m6A Target Gene Information

General Information of the m6A Target Gene (ID: M6ATAR00190)
Target Name Ubiquitin-like modifier-activating enzyme ATG7 (ATG7)
Synonyms
ATG12-activating enzyme E1 ATG7; Autophagy-related protein 7; APG7-like; hAGP7; Ubiquitin-activating enzyme E1-like protein; APG7L
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Gene Name ATG7
Chromosomal Location 3p25.3
Family ATG7 family
Function
E1-like activating enzyme involved in the 2 ubiquitin-like systems required for cytoplasm to vacuole transport (Cvt) and autophagy. Activates ATG12 for its conjugation with ATG5 as well as the ATG8 family proteins for their conjugation with phosphatidylethanolamine. Both systems are needed for the ATG8 association to Cvt vesicles and autophagosomes membranes. Required for autophagic death induced by caspase-8 inhibition. Required for mitophagy which contributes to regulate mitochondrial quantity and quality by eliminating the mitochondria to a basal level to fulfill cellular energy requirements and preventing excess ROS production. Modulates p53/TP53 activity to regulate cell cycle and survival during metabolic stress. Plays also a key role in the maintenance of axonal homeostasis, the prevention of axonal degeneration, the maintenance of hematopoietic stem cells, the formation of Paneth cell granules, as well as in adipose differentiation. Plays a role in regulating the liver clock and glucose metabolism by mediating the autophagic degradation of CRY1 (clock repressor) in a time-dependent manner (By similarity).
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Gene ID 10533
Uniprot ID
ATG7_HUMAN
HGNC ID
HGNC:16935
Ensembl Gene ID
ENSG00000197548
KEGG ID
hsa:10533
Full List of m6A Methylation Regulator of This Target Gene and Corresponding Disease/Drug Response(s)
ATG7 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 LX2 cell line Homo sapiens
Treatment: shMETTL3 LX2 cells
Control: shLuc LX2 cells
 GSE207909
Regulation
logFC: 6.17E-01
p-value: 3.67E-05
More Results Click to View More RNA-seq Results
Representative RIP-seq result supporting the interaction between ATG7 and the regulator
Cell Line MDA-MB-231 Homo sapiens
Regulation logFC: 4.77E+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 Bcl-2 expression after Enterovirus 71 infection. Knocking down METTL3 inhibited Enterovirus 71-induced expression of Atg5, Ubiquitin-like modifier-activating enzyme ATG7 (ATG7) and LC3 II. Knocking down METTL3 inhibited Enterovirus 71-induced apoptosis and autophagy.
Target Regulation Up regulation
Responsed Disease Enterovirus ICD-11: 1A2Y
 Disease Info 
Pathway Response Autophagy hsa04140
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 can sensitise hepatocellular carcinoma cells to sorafenib through stabilising forkhead box class O3 (FOXO3) in an m6A-dependent manner and translated by YTHDF1, thereby inhibiting the transcription of autophagy-related genes, including ATG3, ATG5, Ubiquitin-like modifier-activating enzyme ATG7 (ATG7), ATG12, and ATG16L1.
Target Regulation Up regulation
Responsed Disease Hepatocellular carcinoma ICD-11: 2C12.02
 Disease Info 
Responsed Drug Sorafenib Approved
 Drug Info 
Pathway Response FoxO signaling pathway hsa04068
Autophagy hsa04140
Cell Process Cell autophagy
Experiment 3 Reporting the m6A Methylation Regulator of This Target Gene [3]
Response Summary METTL3 could positively regulate the autophagy by targeting the autophagy-related genes such as ATG5, Ubiquitin-like modifier-activating enzyme ATG7 (ATG7), LC3B, and SQSTM1. beta-elemene inhibited the autophagy flux by preventing autophagic lysosome acidification, resulting in increasing expression of SQSTM1 and LC3B-II. beta-elemene could reverse gefitinib resistance in non-small cell lung cancer cells by inhibiting cell autophagy process in a manner of chloroquine. METTL3-mediated autophagy in reversing gefitinib resistance of NSCLC cells by beta-elemene, which shed light on providing potential molecular-therapy target and clinical-treatment method in NSCLC patients with gefitinib resistance.
