m6A Target Gene Information

General Information of the m6A Target Gene (ID: M6ATAR00189)

Target Name	Autophagy protein 5 (ATG5)
Synonyms	APG5-like; Apoptosis-specific protein; APG5L; ASP Click to Show/Hide
Gene Name	ATG5
Chromosomal Location	6q21
Family	ATG5 family
Function	Involved in autophagic vesicle formation. Conjugation with ATG12, through a ubiquitin-like conjugating system involving ATG7 as an E1-like activating enzyme and ATG10 as an E2-like conjugating enzyme, is essential for its function. The ATG12-ATG5 conjugate acts as an E3-like enzyme which is required for lipidation of ATG8 family proteins and their association to the vesicle membranes. Involved in mitochondrial quality control after oxidative damage, and in subsequent cellular longevity. Plays a critical role in multiple aspects of lymphocyte development and is essential for both B and T lymphocyte survival and proliferation. Required for optimal processing and presentation of antigens for MHC II. Involved in the maintenance of axon morphology and membrane structures, as well as in normal adipocyte differentiation. Promotes primary ciliogenesis through removal of OFD1 from centriolar satellites and degradation of IFT20 via the autophagic pathway. May play an important role in the apoptotic process, possibly within the modified cytoskeleton. Its expression is a relatively late event in the apoptotic process, occurring downstream of caspase activity. Plays a crucial role in IFN-gamma-induced autophagic cell death by interacting with FADD. (Microbial infection) May act as a proviral factor. In association with ATG12, negatively regulates the innate antiviral immune response by impairing the type I IFN production pathway upon vesicular stomatitis virus (VSV) infection. Required for the translation of incoming hepatitis C virus (HCV) RNA and, thereby, for initiation of HCV replication, but not required once infection is established. Click to Show/Hide
Gene ID	9474
Uniprot ID	ATG5_HUMAN
HGNC ID	HGNC:589
Ensembl Gene ID	ENSG00000057663
KEGG ID	hsa:9474

Full List of m6A Methylation Regulator of This Target Gene and Corresponding Disease/Drug Response(s)

ATG5 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	CT26 cell line	Mus musculus
Treatment: METTL3 knockout CT26 cells Control: CT26 cells		GSE142589
Regulation		logFC: -9.09E-01 p-value: 4.91E-03
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between ATG5 and the regulator*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 8.30E+00	GSE60213

In total 7 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 Autophagy protein 5 (ATG5), 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, Autophagy protein 5 (ATG5), 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 Autophagy protein 5 (ATG5), 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 Autophagy protein 5 (ATG5), 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 Autophagy protein 5 (ATG5), 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	m6A methyltransferase METTL3 regulates autophagy and sensitivity to cisplatin by targeting Autophagy protein 5 (ATG5) in seminoma. The use of autophagy inhibitors 3-MA could reverse the protective effect of METTL3 on TCam-2 cells.
Target Regulation	Up regulation
Responsed Disease	Testicular cancer		ICD-11: 2C80	Disease Info
Responsed Drug	Cisplatin		Approved	Drug Info
Pathway Response	Autophagy			hsa04140
Cell Process	Cellular Processes
	Cellular Transport
	Cellular catabolism
	Cell autophagy
In-vitro Model	Tcam-2/DDP (Cisplatin-resistant TCam-2 cell line)
	TCam-2	Testicular seminoma	Homo sapiens	CVCL_T012
Experiment 7 Reporting the m6A Methylation Regulator of This Target Gene				[4]
Response Summary	m6A methyltransferase METTL3 regulates autophagy and sensitivity to cisplatin by targeting Autophagy protein 5 (ATG5) in seminoma. The use of autophagy inhibitors 3-MA could reverse the protective effect of METTL3 on TCam-2 cells.
Target Regulation	Up regulation
Responsed Disease	Testicular cancer		ICD-11: 2C80	Disease Info
Responsed Drug	3-Methyladenine		Investigative	Drug Info
Pathway Response	Autophagy			hsa04140
Cell Process	Cellular Processes
	Cellular Transport
	Cellular catabolism
	Cell autophagy
In-vitro Model	Tcam-2/DDP (Cisplatin-resistant TCam-2 cell line)
	TCam-2	Testicular seminoma	Homo sapiens	CVCL_T012

YTH domain-containing family protein 2 (YTHDF2) [READER]

Regulator Info

*Representative RIP-seq result supporting the interaction between ATG5 and the regulator*
Cell Line	Hela	Homo sapiens
Regulation	logFC: 2.24E+00	GSE49339

In total 1 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene				[5]
Response Summary	Autophagy protein 5 (ATG5) and 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 (Fto^flox/flox) and adipose-selective fto knockout (Fabp4-Cre Fto^flox/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

In total 2 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene				[6]
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 ATG7 and ATG14. CircRAB11FIP1 bound to desmocollin 1to facilitate its interaction with ATG101. CircRAB11FIP1 mediated mRNA expression levels of Autophagy protein 5 (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				[5]
Response Summary	Autophagy protein 5 (ATG5) and 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 (Fto^flox/flox) and adipose-selective fto knockout (Fabp4-Cre Fto^flox/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, Autophagy protein 5 (ATG5), 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

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 Autophagy protein 5 (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	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				[6]
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 ATG7 and ATG14. CircRAB11FIP1 bound to desmocollin 1to facilitate its interaction with ATG101. CircRAB11FIP1 mediated mRNA expression levels of Autophagy protein 5 (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, Autophagy protein 5 (ATG5), 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, Autophagy protein 5 (ATG5), 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 Autophagy protein 5 (ATG5), 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 Autophagy protein 5 (ATG5), 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 Autophagy protein 5 (ATG5), 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).

