Name	Liver cancer
ICD	ICD-11: 2C12

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[1]
Response Summary	The N6-methyladenosine (m6A) modification of ASPM mRNA mediated by METTL3 promoted its expression in liver hepatocellular carcinoma.
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Cell Process	Cells growth
	Cell metastasis
In-vitro Model	SNU-449	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0454
	MHCC97-H	Adult hepatocellular carcinoma	Homo sapiens	CVCL_4972
	Hepg3b (Hepg3b were purchased from the American Type Culture Collection (ATCC, USA))
	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[2]
Response Summary	WTAP/LKB1/AMPK subunit alpha-1 (AMPK/PRKAA1) axis in hepatocellular carcinoma cells acted as a key regulator, linking m6A with autophagy. WTAP-mediated m6A modification plays an important role in the regulation of autophagy in hepatocellular carcinoma cells, which provides a promising target for the treatment of hepatocellular carcinoma.
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulator	Wilms tumor 1-associating protein (WTAP)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	AMPK signaling pathway			hsa04152
	Autophagy			hsa04140
Cell Process	Cell autophagy
In-vitro Model	BEL-7402	Endocervical adenocarcinoma	Homo sapiens	CVCL_5492
	BEL-7404	Endocervical adenocarcinoma	Homo sapiens	CVCL_6568
	HEK293T	Normal	Homo sapiens	CVCL_0063
	L-02	Endocervical adenocarcinoma	Homo sapiens	CVCL_6926
	SMMC-7721	Endocervical adenocarcinoma	Homo sapiens	CVCL_0534

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[3]
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]
Responsed Drug	Sorafenib		Approved	Drug Info
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	FoxO signaling pathway			hsa04068
	Autophagy			hsa04140
Cell Process	Cell autophagy
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[3]
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]
Responsed Drug	Sorafenib		Approved	Drug Info
Target Regulator	YTH domain-containing family protein 1 (YTHDF1)		READER	Regulator Info
Target Regulation	Up regulation
Pathway Response	FoxO signaling pathway			hsa04068
	Autophagy			hsa04140
Cell Process	Cell autophagy

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[3]
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, ATG7, ATG12, and Autophagy-related protein 16-1 (ATG16L1).
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Responsed Drug	Sorafenib		Approved	Drug Info
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	FoxO signaling pathway			hsa04068
	Autophagy			hsa04140
Cell Process	Cell autophagy
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[3]
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, ATG7, ATG12, and Autophagy-related protein 16-1 (ATG16L1).
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Responsed Drug	Sorafenib		Approved	Drug Info
Target Regulator	YTH domain-containing family protein 1 (YTHDF1)		READER	Regulator Info
Target Regulation	Up regulation
Pathway Response	FoxO signaling pathway			hsa04068
	Autophagy			hsa04140
Cell Process	Cell autophagy

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[4]
Response Summary	HIF-1-alpha-induced YTHDF1 expression was associated with hypoxia-induced autophagy and autophagy-related hepatocellular carcinoma progression via promoting translation of autophagy-related genes Autophagy-related protein 2 homolog A (ATG2A) and ATG14 in a m6A-dependent manner.
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulator	YTH domain-containing family protein 1 (YTHDF1)		READER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Autophagy			hsa04140
	HIF-1 signaling pathway			hsa04066
Cell Process	Cell proliferation
	Cell migration
	Cell invasion
	Cell autophagy
In-vitro Model	Hep 3B2.1-7	Childhood hepatocellular carcinoma	Homo sapiens	CVCL_0326
	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
	Huh-7	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0336
	SMMC-7721	Endocervical adenocarcinoma	Homo sapiens	CVCL_0534
In-vivo Model	HCC cells (1 × 106/100 uL PBS) were administered to 4-week-old female BALB/c nude mice by subcutaneous injection (n = 6).

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[4]
Response Summary	HIF-1-alpha-induced YTHDF1 expression was associated with hypoxia-induced autophagy and autophagy-related hepatocellular carcinoma progression via promoting translation of autophagy-related genes ATG2A and Beclin 1-associated autophagy-related key regulator (ATG14) in a m6A-dependent manner.
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulator	YTH domain-containing family protein 1 (YTHDF1)		READER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Autophagy			hsa04140
	HIF-1 signaling pathway			hsa04066
Cell Process	Cell proliferation
	Cell migration
	Cell invasion
	Cell autophagy
In-vitro Model	Hep 3B2.1-7	Childhood hepatocellular carcinoma	Homo sapiens	CVCL_0326
	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
	Huh-7	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0336
	SMMC-7721	Endocervical adenocarcinoma	Homo sapiens	CVCL_0534
In-vivo Model	HCC cells (1 × 106/100 uL PBS) were administered to 4-week-old female BALB/c nude mice by subcutaneous injection (n = 6).