Target Regulation Up regulation
Responsed Disease Non-small-cell lung carcinoma ICD-11: 2C25.Y
 Disease Info 
Responsed Drug Chloroquine Approved
 Drug Info 
Pathway Response Autophagy hsa04140
Cell Process Autophagic lysosome acidification
In-vitro Model Gefitinib-resistant cell line HCC827GR (Gefitinib-resistant HCC827 cell line)
Gefitinib-resistant cell line PC9GR (Gefitinib-resistant PC9 cell line)
HCC827 Lung adenocarcinoma Homo sapiens CVCL_2063
PC-9 Lung adenocarcinoma Homo sapiens CVCL_B260
In-vivo Model NSCLC gefitinib-resistant cells (5 × 106 cells in 100 uL PBS) were injected subcutaneously into the lateral surface of the left abdomen of 6-week-old female BALB/c nude mice (at least five mice per group to ensure accuracy).
Experiment 4 Reporting the m6A Methylation Regulator of This Target Gene [3]
Response Summary METTL3 could positively regulate the autophagy by targeting the autophagy-related genes such as ATG5, Ubiquitin-like modifier-activating enzyme ATG7 (ATG7), LC3B, and SQSTM1. beta-elemene inhibited the autophagy flux by preventing autophagic lysosome acidification, resulting in increasing expression of SQSTM1 and LC3B-II. beta-elemene could reverse gefitinib resistance in non-small cell lung cancer cells by inhibiting cell autophagy process in a manner of chloroquine. METTL3-mediated autophagy in reversing gefitinib resistance of NSCLC cells by beta-elemene, which shed light on providing potential molecular-therapy target and clinical-treatment method in NSCLC patients with gefitinib resistance.
Target Regulation Up regulation
Responsed Disease Non-small-cell lung carcinoma ICD-11: 2C25.Y
 Disease Info 
Responsed Drug Gefitinib Approved
 Drug Info 
Pathway Response Autophagy hsa04140
Cell Process Autophagic lysosome acidification
In-vitro Model Gefitinib-resistant cell line HCC827GR (Gefitinib-resistant HCC827 cell line)
Gefitinib-resistant cell line PC9GR (Gefitinib-resistant PC9 cell line)
HCC827 Lung adenocarcinoma Homo sapiens CVCL_2063
PC-9 Lung adenocarcinoma Homo sapiens CVCL_B260
In-vivo Model NSCLC gefitinib-resistant cells (5 × 106 cells in 100 uL PBS) were injected subcutaneously into the lateral surface of the left abdomen of 6-week-old female BALB/c nude mice (at least five mice per group to ensure accuracy).
Experiment 5 Reporting the m6A Methylation Regulator of This Target Gene [3]
Response Summary METTL3 could positively regulate the autophagy by targeting the autophagy-related genes such as ATG5, Ubiquitin-like modifier-activating enzyme ATG7 (ATG7), LC3B, and SQSTM1. beta-elemene inhibited the autophagy flux by preventing autophagic lysosome acidification, resulting in increasing expression of SQSTM1 and LC3B-II. beta-elemene could reverse gefitinib resistance in non-small cell lung cancer cells by inhibiting cell autophagy process in a manner of chloroquine. METTL3-mediated autophagy in reversing gefitinib resistance of NSCLC cells by beta-elemene, which shed light on providing potential molecular-therapy target and clinical-treatment method in NSCLC patients with gefitinib resistance.