Testicular cancer [ICD-11: 2C80]

Disease Info

In total 2 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response				[4]
Response Summary	m6A methyltransferase METTL3 regulates autophagy and sensitivity to cisplatin by targeting Autophagy protein 5 (ATG5) in seminoma. The use of autophagy inhibitors 3-MA could reverse the protective effect of METTL3 on TCam-2 cells.
Responsed Disease	Testicular cancer [ICD-11: 2C80]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Responsed Drug	Cisplatin		Approved	Drug Info
Pathway Response	Autophagy			hsa04140
Cell Process	Cellular Processes
	Cellular Transport
	Cellular catabolism
	Cell autophagy
In-vitro Model	Tcam-2/DDP (Cisplatin-resistant TCam-2 cell line)
	TCam-2	Testicular seminoma	Homo sapiens	CVCL_T012
Experiment 2 Reporting the m6A-centered Disease Response				[4]
Response Summary	m6A methyltransferase METTL3 regulates autophagy and sensitivity to cisplatin by targeting Autophagy protein 5 (ATG5) in seminoma. The use of autophagy inhibitors 3-MA could reverse the protective effect of METTL3 on TCam-2 cells.
Responsed Disease	Testicular cancer [ICD-11: 2C80]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Responsed Drug	3-Methyladenine		Investigative	Drug Info
Pathway Response	Autophagy			hsa04140
Cell Process	Cellular Processes
	Cellular Transport
	Cellular catabolism
	Cell autophagy
In-vitro Model	Tcam-2/DDP (Cisplatin-resistant TCam-2 cell line)
	TCam-2	Testicular seminoma	Homo sapiens	CVCL_T012

Obesity [ICD-11: 5B81]

Disease Info

In total 2 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response				[5]
Response Summary	Autophagy protein 5 (ATG5) and 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 (Fto^flox/flox) and adipose-selective fto knockout (Fabp4-Cre Fto^flox/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				[5]
Response Summary	Autophagy protein 5 (ATG5) and 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 (Fto^flox/flox) and adipose-selective fto knockout (Fabp4-Cre Fto^flox/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).

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 Autophagy protein 5 (ATG5), 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).

Cisplatin [Approved]

Drug Info

In total 1 item(s) under this drug
Experiment 1 Reporting the m6A-centered Drug Response				[4]
Response Summary	m6A methyltransferase METTL3 regulates autophagy and sensitivity to cisplatin by targeting Autophagy protein 5 (ATG5) in seminoma. The use of autophagy inhibitors 3-MA could reverse the protective effect of METTL3 on TCam-2 cells.
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Responsed Disease	Testicular cancer		ICD-11: 2C80	Disease Info
Pathway Response	Autophagy			hsa04140
Cell Process	Cellular Processes
	Cellular Transport
	Cellular catabolism
	Cell autophagy
In-vitro Model	Tcam-2/DDP (Cisplatin-resistant TCam-2 cell line)
	TCam-2	Testicular seminoma	Homo sapiens	CVCL_T012

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 Autophagy protein 5 (ATG5), 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, Autophagy protein 5 (ATG5), 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, Autophagy protein 5 (ATG5), 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 Autophagy protein 5 (ATG5), 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).

3-Methyladenine [Investigative]

Drug Info

In total 1 item(s) under this drug
Experiment 1 Reporting the m6A-centered Drug Response				[4]
Response Summary	m6A methyltransferase METTL3 regulates autophagy and sensitivity to cisplatin by targeting Autophagy protein 5 (ATG5) in seminoma. The use of autophagy inhibitors 3-MA could reverse the protective effect of METTL3 on TCam-2 cells.
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Responsed Disease	Testicular cancer		ICD-11: 2C80	Disease Info
Pathway Response	Autophagy			hsa04140
Cell Process	Cellular Processes
	Cellular Transport
	Cellular catabolism
	Cell autophagy
In-vitro Model	Tcam-2/DDP (Cisplatin-resistant TCam-2 cell line)
	TCam-2	Testicular seminoma	Homo sapiens	CVCL_T012

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	The m6A methyltransferase METTL3 regulates autophagy and sensitivity to cisplatin by targeting ATG5 in seminoma. Transl Androl Urol. 2021 Apr;10(4):1711-1722. doi: 10.21037/tau-20-1411.
Ref 5	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.
Ref 6	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.

m6A Target Gene Information

Cite M6AREG

Correspondence

Prof. Feng ZHU

Prof. Shuiping Liu

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