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[5]
Response Summary	Analyzed the effect of sorafenib on HSC ferroptosis and m6A modification in advanced fibrotic patients with hepatocellular carcinoma receiving sorafenib monotherapy. YTHDF1 promotes Beclin-1 (BECN1) mRNA stability and autophagy activation via recognizing the m6A binding site within BECN1 coding regions.
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Responsed Drug	Sorafenib		Approved	Drug Info
Target Regulator	YTH domain-containing family protein 1 (YTHDF1)		READER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Ferroptosis			hsa04216
	Autophagy			hsa04140
Cell Process	Ferroptosis
	Cell autophagy
In-vitro Model	HSC (Hematopoietic stem cell)
In-vivo Model	VA-Lip-Mettl4-shRNA, VA-Lip-Fto-Plasmid and VA-Lip-Ythdf1-shRNA (0.75 mg/kg) were injected intravenously 3 times a week.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[6]
Response Summary	METTL3 is significantly up-regulated in Hepatoblastoma(HB) and promotes HB development.m6A mRNA methylation contributes significantly to regulate the Wnt/beta-catenin pathway. Reduced m6A methylation can lead to a decrease in expression and stability of the Catenin beta-1 (CTNNB1/Beta-catenin).
Responsed Disease	Hepatoblastoma [ICD-11: 2C12.01]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Wnt signaling pathway			hsa04310
Cell Process	RNA stability
In-vitro Model	HEK293T	Normal	Homo sapiens	CVCL_0063
	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
	L-02	Endocervical adenocarcinoma	Homo sapiens	CVCL_6926
	QSG-7701	Endocervical adenocarcinoma	Homo sapiens	CVCL_6944
In-vivo Model	5 × 106 cells were subcutaneously injected into the left or right flank of each mouse.

In total 4 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[7]
Response Summary	Cellular tumor antigen p53 (TP53/p53) n6-methyladenosine (m6A) played a decisive role in regulating Hepatocellular carcinoma(HCC) sensitivity to chemotherapy via the p53 activator RG7112 and the vascular endothelial growth factor receptor inhibitor apatinib. p53 mRNA m6A modification blockage induced by S-adenosyl homocysteine or siRNA-mediated METTL3 inhibition enhanced HCC sensitivity to chemotherapy.
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Responsed Drug	Apatinib		Approved	Drug Info
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	p53 signaling pathway			hsa04115
	Apoptosis			hsa04210
Cell Process	Cell apoptosis
In-vitro Model	QGY-7701	Human papillomavirus-related endocervical adenocarcinoma	Homo sapiens	CVCL_6859
	HHL-5	Normal	Homo sapiens	CVCL_S956
	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
In-vivo Model	Nude mice (4-6 week-old) were administered sterile water and feed in a specific pathogen-free barrier. Using a 1-mL syringe, 1 × 107 HEPG2 cells were subcutaneously inoculated into the right axilla of nude mice to build the HCC xenograft model. When the tumor volume reached 50 mm3, the nude mice were randomly divided into 1 control (n = 4) and 3 treatment groups (n = 4 each). RG7112, apatinib, and RG7112 + apatinib were administered to the treatment groups and an equal volume of dimethyl sulfoxide to the control group by daily gavage for 14 d. The tumor length (L) and width (W) were measured on alternate days using vernier calipers. The following formula was used to calculate the tumor volume: volume (mm3) = 0.5 × L × W × W. At the end of the experiment, the nude mice were killed by CO2 overdose anesthesia. The tumors were dissected and weighed using a precision balance, and the tumor tissue was stored in liquid nitrogen for further analysis.
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[7]
Response Summary	Cellular tumor antigen p53 (TP53/p53) n6-methyladenosine (m6A) played a decisive role in regulating Hepatocellular carcinoma(HCC) sensitivity to chemotherapy via the p53 activator RG7112 and the vascular endothelial growth factor receptor inhibitor apatinib. p53 mRNA m6A modification blockage induced by S-adenosyl homocysteine or siRNA-mediated METTL3 inhibition enhanced HCC sensitivity to chemotherapy.
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Responsed Drug	RG7112		Phase 1	Drug Info
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	p53 signaling pathway			hsa04115
	Apoptosis			hsa04210
Cell Process	Cell apoptosis
In-vitro Model	QGY-7701	Human papillomavirus-related endocervical adenocarcinoma	Homo sapiens	CVCL_6859
	HHL-5	Normal	Homo sapiens	CVCL_S956
	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
In-vivo Model	Nude mice (4-6 week-old) were administered sterile water and feed in a specific pathogen-free barrier. Using a 1-mL syringe, 1 × 107 HEPG2 cells were subcutaneously inoculated into the right axilla of nude mice to build the HCC xenograft model. When the tumor volume reached 50 mm3, the nude mice were randomly divided into 1 control (n = 4) and 3 treatment groups (n = 4 each). RG7112, apatinib, and RG7112 + apatinib were administered to the treatment groups and an equal volume of dimethyl sulfoxide to the control group by daily gavage for 14 d. The tumor length (L) and width (W) were measured on alternate days using vernier calipers. The following formula was used to calculate the tumor volume: volume (mm3) = 0.5 × L × W × W. At the end of the experiment, the nude mice were killed by CO2 overdose anesthesia. The tumors were dissected and weighed using a precision balance, and the tumor tissue was stored in liquid nitrogen for further analysis.
Experiment 3 Reporting the m6A-centered Disease Response by This Target Gene				[8]
Response Summary	Deletion of METTL16 or ALKBH5 predicted poor OS and DFS of hepatocellular carcinoma (HCC) patients. And this study found significant associations between the genetic alterations and clinicopathological features as well as Cellular tumor antigen p53 (TP53/p53) alteration.
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulator	Methyltransferase-like 16 (METTL16)		WRITER	Regulator Info
Experiment 4 Reporting the m6A-centered Disease Response by This Target Gene				[8]
Response Summary	Deletion of METTL16 or ALKBH5 predicted poor OS and DFS of hepatocellular carcinoma (HCC) patients. And this study found significant associations between the genetic alterations and clinicopathological features as well as Cellular tumor antigen p53 (TP53/p53) alteration.
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulator	RNA demethylase ALKBH5 (ALKBH5)		ERASER	Regulator Info