Target Regulation Up regulation
Responsed Disease Non-small-cell lung carcinoma ICD-11: 2C25.Y
 Disease Info 
Responsed Drug Beta-Elemen Phase 3
 Drug Info 
Pathway Response Autophagy hsa04140
Cell Process Autophagic lysosome acidification
In-vitro Model Gefitinib-resistant cell line HCC827GR (Gefitinib-resistant HCC827 cell line)
Gefitinib-resistant cell line PC9GR (Gefitinib-resistant PC9 cell line)
HCC827 Lung adenocarcinoma Homo sapiens CVCL_2063
PC-9 Lung adenocarcinoma Homo sapiens CVCL_B260
In-vivo Model NSCLC gefitinib-resistant cells (5 × 106 cells in 100 uL PBS) were injected subcutaneously into the lateral surface of the left abdomen of 6-week-old female BALB/c nude mice (at least five mice per group to ensure accuracy).
Experiment 6 Reporting the m6A Methylation Regulator of This Target Gene [4]
Response Summary In osteoarthritis METTL3-mediated m6A modification decreased the expression of autophagy-related 7, an E-1 enzyme crucial for the formation of autophagosomes, by attenuating its RNA stability. Silencing METTL3 enhanced autophagic flux and inhibited Ubiquitin-like modifier-activating enzyme ATG7 (ATG7) expression in OA-FLS.
Target Regulation Down regulation
Responsed Disease Osteoarthritis ICD-11: FA05
 Disease Info 
Pathway Response Autophagy hsa04140
Cell Process Cellular senescence
Cell autophagy
In-vitro Model C-28/I2 Normal Homo sapiens CVCL_0187
FLS (Rat fibroblast synovial cell line)
In-vivo Model Mice were anaesthetized with isoflurane supplied in a mouse anaesthesia apparatus, followed with joint surgery on the right joint by sectioning the medial meniscotibial ligament.
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: 1.18E+00
p-value: 1.81E-03
More Results Click to View More RNA-seq Results
In total 2 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [5]
Response Summary CircRAB11FIP1 promoted autophagy flux of ovarian cancer through DSC1 and miR-129. CircRAB11FIP1 can serve as the possible marker for EOC diagnosis and treatment. CircRAB11FIP1 regulated the mechanism of autophagy through m6A modification and direct binding to mRNA. CircRAB11FIP1 bound to the mRNA of FTO and promoted its expression. CircRAB11FIP1 directly bound to miR-129 and regulated its targets Ubiquitin-like modifier-activating enzyme ATG7 (ATG7) and ATG14. CircRAB11FIP1 bound to desmocollin 1to facilitate its interaction with ATG101. CircRAB11FIP1 mediated mRNA expression levels of ATG5 and ATG7 depending on m6A.
Target Regulation Up regulation
Responsed Disease Malignant mixed epithelial mesenchymal tumour of ovary ICD-11: 2B5D.0
 Disease Info 
Pathway Response Autophagy hsa04140
Cell Process Cell autophagy
In-vitro Model SK-OV-3 Ovarian serous cystadenocarcinoma Homo sapiens CVCL_0532
In-vivo Model The SKOV3 ovarian cancer cell line was transfected with LV2-1 or LV2-NC. Thereafter, BALB/c nude mice (6-week old) were intraperitoneally injected with SKOV3 cells. The mice were killed after 5 weeks, and the number of ascites was determined.
Experiment 2 Reporting the m6A Methylation Regulator of This Target Gene [6]
Response Summary Atg5 and Ubiquitin-like modifier-activating enzyme ATG7 (ATG7) were the targets of YTHDF2 (YTH N6-methyladenosine RNA binding protein 2). Upon FTO silencing, Atg5 and Atg7 transcripts with higher m6A levels were captured by YTHDF2, which resulted in mRNA degradation and reduction of protein expression, thus alleviating autophagy and adipogenesis.
Target Regulation Up regulation
Responsed Disease Obesity ICD-11: 5B81
 Disease Info 
Pathway Response Autophagy hsa04140
Cell Process Autophagy
Adipogenesis regulation
In-vitro Model 3T3-L1 Normal Mus musculus CVCL_0123
Pig primary preadipocytes (Isolated from cervical subcutaneous adipose tissue of piglets)
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).
