m6A Target Gene Information

General Information of the m6A Target Gene (ID: M6ATAR00196)
Target Name Apoptosis regulator Bcl-2 (BCL2)
Gene Name BCL2
Chromosomal Location 18q21.33
Family Bcl-2 family
Function
Suppresses apoptosis in a variety of cell systems including factor-dependent lymphohematopoietic and neural cells . Regulates cell death by controlling the mitochondrial membrane permeability. Appears to function in a feedback loop system with caspases. Inhibits caspase activity either by preventing the release of cytochrome c from the mitochondria and/or by binding to the apoptosis-activating factor (APAF-1). Also acts as an inhibitor of autophagy: interacts with BECN1 and AMBRA1 during non-starvation conditions and inhibits their autophagy function. May attenuate inflammation by impairing NLRP1-inflammasome activation, hence CASP1 activation and IL1B release.
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Gene ID 596
Uniprot ID
BCL2_HUMAN
HGNC ID
HGNC:990
Ensembl Gene ID
ENSG00000171791
KEGG ID
hsa:596
Full List of m6A Methylation Regulator of This Target Gene and Corresponding Disease/Drug Response(s)
BCL2 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).
Browse Regulator
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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 Th1 cell line Mus musculus
Treatment: METTL3 knockout splenic Th1 cells
Control: Wild type splenic Th1 cells
 GSE129648
Regulation
logFC: 7.38E-01
p-value: 3.55E-06
More Results Click to View More RNA-seq Results
Representative RIP-seq result supporting the interaction between BCL2 and the regulator
Cell Line MDA-MB-231 Homo sapiens
Regulation logFC: 6.70E+00 GSE60213
In total 6 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [1]
Response Summary Knocking down METTL3 prevented Enterovirus 71-induced cell death and suppressed Enterovirus 71-induced expression of BAX while rescuing Apoptosis regulator Bcl-2 (BCL2) expression after Enterovirus 71 infection. Knocking down METTL3 inhibited Enterovirus 71-induced expression of Atg5, Atg7 and LC3 II. Knocking down METTL3 inhibited Enterovirus 71-induced apoptosis and autophagy.
Target Regulation Down regulation
Responsed Disease Enterovirus ICD-11: 1A2Y
 Disease Info 
Pathway Response Autophagy hsa04140
Apoptosis hsa04210
Cell Process Cell proliferation and metastasis
Cell apoptosis
Cell autophagy
In-vitro Model Schwann cells (A type of glial cell that surrounds neurons)
Experiment 2 Reporting the m6A Methylation Regulator of This Target Gene [2]
Response Summary METTL3 depletion in human myeloid leukemia cell lines induces cell differentiation and apoptosis and delays leukemia progression in recipient mice in vivo. Single-nucleotide-resolution mapping of m6A coupled with ribosome profiling reveals that m6A promotes the translation of c-MYC, Apoptosis regulator Bcl-2 (BCL2) and PTEN mRNAs in the human acute myeloid leukemia MOLM-13 cell line. Moreover, loss of METTL3 leads to increased levels of phosphorylated AKT.
Target Regulation Up regulation
Responsed Disease Acute myeloid leukaemia ICD-11: 2A60
 Disease Info 
Pathway Response Apoptosis hsa04210
Cell Process Cell differentiation and apoptosis
In-vitro Model HSPC (Human hematopoietic stem cell)
In-vivo Model 500,000 selected cells were injected via tail vein or retro-orbital route into female NSG (6-8 week old) recipient mice that had been sublethally irradiated with 475 cGy one day before transplantation.
Experiment 3 Reporting the m6A Methylation Regulator of This Target Gene [3]
Response Summary Mettl3 inhibitor, S-adenosylhomocysteine promoted the apoptosis and autophagy of chondrocytes with inflammation in vitro and aggravated the degeneration of chondrocytes and subchondral bone in monosodium iodoacetate (MIA) induced temporomandibular joint osteoarthritis mice in vivo. Bcl2 protein interacted with Beclin1 protein in chondrocytes induced by TNF-alpha stimulation. Mettl3 inhibits the apoptosis and autophagy of chondrocytes in inflammation through m6A/Ythdf1/Apoptosis regulator Bcl-2 (BCL2) signal axis which provides promising therapeutic strategy for temporomandibular joint osteoarthritis.
Target Regulation Up regulation
Responsed Disease B-cell lymphomas ICD-11: 2A86
 Disease Info 
Pathway Response Apoptosis hsa04210
Autophagy hsa04140
Cell Process Cell proliferation and metastasis
Cell apoptosis
In-vitro Model ATDC-5 Mouse teratocarcinoma Mus musculus CVCL_3894
In-vivo Model For MIA + SAH control, S-adenosylhomocysteine (SAH), Mettl3 inhibitor (10 mg/kg) (MCE, NJ, USA) was injected intraperitoneally before MIA injection and maintained twice a week until mice were sacrificed.
