miR-1914-3p-YAP axis to induce Non-small cell lung cancer drug resistance and metastasis.
Target Regulator YTH domain-containing family protein 3 (YTHDF3) READER
 Regulator Info 
Target Regulation Up regulation
Responsed Disease Non-small-cell lung carcinoma ICD-11: 2C25.Y
 Disease Info 
Pathway Response Hippo signaling pathway hsa04390
Cell Process Metabolic
In-vitro Model A-549 Lung adenocarcinoma Homo sapiens CVCL_0023
Calu-6 Lung adenocarcinoma Homo sapiens CVCL_0236
NCI-H1299 Lung large cell carcinoma Homo sapiens CVCL_0060
NCI-H520 Lung squamous cell carcinoma Homo sapiens CVCL_1566
In-vivo Model Mice were injected with 5 × 106 lung cancer cells with stably expression of relevant plasmids and randomly divided into two groups (five mice per group) after the diameter of the xenografted tumors had reached approximately 5 mm in diameter. Xenografted mice were then administrated with PBS or DDP (3 mg/kg per day) for three times a week, and tumor volume were measured every second day.
Doxil [Approved]
 Drug Info 
In total 1 item(s) under this drug
Experiment 1 Reporting the m6A-centered Drug Response [4]
Response Summary METTL3 can regulate the expression of Metastasis associated lung adenocarcinoma transcript 1 (MALAT1) through m6A, mediate the E2F1/AGR2 axis, and promote the adriamycin resistance of breast cancer.
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Up regulation
Responsed Disease Breast cancer ICD-11: 2C60
 Disease Info 
In-vitro Model MCF7-DoxR (Adriamycin-resistant cell line MCF7-DoxR)
MCF-7 Invasive breast carcinoma Homo sapiens CVCL_0031
In-vivo Model Once the tumor volume increased to about 1 cm3, six groups of MCF7 bearing mice (n = 10 in each group) were injected with PBS (0.1 ml, caudal vein) and adriamycin (0.1 ml, 10 mg/kg), respectively. When the tumor reached 1.5 cm in any direction (defined as event-free survival analysis), 10 mice in each group were selected to measure the tumor size and weight on the 12th day after adriamycin injection.
JQ-1 [Phase 1]
 Drug Info 
In total 1 item(s) under this drug
Experiment 1 Reporting the m6A-centered Drug Response [3]
Response Summary This study highlighted METTL3 as a tumor promoter in Thymic tumors and c-MYC as a promising target to be exploited for the treatment of TET. High expression of c-MYC protein is enabled by lncRNA Metastasis associated lung adenocarcinoma transcript 1 (MALAT1), which is methylated and delocalized by METTL3. Silencing of METTL3 combined with cisplatin or c-MYC inhibitor induces cell death in TET cells. Blocking of c-MYC by using JQ1 inhibitor cooperates with METTL3 depletion in the inhibition of proliferation and induction of cell death.
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Up regulation
Responsed Disease Thymic epithelial tumors ICD-11: 2C27.Y
 Disease Info 
Pathway Response Cellular senescence hsa04218
Cell Process Cell viability and proliferation
In-vitro Model T1889 Thymic undifferentiated carcinoma Homo sapiens CVCL_D024
References
Ref 1 METTL3 enhances the stability of MALAT1 with the assistance of HuR via m6A modification and activates NF-KappaB to promote the malignant progression of IDH-wildtype glioma. Cancer Lett. 2021 Jul 28;511:36-46. doi: 10.1016/j.canlet.2021.04.020. Epub 2021 Apr 29.
Ref 2 m(6)A mRNA methylation initiated by METTL3 directly promotes YAP translation and increases YAP activity by regulating the MALAT1-miR-1914-3p-YAP axis to induce NSCLC drug resistance and metastasis. J Hematol Oncol. 2019 Dec 9;12(1):135. doi: 10.1186/s13045-019-0830-6.
Ref 3 METTL3-dependent MALAT1 delocalization drives c-Myc induction in thymic epithelial tumors. Clin Epigenetics. 2021 Sep 16;13(1):173. doi: 10.1186/s13148-021-01159-6.
Ref 4 Effect of m6A methyltransferase METTL3 -mediated MALAT1/E2F1/AGR2 axis on adriamycin resistance in breast cancer. J Biochem Mol Toxicol. 2022 Jan;36(1):e22922. doi: 10.1002/jbt.22922. Epub 2021 Dec 28.
Ref 5 The m6A methyltransferase METTL3 controls epithelial-mesenchymal transition, migration and invasion of breast cancer through the MALAT1/miR-26b/HMGA2 axis. Cancer Cell Int. 2021 Aug 21;21(1):441. doi: 10.1186/s12935-021-02113-5.
Ref 6 m(6)A-induced lncRNA MALAT1 aggravates renal fibrogenesis in obstructive nephropathy through the miR-145/FAK pathway. Aging (Albany NY). 2020 Mar 23;12(6):5280-5299. doi: 10.18632/aging.102950. Epub 2020 Mar 23.
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