YTH domain-containing family protein 1 (YTHDF1) [READER]
 Regulator Info 
In total 1 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [2]
Response Summary METTL3 can sensitise hepatocellular carcinoma cells to sorafenib through stabilising forkhead box class O3 (FOXO3) in an m6A-dependent manner and translated by YTHDF1, thereby inhibiting the transcription of autophagy-related genes, including ATG3, ATG5, Ubiquitin-like modifier-activating enzyme ATG7 (ATG7), ATG12, and ATG16L1.
Target Regulation Up regulation
Responsed Disease Hepatocellular carcinoma ICD-11: 2C12.02
 Disease Info 
Responsed Drug Sorafenib Approved
 Drug Info 
Pathway Response FoxO signaling pathway hsa04068
Autophagy hsa04140
Cell Process Cell autophagy
YTH domain-containing family protein 2 (YTHDF2) [READER]
 Regulator Info 
In total 1 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [6]
Response Summary Atg5 and Ubiquitin-like modifier-activating enzyme ATG7 (ATG7) were the targets of YTHDF2 (YTH N6-methyladenosine RNA binding protein 2). Upon FTO silencing, Atg5 and Atg7 transcripts with higher m6A levels were captured by YTHDF2, which resulted in mRNA degradation and reduction of protein expression, thus alleviating autophagy and adipogenesis.
Target Regulation Down regulation
Responsed Disease Obesity ICD-11: 5B81
 Disease Info 
Pathway Response Autophagy hsa04140
Cell Process Autophagy
Adipogenesis regulation
In-vitro Model 3T3-L1 Normal Mus musculus CVCL_0123
Pig primary preadipocytes (Isolated from cervical subcutaneous adipose tissue of piglets)
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).
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 Bcl-2 expression after Enterovirus 71 infection. Knocking down METTL3 inhibited Enterovirus 71-induced expression of Atg5, Ubiquitin-like modifier-activating enzyme ATG7 (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 Up regulation
Pathway Response Autophagy hsa04140
Cell Process Cell proliferation and metastasis
Cell apoptosis
Cell autophagy
In-vitro Model Schwann cells (A type of glial cell that surrounds neurons)
Malignant mixed epithelial mesenchymal tumour [ICD-11: 2B5D]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [5]
Response Summary CircRAB11FIP1 promoted autophagy flux of ovarian cancer through DSC1 and miR-129. CircRAB11FIP1 can serve as the possible marker for EOC diagnosis and treatment. CircRAB11FIP1 regulated the mechanism of autophagy through m6A modification and direct binding to mRNA. CircRAB11FIP1 bound to the mRNA of FTO and promoted its expression. CircRAB11FIP1 directly bound to miR-129 and regulated its targets Ubiquitin-like modifier-activating enzyme ATG7 (ATG7) and ATG14. CircRAB11FIP1 bound to desmocollin 1to facilitate its interaction with ATG101. CircRAB11FIP1 mediated mRNA expression levels of ATG5 and ATG7 depending on m6A.
Responsed Disease Malignant mixed epithelial mesenchymal tumour of ovary [ICD-11: 2B5D.0]
Target Regulator Fat mass and obesity-associated protein (FTO) ERASER
 Regulator Info 
Target Regulation Up regulation
Pathway Response Autophagy hsa04140
Cell Process Cell autophagy
In-vitro Model SK-OV-3 Ovarian serous cystadenocarcinoma Homo sapiens CVCL_0532
In-vivo Model The SKOV3 ovarian cancer cell line was transfected with LV2-1 or LV2-NC. Thereafter, BALB/c nude mice (6-week old) were intraperitoneally injected with SKOV3 cells. The mice were killed after 5 weeks, and the number of ascites was determined.
Liver cancer [ICD-11: 2C12]
 Disease Info 
In total 2 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [2]
Response Summary METTL3 can sensitise hepatocellular carcinoma cells to sorafenib through stabilising forkhead box class O3 (FOXO3) in an m6A-dependent manner and translated by YTHDF1, thereby inhibiting the transcription of autophagy-related genes, including ATG3, ATG5, Ubiquitin-like modifier-activating enzyme ATG7 (ATG7), ATG12, and ATG16L1.