Experiment 4 Reporting the m6A Methylation Regulator of This Target Gene [4]
Response Summary Down-regulation of METTL3 inhibits the proliferation and mobility of human gastric cancer cells and leads to inactivation of the AKT signaling pathway, suggesting that METTL3 is a potential target for the treatment of human gastric cancer. METTL3 knockdown decreased Apoptosis regulator Bcl-2 (BCL2) and increased Bax and active Caspase-3 in gastric cancer cells, which suggested the apoptotic pathway was activated. METTL3 led to inactivation of the AKT signaling pathway in human gastric cancer cells, including decreased phosphorylation levels of AKT and expression of down-stream effectors p70S6K and Cyclin D1.
Target Regulation Up regulation
Responsed Disease Gastric cancer ICD-11: 2B72
 Disease Info 
Pathway Response Apoptosis hsa04210
PI3K-Akt signaling pathway hsa04151
Cell Process Cell proliferation
Cell migration
Cell invasion
In-vitro Model AGS Gastric adenocarcinoma Homo sapiens CVCL_0139
MKN45 Gastric adenocarcinoma Homo sapiens CVCL_0434
Experiment 5 Reporting the m6A Methylation Regulator of This Target Gene [5]
Response Summary METTL3 regulated cellular growth, survival and migration in non-small cell lung cancer. METTL3 promoted non-small cell lung cancer progression by modulating the level of Apoptosis regulator Bcl-2 (BCL2).
Target Regulation Up regulation
Responsed Disease Non-small-cell lung carcinoma ICD-11: 2C25.Y
 Disease Info 
Pathway Response Apoptosis hsa04210
Cell Process Cell apoptosis
In-vitro Model A-549 Lung adenocarcinoma Homo sapiens CVCL_0023
BEAS-2B Normal Homo sapiens CVCL_0168
NCI-H1299 Lung large cell carcinoma Homo sapiens CVCL_0060
NCI-H1975 Lung adenocarcinoma Homo sapiens CVCL_1511
HCC827 Lung adenocarcinoma Homo sapiens CVCL_2063
PC-9 Lung adenocarcinoma Homo sapiens CVCL_B260
In-vivo Model The mice were housed with filtered air, 12 h light/dark cycle, constant temperature (25℃), relative humidity (50±5%) and free access to food and water. In order to establish a human NSCLC xenograft model, 5×106 H1299, sh-METTL3-H1299 and METTL3 stably overexpressed H1299 cells (2×106 per mouse) were subcutaneously injected into mice. Tumor growth was observed daily. Tumor volume was calculated as follows: 0.5× (length × width2). At 24 days post-inoculation, the maximum diameter exhibited by a single subcutaneous tumor was 15 mm and mice were anesthetized by intraperitoneal administration of sodium pentobarbital (50 mg/kg), then sacrificed by cervical dislocation.
Experiment 6 Reporting the m6A Methylation Regulator of This Target Gene [6]
Response Summary Apoptosis regulator Bcl-2 (BCL2) acted as the target of METTL3, thereby regulating the proliferation and apoptosis of breast cancer.
Target Regulation Up regulation
Responsed Disease Breast cancer ICD-11: 2C60
 Disease Info 
Pathway Response Apoptosis hsa04210
Cell Process Cell apoptosis
In-vitro Model MCF-10A Normal Homo sapiens CVCL_0598
MCF-7 Invasive breast carcinoma Homo sapiens CVCL_0031
MDA-MB-231 Breast adenocarcinoma Homo sapiens CVCL_0062
MDA-MB-453 Breast adenocarcinoma Homo sapiens CVCL_0418
MDA-MB-468 Breast adenocarcinoma Homo sapiens CVCL_0419
In-vivo Model Mice were maintained at 22 ± 2 ℃ with a humidity of 35 ± 5% under a 12 h light and 12 h dark cycle, with free access to water and food. For the HFD experiment, female control (Ftoflox/flox) and adipose-selective fto knockout (Fabp4-Cre Ftoflox/flox, fto-AKO) mice were fed with high-fat diet (60% fat in calories; Research Diets, D12492) for the desired periods of time, and food intake and body weight were measured every week after weaning (at 3 weeks of age).
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: -6.55E-01
p-value: 1.57E-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 [7]
Response Summary Studies of the aberrant expression of m6A mediators in breast cancer revealed that they were associated with different BC subtypes and functions, such as proliferation, apoptosis, stemness, the cell cycle, migration, and metastasis, through several factors and signaling pathways, such as Apoptosis regulator Bcl-2 (BCL2) and the PI3K/Akt pathway, among others. Fat mass and obesity-associated protein (FTO) was identified as the first m6A demethylase, and a series of inhibitors that target FTO were reported to have potential for the treatment of BC by inhibiting cell proliferation and promoting apoptosis.