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[9]
Response Summary	The role of YTHDF2 in tumourigenesis and cisplatin-desensitising function by promoting the degradation of Cyclin-dependent kinase inhibitor 1B (CDKN1B/p27) mRNA in an m6 A-dependent manner. YTHDF2 exhibits tumour oncogenic and cisplatin-desensitising properties, which offer insight into the development of novel combination therapeutic strategies for intrahepatic cholangiocarcinoma.
Responsed Disease	Intrahepatic cholangiocarcinoma [ICD-11: 2C12.10]
Responsed Drug	Cisplatin		Approved	Drug Info
Target Regulator	YTH domain-containing family protein 2 (YTHDF2)		READER	Regulator Info
Target Regulation	Down regulation
Pathway Response	Cell cycle			hsa04110
Cell Process	Cell proliferation
	Arrest cell cycle at G0/G1 phase
In-vitro Model	HuCC-T1	Intrahepatic cholangiocarcinoma	Homo sapiens	CVCL_0324
	RBE	Intrahepatic cholangiocarcinoma	Homo sapiens	CVCL_4896
	HCCC-9810 (The intrahepatic cholangiocarcinoma cell lines (HCCC-9810) were purchased from Cellcook Co., Ltd. (Guangzhou, China).)
	HIBEC (The normal intrahepatic bile duct cell line (HIBEC) were purchased from Cellcook Co., Ltd. (Guangzhou, China).)
In-vivo Model	For tumour xenograft models, 1 × 107 HuCC-T1 cells in knockdown group or control group were implanted into the right flank of 5-week-old female nude mice. The volumes of tumour were recorded every 4 days by calliper. The volumes were calculated as length × width2/2. For patient-derived xenograft (PDX) model (PDX0075), ICC tissues from a patient, who relapsed in 6 months after R0 resection and subsequent chemotherapy with cisplatin and gemcitabine, were diced into 3 mm3 pieces and transplanted subcutaneously into the right flank of 5-week-old female B-NDG mice.