Responsed Disease Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Up regulation
Responsed Drug Sorafenib Approved
 Drug Info 
Pathway Response FoxO signaling pathway hsa04068
Autophagy hsa04140
Cell Process Cell autophagy
Experiment 2 Reporting the m6A-centered Disease Response [2]
Response Summary METTL3 can sensitise hepatocellular carcinoma cells to sorafenib through stabilising forkhead box class O3 (FOXO3) in an m6A-dependent manner and translated by YTHDF1, thereby inhibiting the transcription of autophagy-related genes, including ATG3, ATG5, Ubiquitin-like modifier-activating enzyme ATG7 (ATG7), ATG12, and ATG16L1.
Responsed Disease Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulator YTH domain-containing family protein 1 (YTHDF1) READER
 Regulator Info 
Target Regulation Up regulation
Responsed Drug Sorafenib Approved
 Drug Info 
Pathway Response FoxO signaling pathway hsa04068
Autophagy hsa04140
Cell Process Cell autophagy
Lung cancer [ICD-11: 2C25]
 Disease Info 
In total 3 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [3]
Response Summary METTL3 could positively regulate the autophagy by targeting the autophagy-related genes such as ATG5, Ubiquitin-like modifier-activating enzyme ATG7 (ATG7), LC3B, and SQSTM1. beta-elemene inhibited the autophagy flux by preventing autophagic lysosome acidification, resulting in increasing expression of SQSTM1 and LC3B-II. beta-elemene could reverse gefitinib resistance in non-small cell lung cancer cells by inhibiting cell autophagy process in a manner of chloroquine. METTL3-mediated autophagy in reversing gefitinib resistance of NSCLC cells by beta-elemene, which shed light on providing potential molecular-therapy target and clinical-treatment method in NSCLC patients with gefitinib resistance.
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 Chloroquine Approved
 Drug Info 
Pathway Response Autophagy hsa04140
Cell Process Autophagic lysosome acidification
In-vitro Model Gefitinib-resistant cell line HCC827GR (Gefitinib-resistant HCC827 cell line)
Gefitinib-resistant cell line PC9GR (Gefitinib-resistant PC9 cell line)
HCC827 Lung adenocarcinoma Homo sapiens CVCL_2063
PC-9 Lung adenocarcinoma Homo sapiens CVCL_B260
In-vivo Model NSCLC gefitinib-resistant cells (5 × 106 cells in 100 uL PBS) were injected subcutaneously into the lateral surface of the left abdomen of 6-week-old female BALB/c nude mice (at least five mice per group to ensure accuracy).
Experiment 2 Reporting the m6A-centered Disease Response [3]
Response Summary METTL3 could positively regulate the autophagy by targeting the autophagy-related genes such as ATG5, Ubiquitin-like modifier-activating enzyme ATG7 (ATG7), LC3B, and SQSTM1. beta-elemene inhibited the autophagy flux by preventing autophagic lysosome acidification, resulting in increasing expression of SQSTM1 and LC3B-II. beta-elemene could reverse gefitinib resistance in non-small cell lung cancer cells by inhibiting cell autophagy process in a manner of chloroquine. METTL3-mediated autophagy in reversing gefitinib resistance of NSCLC cells by beta-elemene, which shed light on providing potential molecular-therapy target and clinical-treatment method in NSCLC patients with gefitinib resistance.
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 Gefitinib Approved
 Drug Info 
Pathway Response Autophagy hsa04140
Cell Process Autophagic lysosome acidification
In-vitro Model Gefitinib-resistant cell line HCC827GR (Gefitinib-resistant HCC827 cell line)
Gefitinib-resistant cell line PC9GR (Gefitinib-resistant PC9 cell line)
HCC827 Lung adenocarcinoma Homo sapiens CVCL_2063
PC-9 Lung adenocarcinoma Homo sapiens CVCL_B260
In-vivo Model NSCLC gefitinib-resistant cells (5 × 106 cells in 100 uL PBS) were injected subcutaneously into the lateral surface of the left abdomen of 6-week-old female BALB/c nude mice (at least five mice per group to ensure accuracy).