Responsed Disease Breast cancer ICD-11: 2C60
 Disease Info 
Pathway Response Apoptosis hsa04210
PI3K-Akt signaling pathway hsa04151
Cell Process Cell proliferation
Cell apoptosis
Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) [READER]
 Regulator Info 
Representative RNA-seq result indicating the expression of this target gene regulated by IGF2BP1
Cell Line ES-2 cell line Homo sapiens
Treatment: siIGF2BP1 ES-2 cells
Control: siControl ES-2 cells
 GSE109604
Regulation
logFC: -7.97E-01
p-value: 9.99E-03
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 [8]
Response Summary YBX1 selectively functions in regulating survival of myeloid leukemia cells. YBX1 interacts with insulin-like growth factor 2 messenger RNA (mRNA)-binding proteins (IGF2BPs) and stabilizes m6A-tagged RNA. YBX1 deficiency dysregulates the expression of apoptosis-related genes and promotes mRNA decay of MYC and Apoptosis regulator Bcl-2 (BCL2) in an m6A-dependent manner, which contributes to the defective survival that results from deletion of YBX1.
Target Regulation Up regulation
Responsed Disease Myeloid leukaemia ICD-11: 2B33.1
 Disease Info 
Cell Process Cell apoptosis
In-vitro Model Leukemia stem cell line (Leukemia stem cell line)
Kasumi-1 Myeloid leukemia with maturation Homo sapiens CVCL_0589
MOLM-13 Adult acute myeloid leukemia Homo sapiens CVCL_2119
THP-1 Childhood acute monocytic leukemia Homo sapiens CVCL_0006
MV4-11 Childhood acute monocytic leukemia Homo sapiens CVCL_0064
BV-173 Chronic myelogenous leukemia Homo sapiens CVCL_0181
NOMO-1 Adult acute monocytic leukemia Homo sapiens CVCL_1609
K-562 Chronic myelogenous leukemia Homo sapiens CVCL_0004
KG-1a Adult acute myeloid leukemia Homo sapiens CVCL_1824
Methyltransferase-like 14 (METTL14) [WRITER]
 Regulator Info 
Representative RNA-seq result indicating the expression of this target gene regulated by METTL14
Cell Line MDA-MB-231 Homo sapiens
Treatment: siMETTL14 MDA-MB-231 cells
Control: MDA-MB-231 cells
 GSE81164
Regulation
logFC: 6.46E-01
p-value: 1.74E-05
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 [9]
Response Summary Knocking down METTL14 could inhibit the development of atherosclerosis in high-fat diet-treated APOE mice. After transfection with si-METTL14, the Apoptosis regulator Bcl-2 (BCL2) expression level and the viability of ox-LDL-incubated cells increased, whereas the apoptosis rate and the expressions of Bax and cleaved caspase-3 decreased. However, the effect of METTL14 knockdown was reversed by p65 overexpression.
Target Regulation Down regulation
Responsed Disease Atherosclerosis ICD-11: BD40.Z
 Disease Info 
Pathway Response Apoptosis hsa04210
Cell Process Cell apoptosis
In-vitro Model HUVEC-C Normal Homo sapiens CVCL_2959
EA.hy 926 Normal Homo sapiens CVCL_3901
In-vivo Model The mice were randomly divided into control, Ad-sh-NC, and Ad-sh-METTL14 groups (10 mice per group). The mice in the control group were fed a normal diet, while the Ad-sh-NC and Ad-sh-METTL14 groups were fed a high-fat diet (20% fat and 0.25% cholesterol). Furthermore, 300 uL of constructed sh-NC or sh-METTL14 adenovirus was injected every 3 weeks into the caudal veins of mice from the Ad-sh-NC or Ad-sh-METTL14 groups, respectively. The constructed vectors were obtained from HanBio Technology Co., Ltd. (Shanghai, China). All mice were sacrificed after 24 weeks and the aortas were separated for further experiments.
RNA demethylase ALKBH5 (ALKBH5) [ERASER]
 Regulator Info 
Representative RNA-seq result indicating the expression of this target gene regulated by ALKBH5
Cell Line CAG cell line Homo sapiens
Treatment: shALKBH5 CAG cells
Control: shNC CAG cells
 GSE180214
Regulation
logFC: -7.25E-01
p-value: 1.10E-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 [10]
Response Summary ALKBH5 is a tumor-promoting gene in epithelial ovarian cancer, which is involved in the mTOR pathway and Apoptosis regulator Bcl-2 (BCL2)-Beclin1 complex. ALKBH5 activated EGFR-PIK3CA-AKT-mTOR signaling pathway. ALKBH5 inhibited autophagy of epithelial ovarian cancer through miR-7 and BCL-2.