Experiment 3 Reporting the m6A-centered Disease Response [3]
Response Summary METTL3 could positively regulate the autophagy by targeting the autophagy-related genes such as ATG5, Ubiquitin-like modifier-activating enzyme ATG7 (ATG7), LC3B, and SQSTM1. beta-elemene inhibited the autophagy flux by preventing autophagic lysosome acidification, resulting in increasing expression of SQSTM1 and LC3B-II. beta-elemene could reverse gefitinib resistance in non-small cell lung cancer cells by inhibiting cell autophagy process in a manner of chloroquine. METTL3-mediated autophagy in reversing gefitinib resistance of NSCLC cells by beta-elemene, which shed light on providing potential molecular-therapy target and clinical-treatment method in NSCLC patients with gefitinib resistance.
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 Beta-Elemen Phase 3
 Drug Info 
Pathway Response Autophagy hsa04140
Cell Process Autophagic lysosome acidification
In-vitro Model Gefitinib-resistant cell line HCC827GR (Gefitinib-resistant HCC827 cell line)
Gefitinib-resistant cell line PC9GR (Gefitinib-resistant PC9 cell line)
HCC827 Lung adenocarcinoma Homo sapiens CVCL_2063
PC-9 Lung adenocarcinoma Homo sapiens CVCL_B260
In-vivo Model NSCLC gefitinib-resistant cells (5 × 106 cells in 100 uL PBS) were injected subcutaneously into the lateral surface of the left abdomen of 6-week-old female BALB/c nude mice (at least five mice per group to ensure accuracy).
Obesity [ICD-11: 5B81]
 Disease Info 
In total 2 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [6]
Response Summary Atg5 and Ubiquitin-like modifier-activating enzyme ATG7 (ATG7) were the targets of YTHDF2 (YTH N6-methyladenosine RNA binding protein 2). Upon FTO silencing, Atg5 and Atg7 transcripts with higher m6A levels were captured by YTHDF2, which resulted in mRNA degradation and reduction of protein expression, thus alleviating autophagy and adipogenesis.
Responsed Disease Obesity [ICD-11: 5B81]
Target Regulator Fat mass and obesity-associated protein (FTO) ERASER
 Regulator Info 
Target Regulation Up regulation
Pathway Response Autophagy hsa04140
Cell Process Autophagy
Adipogenesis regulation
In-vitro Model 3T3-L1 Normal Mus musculus CVCL_0123
Pig primary preadipocytes (Isolated from cervical subcutaneous adipose tissue of piglets)
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).
Experiment 2 Reporting the m6A-centered Disease Response [6]
Response Summary Atg5 and Ubiquitin-like modifier-activating enzyme ATG7 (ATG7) were the targets of YTHDF2 (YTH N6-methyladenosine RNA binding protein 2). Upon FTO silencing, Atg5 and Atg7 transcripts with higher m6A levels were captured by YTHDF2, which resulted in mRNA degradation and reduction of protein expression, thus alleviating autophagy and adipogenesis.
Responsed Disease Obesity [ICD-11: 5B81]
Target Regulator YTH domain-containing family protein 2 (YTHDF2) READER
 Regulator Info 
Target Regulation Down regulation
Pathway Response Autophagy hsa04140
Cell Process Autophagy
Adipogenesis regulation
In-vitro Model 3T3-L1 Normal Mus musculus CVCL_0123
Pig primary preadipocytes (Isolated from cervical subcutaneous adipose tissue of piglets)
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).
Osteoarthritis [ICD-11: FA05]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [4]
Response Summary In osteoarthritis METTL3-mediated m6A modification decreased the expression of autophagy-related 7, an E-1 enzyme crucial for the formation of autophagosomes, by attenuating its RNA stability. Silencing METTL3 enhanced autophagic flux and inhibited Ubiquitin-like modifier-activating enzyme ATG7 (ATG7) expression in OA-FLS.