Target Regulation Up regulation
Responsed Disease Ovarian cancer ICD-11: 2C73
 Disease Info 
Pathway Response PI3K-Akt signaling pathway hsa04151
mTOR signaling pathway hsa04150
Autophagy hsa04140
In-vitro Model A2780 Ovarian endometrioid adenocarcinoma Homo sapiens CVCL_0134
CoC1 Ovarian adenocarcinoma Homo sapiens CVCL_6891
OVCAR-3 Ovarian serous adenocarcinoma Homo sapiens CVCL_0465
SK-OV-3 Ovarian serous cystadenocarcinoma Homo sapiens CVCL_0532
In-vivo Model SKOV3 or A2780 cells were infected with the indicated lentiviral vectors and injected (5 × 106 cells/mouse in 200 uL volume) subcutaneously into the left armpit of 6-week-old BALB/c nude mice. After 21 days, the animals were sacrificed to confirm the presence of tumors and weigh the established tumors
YTH domain-containing family protein 1 (YTHDF1) [READER]
 Regulator Info 
Representative RIP-seq result supporting the interaction between BCL2 and the regulator
Cell Line Hela Homo sapiens
Regulation logFC: 2.25E+00 GSE63591
In total 1 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [3]
Response Summary Mettl3 inhibitor, S-adenosylhomocysteine promoted the apoptosis and autophagy of chondrocytes with inflammation in vitro and aggravated the degeneration of chondrocytes and subchondral bone in monosodium iodoacetate (MIA) induced temporomandibular joint osteoarthritis mice in vivo. Bcl2 protein interacted with Beclin1 protein in chondrocytes induced by TNF-alpha stimulation. Mettl3 inhibits the apoptosis and autophagy of chondrocytes in inflammation through m6A/Ythdf1/Apoptosis regulator Bcl-2 (BCL2) signal axis which provides promising therapeutic strategy for temporomandibular joint osteoarthritis.
Target Regulation Up regulation
Responsed Disease B-cell lymphomas ICD-11: 2A86
 Disease Info 
Pathway Response Apoptosis hsa04210
Autophagy hsa04140
Cell Process Cell proliferation and metastasis
Cell apoptosis
In-vitro Model ATDC-5 Mouse teratocarcinoma Mus musculus CVCL_3894
In-vivo Model For MIA + SAH control, S-adenosylhomocysteine (SAH), Mettl3 inhibitor (10 mg/kg) (MCE, NJ, USA) was injected intraperitoneally before MIA injection and maintained twice a week until mice were sacrificed.
Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) [READER]
 Regulator Info 
In total 1 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [8]
Response Summary YBX1 selectively functions in regulating survival of myeloid leukemia cells. YBX1 interacts with insulin-like growth factor 2 messenger RNA (mRNA)-binding proteins (IGF2BPs) and stabilizes m6A-tagged RNA. YBX1 deficiency dysregulates the expression of apoptosis-related genes and promotes mRNA decay of MYC and Apoptosis regulator Bcl-2 (BCL2) in an m6A-dependent manner, which contributes to the defective survival that results from deletion of YBX1.
Target Regulation Up regulation
Responsed Disease Myeloid leukaemia ICD-11: 2B33.1
 Disease Info 
Cell Process Cell apoptosis
In-vitro Model Leukemia stem cell line (Leukemia stem cell line)
Kasumi-1 Myeloid leukemia with maturation Homo sapiens CVCL_0589
MOLM-13 Adult acute myeloid leukemia Homo sapiens CVCL_2119
THP-1 Childhood acute monocytic leukemia Homo sapiens CVCL_0006
MV4-11 Childhood acute monocytic leukemia Homo sapiens CVCL_0064
BV-173 Chronic myelogenous leukemia Homo sapiens CVCL_0181
NOMO-1 Adult acute monocytic leukemia Homo sapiens CVCL_1609
K-562 Chronic myelogenous leukemia Homo sapiens CVCL_0004
KG-1a Adult acute myeloid leukemia Homo sapiens CVCL_1824
Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) [READER]
 Regulator Info 
In total 1 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [8]
Response Summary YBX1 selectively functions in regulating survival of myeloid leukemia cells. YBX1 interacts with insulin-like growth factor 2 messenger RNA (mRNA)-binding proteins (IGF2BPs) and stabilizes m6A-tagged RNA. YBX1 deficiency dysregulates the expression of apoptosis-related genes and promotes mRNA decay of MYC and Apoptosis regulator Bcl-2 (BCL2) in an m6A-dependent manner, which contributes to the defective survival that results from deletion of YBX1.
Target Regulation Up regulation
Responsed Disease Myeloid leukaemia ICD-11: 2B33.1
 Disease Info 
Cell Process Cell apoptosis
In-vitro Model Leukemia stem cell line (Leukemia stem cell line)
Kasumi-1 Myeloid leukemia with maturation Homo sapiens CVCL_0589
MOLM-13 Adult acute myeloid leukemia Homo sapiens CVCL_2119
THP-1 Childhood acute monocytic leukemia Homo sapiens CVCL_0006
MV4-11 Childhood acute monocytic leukemia Homo sapiens CVCL_0064
BV-173 Chronic myelogenous leukemia Homo sapiens CVCL_0181
NOMO-1 Adult acute monocytic leukemia Homo sapiens CVCL_1609
K-562 Chronic myelogenous leukemia Homo sapiens CVCL_0004
KG-1a Adult acute myeloid leukemia Homo sapiens CVCL_1824
Enterovirus [ICD-11: 1A2Y]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [1]
Response Summary Knocking down METTL3 prevented Enterovirus 71-induced cell death and suppressed Enterovirus 71-induced expression of BAX while rescuing Apoptosis regulator Bcl-2 (BCL2) expression after Enterovirus 71 infection. Knocking down METTL3 inhibited Enterovirus 71-induced expression of Atg5, Atg7 and LC3 II. Knocking down METTL3 inhibited Enterovirus 71-induced apoptosis and autophagy.
Responsed Disease Enterovirus [ICD-11: 1A2Y]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Down regulation
Pathway Response Autophagy hsa04140
Apoptosis hsa04210
Cell Process Cell proliferation and metastasis
Cell apoptosis
Cell autophagy
In-vitro Model Schwann cells (A type of glial cell that surrounds neurons)
Acute myeloid leukaemia [ICD-11: 2A60]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [2]
Response Summary METTL3 depletion in human myeloid leukemia cell lines induces cell differentiation and apoptosis and delays leukemia progression in recipient mice in vivo. Single-nucleotide-resolution mapping of m6A coupled with ribosome profiling reveals that m6A promotes the translation of c-MYC, Apoptosis regulator Bcl-2 (BCL2) and PTEN mRNAs in the human acute myeloid leukemia MOLM-13 cell line. Moreover, loss of METTL3 leads to increased levels of phosphorylated AKT.
Responsed Disease Acute myeloid leukaemia [ICD-11: 2A60]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Up regulation
Pathway Response Apoptosis hsa04210
Cell Process Cell differentiation and apoptosis
In-vitro Model HSPC (Human hematopoietic stem cell)
In-vivo Model 500,000 selected cells were injected via tail vein or retro-orbital route into female NSG (6-8 week old) recipient mice that had been sublethally irradiated with 475 cGy one day before transplantation.
B-cell lymphomas [ICD-11: 2A86]
 Disease Info 
In total 2 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [3]
Response Summary Mettl3 inhibitor, S-adenosylhomocysteine promoted the apoptosis and autophagy of chondrocytes with inflammation in vitro and aggravated the degeneration of chondrocytes and subchondral bone in monosodium iodoacetate (MIA) induced temporomandibular joint osteoarthritis mice in vivo. Bcl2 protein interacted with Beclin1 protein in chondrocytes induced by TNF-alpha stimulation. Mettl3 inhibits the apoptosis and autophagy of chondrocytes in inflammation through m6A/Ythdf1/Apoptosis regulator Bcl-2 (BCL2) signal axis which provides promising therapeutic strategy for temporomandibular joint osteoarthritis.
Responsed Disease B-cell lymphomas [ICD-11: 2A86]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Up regulation
Pathway Response Apoptosis hsa04210
Autophagy hsa04140
Cell Process Cell proliferation and metastasis
Cell apoptosis
In-vitro Model ATDC-5 Mouse teratocarcinoma Mus musculus CVCL_3894
In-vivo Model For MIA + SAH control, S-adenosylhomocysteine (SAH), Mettl3 inhibitor (10 mg/kg) (MCE, NJ, USA) was injected intraperitoneally before MIA injection and maintained twice a week until mice were sacrificed.
Experiment 2 Reporting the m6A-centered Disease Response [3]
Response Summary Mettl3 inhibitor, S-adenosylhomocysteine promoted the apoptosis and autophagy of chondrocytes with inflammation in vitro and aggravated the degeneration of chondrocytes and subchondral bone in monosodium iodoacetate (MIA) induced temporomandibular joint osteoarthritis mice in vivo. Bcl2 protein interacted with Beclin1 protein in chondrocytes induced by TNF-alpha stimulation. Mettl3 inhibits the apoptosis and autophagy of chondrocytes in inflammation through m6A/Ythdf1/Apoptosis regulator Bcl-2 (BCL2) signal axis which provides promising therapeutic strategy for temporomandibular joint osteoarthritis.
Responsed Disease B-cell lymphomas [ICD-11: 2A86]
Target Regulator YTH domain-containing family protein 1 (YTHDF1) READER
 Regulator Info 
Target Regulation Up regulation
Pathway Response Apoptosis hsa04210
Autophagy hsa04140
Cell Process Cell proliferation and metastasis
Cell apoptosis
In-vitro Model ATDC-5 Mouse teratocarcinoma Mus musculus CVCL_3894
In-vivo Model For MIA + SAH control, S-adenosylhomocysteine (SAH), Mettl3 inhibitor (10 mg/kg) (MCE, NJ, USA) was injected intraperitoneally before MIA injection and maintained twice a week until mice were sacrificed.