Responsed Disease Osteoarthritis [ICD-11: FA05]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Down regulation
Pathway Response Autophagy hsa04140
Cell Process Cellular senescence
Cell autophagy
In-vitro Model C-28/I2 Normal Homo sapiens CVCL_0187
FLS (Rat fibroblast synovial cell line)
In-vivo Model Mice were anaesthetized with isoflurane supplied in a mouse anaesthesia apparatus, followed with joint surgery on the right joint by sectioning the medial meniscotibial ligament.
Chloroquine [Approved]
 Drug Info 
In total 1 item(s) under this drug
Experiment 1 Reporting the m6A-centered Drug Response [3]
Response Summary METTL3 could positively regulate the autophagy by targeting the autophagy-related genes such as ATG5, Ubiquitin-like modifier-activating enzyme ATG7 (ATG7), LC3B, and SQSTM1. beta-elemene inhibited the autophagy flux by preventing autophagic lysosome acidification, resulting in increasing expression of SQSTM1 and LC3B-II. beta-elemene could reverse gefitinib resistance in non-small cell lung cancer cells by inhibiting cell autophagy process in a manner of chloroquine. METTL3-mediated autophagy in reversing gefitinib resistance of NSCLC cells by beta-elemene, which shed light on providing potential molecular-therapy target and clinical-treatment method in NSCLC patients with gefitinib resistance.
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 Autophagy hsa04140
Cell Process Autophagic lysosome acidification
In-vitro Model Gefitinib-resistant cell line HCC827GR (Gefitinib-resistant HCC827 cell line)
Gefitinib-resistant cell line PC9GR (Gefitinib-resistant PC9 cell line)
HCC827 Lung adenocarcinoma Homo sapiens CVCL_2063
PC-9 Lung adenocarcinoma Homo sapiens CVCL_B260
In-vivo Model NSCLC gefitinib-resistant cells (5 × 106 cells in 100 uL PBS) were injected subcutaneously into the lateral surface of the left abdomen of 6-week-old female BALB/c nude mice (at least five mice per group to ensure accuracy).
Gefitinib [Approved]
 Drug Info 
In total 1 item(s) under this drug
Experiment 1 Reporting the m6A-centered Drug Response [3]
Response Summary METTL3 could positively regulate the autophagy by targeting the autophagy-related genes such as ATG5, Ubiquitin-like modifier-activating enzyme ATG7 (ATG7), LC3B, and SQSTM1. beta-elemene inhibited the autophagy flux by preventing autophagic lysosome acidification, resulting in increasing expression of SQSTM1 and LC3B-II. beta-elemene could reverse gefitinib resistance in non-small cell lung cancer cells by inhibiting cell autophagy process in a manner of chloroquine. METTL3-mediated autophagy in reversing gefitinib resistance of NSCLC cells by beta-elemene, which shed light on providing potential molecular-therapy target and clinical-treatment method in NSCLC patients with gefitinib resistance.
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 Autophagy hsa04140
Cell Process Autophagic lysosome acidification
In-vitro Model Gefitinib-resistant cell line HCC827GR (Gefitinib-resistant HCC827 cell line)
Gefitinib-resistant cell line PC9GR (Gefitinib-resistant PC9 cell line)
HCC827 Lung adenocarcinoma Homo sapiens CVCL_2063
PC-9 Lung adenocarcinoma Homo sapiens CVCL_B260
In-vivo Model NSCLC gefitinib-resistant cells (5 × 106 cells in 100 uL PBS) were injected subcutaneously into the lateral surface of the left abdomen of 6-week-old female BALB/c nude mice (at least five mice per group to ensure accuracy).
Sorafenib [Approved]
 Drug Info 
In total 2 item(s) under this drug
Experiment 1 Reporting the m6A-centered Drug Response [2]
Response Summary METTL3 can sensitise hepatocellular carcinoma cells to sorafenib through stabilising forkhead box class O3 (FOXO3) in an m6A-dependent manner and translated by YTHDF1, thereby inhibiting the transcription of autophagy-related genes, including ATG3, ATG5, Ubiquitin-like modifier-activating enzyme ATG7 (ATG7), ATG12, and ATG16L1.