Malignant haematopoietic neoplasm [ICD-11: 2B33]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [8]
Response Summary YBX1 selectively functions in regulating survival of myeloid leukemia cells. YBX1 interacts with insulin-like growth factor 2 messenger RNA (mRNA)-binding proteins (IGF2BPs) and stabilizes m6A-tagged RNA. YBX1 deficiency dysregulates the expression of apoptosis-related genes and promotes mRNA decay of MYC and Apoptosis regulator Bcl-2 (BCL2) in an m6A-dependent manner, which contributes to the defective survival that results from deletion of YBX1.
Responsed Disease Myeloid leukaemia [ICD-11: 2B33.1]
Target Regulator Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) READER
 Regulator Info 
Target Regulation Up regulation
Cell Process Cell apoptosis
In-vitro Model Leukemia stem cell line (Leukemia stem cell line)
Kasumi-1 Myeloid leukemia with maturation Homo sapiens CVCL_0589
MOLM-13 Adult acute myeloid leukemia Homo sapiens CVCL_2119
THP-1 Childhood acute monocytic leukemia Homo sapiens CVCL_0006
MV4-11 Childhood acute monocytic leukemia Homo sapiens CVCL_0064
BV-173 Chronic myelogenous leukemia Homo sapiens CVCL_0181
NOMO-1 Adult acute monocytic leukemia Homo sapiens CVCL_1609
K-562 Chronic myelogenous leukemia Homo sapiens CVCL_0004
KG-1a Adult acute myeloid leukemia Homo sapiens CVCL_1824
Gastric cancer [ICD-11: 2B72]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [4]
Response Summary Down-regulation of METTL3 inhibits the proliferation and mobility of human gastric cancer cells and leads to inactivation of the AKT signaling pathway, suggesting that METTL3 is a potential target for the treatment of human gastric cancer. METTL3 knockdown decreased Apoptosis regulator Bcl-2 (BCL2) and increased Bax and active Caspase-3 in gastric cancer cells, which suggested the apoptotic pathway was activated. METTL3 led to inactivation of the AKT signaling pathway in human gastric cancer cells, including decreased phosphorylation levels of AKT and expression of down-stream effectors p70S6K and Cyclin D1.
Responsed Disease Gastric cancer [ICD-11: 2B72]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Up regulation
Pathway Response Apoptosis hsa04210
PI3K-Akt signaling pathway hsa04151
Cell Process Cell proliferation
Cell migration
Cell invasion
In-vitro Model AGS Gastric adenocarcinoma Homo sapiens CVCL_0139
MKN45 Gastric adenocarcinoma Homo sapiens CVCL_0434
Lung cancer [ICD-11: 2C25]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [5]
Response Summary METTL3 regulated cellular growth, survival and migration in non-small cell lung cancer. METTL3 promoted non-small cell lung cancer progression by modulating the level of Apoptosis regulator Bcl-2 (BCL2).
Responsed Disease Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Up regulation
Pathway Response Apoptosis hsa04210
Cell Process Cell apoptosis
In-vitro Model A-549 Lung adenocarcinoma Homo sapiens CVCL_0023
BEAS-2B Normal Homo sapiens CVCL_0168
NCI-H1299 Lung large cell carcinoma Homo sapiens CVCL_0060
NCI-H1975 Lung adenocarcinoma Homo sapiens CVCL_1511
HCC827 Lung adenocarcinoma Homo sapiens CVCL_2063
PC-9 Lung adenocarcinoma Homo sapiens CVCL_B260
In-vivo Model The mice were housed with filtered air, 12 h light/dark cycle, constant temperature (25℃), relative humidity (50±5%) and free access to food and water. In order to establish a human NSCLC xenograft model, 5×106 H1299, sh-METTL3-H1299 and METTL3 stably overexpressed H1299 cells (2×106 per mouse) were subcutaneously injected into mice. Tumor growth was observed daily. Tumor volume was calculated as follows: 0.5× (length × width2). At 24 days post-inoculation, the maximum diameter exhibited by a single subcutaneous tumor was 15 mm and mice were anesthetized by intraperitoneal administration of sodium pentobarbital (50 mg/kg), then sacrificed by cervical dislocation.
Breast cancer [ICD-11: 2C60]
 Disease Info 
In total 2 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [7]
Response Summary Studies of the aberrant expression of m6A mediators in breast cancer revealed that they were associated with different BC subtypes and functions, such as proliferation, apoptosis, stemness, the cell cycle, migration, and metastasis, through several factors and signaling pathways, such as Apoptosis regulator Bcl-2 (BCL2) and the PI3K/Akt pathway, among others. Fat mass and obesity-associated protein (FTO) was identified as the first m6A demethylase, and a series of inhibitors that target FTO were reported to have potential for the treatment of BC by inhibiting cell proliferation and promoting apoptosis.
Responsed Disease Breast cancer [ICD-11: 2C60]
Target Regulator Fat mass and obesity-associated protein (FTO) ERASER
 Regulator Info 
Pathway Response Apoptosis hsa04210
PI3K-Akt signaling pathway hsa04151
Cell Process Cell proliferation
Cell apoptosis
Experiment 2 Reporting the m6A-centered Disease Response [6]
Response Summary Apoptosis regulator Bcl-2 (BCL2) acted as the target of METTL3, thereby regulating the proliferation and apoptosis of breast cancer.
Responsed Disease Breast cancer [ICD-11: 2C60]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Up regulation
Pathway Response Apoptosis hsa04210
Cell Process Cell apoptosis
In-vitro Model MCF-10A Normal Homo sapiens CVCL_0598
MCF-7 Invasive breast carcinoma Homo sapiens CVCL_0031
MDA-MB-231 Breast adenocarcinoma Homo sapiens CVCL_0062
MDA-MB-453 Breast adenocarcinoma Homo sapiens CVCL_0418
MDA-MB-468 Breast adenocarcinoma Homo sapiens CVCL_0419
In-vivo Model Mice were maintained at 22 ± 2 ℃ with a humidity of 35 ± 5% under a 12 h light and 12 h dark cycle, with free access to water and food. For the HFD experiment, female control (Ftoflox/flox) and adipose-selective fto knockout (Fabp4-Cre Ftoflox/flox, fto-AKO) mice were fed with high-fat diet (60% fat in calories; Research Diets, D12492) for the desired periods of time, and food intake and body weight were measured every week after weaning (at 3 weeks of age).
Ovarian cancer [ICD-11: 2C73]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [10]
Response Summary ALKBH5 is a tumor-promoting gene in epithelial ovarian cancer, which is involved in the mTOR pathway and Apoptosis regulator Bcl-2 (BCL2)-Beclin1 complex. ALKBH5 activated EGFR-PIK3CA-AKT-mTOR signaling pathway. ALKBH5 inhibited autophagy of epithelial ovarian cancer through miR-7 and BCL-2.
Responsed Disease Ovarian cancer [ICD-11: 2C73]
Target Regulator RNA demethylase ALKBH5 (ALKBH5) ERASER
 Regulator Info 
Target Regulation Up regulation
Pathway Response PI3K-Akt signaling pathway hsa04151
mTOR signaling pathway hsa04150
Autophagy hsa04140
In-vitro Model A2780 Ovarian endometrioid adenocarcinoma Homo sapiens CVCL_0134
CoC1 Ovarian adenocarcinoma Homo sapiens CVCL_6891
OVCAR-3 Ovarian serous adenocarcinoma Homo sapiens CVCL_0465
SK-OV-3 Ovarian serous cystadenocarcinoma Homo sapiens CVCL_0532
In-vivo Model SKOV3 or A2780 cells were infected with the indicated lentiviral vectors and injected (5 × 106 cells/mouse in 200 uL volume) subcutaneously into the left armpit of 6-week-old BALB/c nude mice. After 21 days, the animals were sacrificed to confirm the presence of tumors and weigh the established tumors
Atherosclerosis [ICD-11: BD40]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [9]
Response Summary Knocking down METTL14 could inhibit the development of atherosclerosis in high-fat diet-treated APOE mice. After transfection with si-METTL14, the Apoptosis regulator Bcl-2 (BCL2) expression level and the viability of ox-LDL-incubated cells increased, whereas the apoptosis rate and the expressions of Bax and cleaved caspase-3 decreased. However, the effect of METTL14 knockdown was reversed by p65 overexpression.
Responsed Disease Atherosclerosis [ICD-11: BD40.Z]
Target Regulator Methyltransferase-like 14 (METTL14) WRITER
 Regulator Info 
Target Regulation Down regulation
Pathway Response Apoptosis hsa04210
Cell Process Cell apoptosis
In-vitro Model HUVEC-C Normal Homo sapiens CVCL_2959
EA.hy 926 Normal Homo sapiens CVCL_3901
In-vivo Model The mice were randomly divided into control, Ad-sh-NC, and Ad-sh-METTL14 groups (10 mice per group). The mice in the control group were fed a normal diet, while the Ad-sh-NC and Ad-sh-METTL14 groups were fed a high-fat diet (20% fat and 0.25% cholesterol). Furthermore, 300 uL of constructed sh-NC or sh-METTL14 adenovirus was injected every 3 weeks into the caudal veins of mice from the Ad-sh-NC or Ad-sh-METTL14 groups, respectively. The constructed vectors were obtained from HanBio Technology Co., Ltd. (Shanghai, China). All mice were sacrificed after 24 weeks and the aortas were separated for further experiments.
Dentofacial anomalies [ICD-11: DA0E]
 Disease Info 
In total 2 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [3]
Response Summary Mettl3 inhibitor, S-adenosylhomocysteine promoted the apoptosis and autophagy of chondrocytes with inflammation in vitro and aggravated the degeneration of chondrocytes and subchondral bone in monosodium iodoacetate (MIA) induced temporomandibular joint osteoarthritis mice in vivo. Bcl2 protein interacted with Beclin1 protein in chondrocytes induced by TNF-alpha stimulation. Mettl3 inhibits the apoptosis and autophagy of chondrocytes in inflammation through m6A/Ythdf1/Apoptosis regulator Bcl-2 (BCL2) signal axis which provides promising therapeutic strategy for temporomandibular joint osteoarthritis.