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Up regulation
Responsed Disease Hepatocellular carcinoma ICD-11: 2C12.02
 Disease Info 
Pathway Response FoxO signaling pathway hsa04068
Autophagy hsa04140
Cell Process Cell autophagy
Experiment 2 Reporting the m6A-centered Drug Response [2]
Response Summary METTL3 can sensitise hepatocellular carcinoma cells to sorafenib through stabilising forkhead box class O3 (FOXO3) in an m6A-dependent manner and translated by YTHDF1, thereby inhibiting the transcription of autophagy-related genes, including ATG3, ATG5, Ubiquitin-like modifier-activating enzyme ATG7 (ATG7), ATG12, and ATG16L1.
Target Regulator YTH domain-containing family protein 1 (YTHDF1) READER
 Regulator Info 
Target Regulation Up regulation
Responsed Disease Hepatocellular carcinoma ICD-11: 2C12.02
 Disease Info 
Pathway Response FoxO signaling pathway hsa04068
Autophagy hsa04140
Cell Process Cell autophagy
Beta-Elemen [Phase 3]
 Drug Info 
In total 1 item(s) under this drug
Experiment 1 Reporting the m6A-centered Drug Response [3]
Response Summary METTL3 could positively regulate the autophagy by targeting the autophagy-related genes such as ATG5, Ubiquitin-like modifier-activating enzyme ATG7 (ATG7), LC3B, and SQSTM1. beta-elemene inhibited the autophagy flux by preventing autophagic lysosome acidification, resulting in increasing expression of SQSTM1 and LC3B-II. beta-elemene could reverse gefitinib resistance in non-small cell lung cancer cells by inhibiting cell autophagy process in a manner of chloroquine. METTL3-mediated autophagy in reversing gefitinib resistance of NSCLC cells by beta-elemene, which shed light on providing potential molecular-therapy target and clinical-treatment method in NSCLC patients with gefitinib resistance.
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 Autophagy hsa04140
Cell Process Autophagic lysosome acidification
In-vitro Model Gefitinib-resistant cell line HCC827GR (Gefitinib-resistant HCC827 cell line)
Gefitinib-resistant cell line PC9GR (Gefitinib-resistant PC9 cell line)
HCC827 Lung adenocarcinoma Homo sapiens CVCL_2063
PC-9 Lung adenocarcinoma Homo sapiens CVCL_B260
In-vivo Model NSCLC gefitinib-resistant cells (5 × 106 cells in 100 uL PBS) were injected subcutaneously into the lateral surface of the left abdomen of 6-week-old female BALB/c nude mice (at least five mice per group to ensure accuracy).
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 RNA N6-methyladenosine: a new player in autophagy-mediated anti-cancer drug resistance. Br J Cancer. 2021 May;124(10):1621-1622. doi: 10.1038/s41416-021-01314-z. Epub 2021 Mar 15.
Ref 3 The mechanism of m(6)A methyltransferase METTL3-mediated autophagy in reversing gefitinib resistance in NSCLC cells by Beta-elemene. Cell Death Dis. 2020 Nov 11;11(11):969. doi: 10.1038/s41419-020-03148-8.
Ref 4 METTL3-mediated m(6)A modification of ATG7 regulates autophagy-GATA4 axis to promote cellular senescence and osteoarthritis progression. Ann Rheum Dis. 2022 Jan;81(1):87-99. doi: 10.1136/annrheumdis-2021-221091. Epub 2021 Oct 27.
Ref 5 CircRAB11FIP1 promoted autophagy flux of ovarian cancer through DSC1 and miR-129. Cell Death Dis. 2021 Feb 26;12(2):219. doi: 10.1038/s41419-021-03486-1.
Ref 6 m(6)A mRNA methylation controls autophagy and adipogenesis by targeting Atg5 and Atg7. Autophagy. 2020 Jul;16(7):1221-1235. doi: 10.1080/15548627.2019.1659617. Epub 2019 Aug 26.