Responsed Disease Temporomandibular joint disorders [ICD-11: DA0E.8]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Up regulation
Pathway Response Apoptosis hsa04210
Autophagy hsa04140
Cell Process Cell proliferation and metastasis
Cell apoptosis
In-vitro Model ATDC-5 Mouse teratocarcinoma Mus musculus CVCL_3894
In-vivo Model For MIA + SAH control, S-adenosylhomocysteine (SAH), Mettl3 inhibitor (10 mg/kg) (MCE, NJ, USA) was injected intraperitoneally before MIA injection and maintained twice a week until mice were sacrificed.
Experiment 2 Reporting the m6A-centered Disease Response [3]
Response Summary Mettl3 inhibitor, S-adenosylhomocysteine promoted the apoptosis and autophagy of chondrocytes with inflammation in vitro and aggravated the degeneration of chondrocytes and subchondral bone in monosodium iodoacetate (MIA) induced temporomandibular joint osteoarthritis mice in vivo. Bcl2 protein interacted with Beclin1 protein in chondrocytes induced by TNF-alpha stimulation. Mettl3 inhibits the apoptosis and autophagy of chondrocytes in inflammation through m6A/Ythdf1/Apoptosis regulator Bcl-2 (BCL2) signal axis which provides promising therapeutic strategy for temporomandibular joint osteoarthritis.
Responsed Disease Temporomandibular joint disorders [ICD-11: DA0E.8]
Target Regulator YTH domain-containing family protein 1 (YTHDF1) READER
 Regulator Info 
Target Regulation Up regulation
Pathway Response Apoptosis hsa04210
Autophagy hsa04140
Cell Process Cell proliferation and metastasis
Cell apoptosis
In-vitro Model ATDC-5 Mouse teratocarcinoma Mus musculus CVCL_3894
In-vivo Model For MIA + SAH control, S-adenosylhomocysteine (SAH), Mettl3 inhibitor (10 mg/kg) (MCE, NJ, USA) was injected intraperitoneally before MIA injection and maintained twice a week until mice were sacrificed.
References
Ref 1 Knockdown of METTL3 inhibits enterovirus 71-induced apoptosis of mouse Schwann cell through regulation of autophagy. Pathog Dis. 2021 Jul 28;79(6):ftab036. doi: 10.1093/femspd/ftab036.
Ref 2 The N(6)-methyladenosine (m(6)A)-forming enzyme METTL3 controls myeloid differentiation of normal hematopoietic and leukemia cells. Nat Med. 2017 Nov;23(11):1369-1376. doi: 10.1038/nm.4416. Epub 2017 Sep 18.
Ref 3 Mettl3 inhibits the apoptosis and autophagy of chondrocytes in inflammation through mediating Bcl2 stability via Ythdf1-mediated m(6)A modification. Bone. 2022 Jan;154:116182. doi: 10.1016/j.bone.2021.116182. Epub 2021 Sep 13.
Ref 4 METTL3 Promotes the Proliferation and Mobility of Gastric Cancer Cells. Open Med (Wars). 2019 Mar 2;14:25-31. doi: 10.1515/med-2019-0005. eCollection 2019.
Ref 5 METTL3?mediated m6A modification of Bcl?2 mRNA promotes non?small cell lung cancer progression. Oncol Rep. 2021 Aug;46(2):163. doi: 10.3892/or.2021.8114. Epub 2021 Jun 16.
Ref 6 N6-methyladenosine METTL3 promotes the breast cancer progression via targeting Bcl-2. Gene. 2020 Jan 5;722:144076. doi: 10.1016/j.gene.2019.144076. Epub 2019 Aug 24.
Ref 7 The Complex Roles and Therapeutic Implications of m(6)A Modifications in Breast Cancer. Front Cell Dev Biol. 2021 Jan 11;8:615071. doi: 10.3389/fcell.2020.615071. eCollection 2020.
Ref 8 YBX1 is required for maintaining myeloid leukemia cell survival by regulating BCL2 stability in an m6A-dependent manner. Blood. 2021 Jul 8;138(1):71-85. doi: 10.1182/blood.2020009676.
Ref 9 Methyltransferase-like 14 silencing relieves the development of atherosclerosis via m(6)A modification of p65 mRNA. Bioengineered. 2022 May;13(5):11832-11843. doi: 10.1080/21655979.2022.2031409.
Ref 10 ALKBH5 inhibited autophagy of epithelial ovarian cancer through miR-7 and BCL-2. J Exp Clin Cancer Res. 2019 Apr 15;38(1):163. doi: 10.1186/s13046-019-1159-2.