In total 3 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[10]
Response Summary	METTL3-mediated Cystine/glutamate transporter (SLC7A11) m6A modification enhances hepatoblastoma ferroptosis resistance. The METTL3/IGF2BP1/m6A modification promotes SLC7A11 mRNA stability and upregulates its expression by inhibiting the deadenylation process.
Responsed Disease	Hepatoblastoma [ICD-11: 2C12.01]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Ferroptosis			hsa04216
Cell Process	Ferroptosis
In-vitro Model	HuH-6	Hepatoblastoma	Homo sapiens	CVCL_4381
	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
	HEK293T	Normal	Homo sapiens	CVCL_0063
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[10]
Response Summary	METTL3-mediated Cystine/glutamate transporter (SLC7A11) m6A modification enhances hepatoblastoma ferroptosis resistance. The METTL3/IGF2BP1/m6A modification promotes SLC7A11 mRNA stability and upregulates its expression by inhibiting the deadenylation process.
Responsed Disease	Hepatoblastoma [ICD-11: 2C12.01]
Target Regulator	Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1)		READER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Ferroptosis			hsa04216
Cell Process	Ferroptosis
In-vitro Model	HuH-6	Hepatoblastoma	Homo sapiens	CVCL_4381
	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
	HEK293T	Normal	Homo sapiens	CVCL_0063
Experiment 3 Reporting the m6A-centered Disease Response by This Target Gene				[11]
Response Summary	METTL14 induced m6A modification at 5'UTR of Cystine/glutamate transporter (SLC7A11) mRNA, which in turn underwent degradation relied on the YTHDF2-dependent pathway. Identify the HIF-1alpha /METTL14/YTHDF2/SLC7A11 axis as a potential therapeutic target for the HCC interventional embolization treatment.
Responsed Disease	Liver cancer [ICD-11: 2C12]
Target Regulator	Methyltransferase-like 14 (METTL14)		WRITER	Regulator Info
Target Regulation	Down regulation
Pathway Response	HIF-1 signaling pathway			hsa04066
Cell Process	RNA stability
In-vitro Model	PLC/PRF/5	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0485
	MHCC97-H	Adult hepatocellular carcinoma	Homo sapiens	CVCL_4972
	L-02	Endocervical adenocarcinoma	Homo sapiens	CVCL_6926
	Huh-7	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0336
	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
	HCCLM3	Adult hepatocellular carcinoma	Homo sapiens	CVCL_6832
	BEL-7402	Endocervical adenocarcinoma	Homo sapiens	CVCL_5492
	7721 (Human hepatic malignant cell line)
In-vivo Model	For the subcutaneous implantation model, 5 × 105 stable SLC7A11-knockdown HCCLM3 cells or SLC7A11-vector cells were injected subcutaneously into BALB/C nude mice.

In total 3 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[12]
Response Summary	In the Hepatocellular carcinoma cells YTHDC2 promotes CYP2C8 mRNA degradation via recognizing the m6A in CYP2C8 mRNA, which is installed by METTL3/14 and removed by FTO.
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulator	YTH domain-containing protein 2 (YTHDC2)		READER	Regulator Info
Target Regulation	Down regulation
Pathway Response	Drug metabolism - cytochrome P450			hsa00982
Cell Process	Drug-metabolizing
In-vitro Model	HepaRG	Hepatitis C infection	Homo sapiens	CVCL_9720
	Huh-7	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0336
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[12]
Response Summary	In the Hepatocellular carcinoma cells YTHDC2 promotes CYP2C8 mRNA degradation via recognizing the m6A in CYP2C8 mRNA, which is installed by METTL3/14 and removed by FTO.
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Drug metabolism - cytochrome P450			hsa00982
Cell Process	Drug-metabolizing
In-vitro Model	HepaRG	Hepatitis C infection	Homo sapiens	CVCL_9720
	Huh-7	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0336
Experiment 3 Reporting the m6A-centered Disease Response by This Target Gene				[12]
Response Summary	In the Hepatocellular carcinoma cells YTHDC2 promotes CYP2C8 mRNA degradation via recognizing the m6A in CYP2C8 mRNA, which is installed by METTL3/14 and removed by FTO.
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulator	Fat mass and obesity-associated protein (FTO)		ERASER	Regulator Info
Target Regulation	Down regulation
Pathway Response	Drug metabolism - cytochrome P450			hsa00982
Cell Process	Drug-metabolizing
In-vitro Model	HepaRG	Hepatitis C infection	Homo sapiens	CVCL_9720
	Huh-7	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0336

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[13]
Response Summary	KIAA1429 facilitated migration and invasion of Hepatocellular carcinoma cells by inhibiting DNA-binding protein inhibitor ID-2 (ID2) via upregulating m6A modification of ID2 mRNA.
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulator	Protein virilizer homolog (VIRMA)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	RNA degradation			hsa03018
Cell Process	Cell migration and invasion
In-vitro Model	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
	Hep-G2/2.2.15	Hepatoblastoma	Homo sapiens	CVCL_L855
	L-02	Endocervical adenocarcinoma	Homo sapiens	CVCL_6926
	Huh-7	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0336

In total 4 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[14]
Response Summary	YTHDF2 acts as a tumor suppressor to repress cell proliferation and growth via destabilizing the Epidermal growth factor receptor (EGFR) mRNA in HCC.
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulator	YTH domain-containing family protein 2 (YTHDF2)		READER	Regulator Info
Target Regulation	Down regulation
Pathway Response	MAPK signaling pathway			hsa04010
Cell Process	Glucose metabolism
In-vitro Model	BEL-7402	Endocervical adenocarcinoma	Homo sapiens	CVCL_5492
	Hep 3B2.1-7	Childhood hepatocellular carcinoma	Homo sapiens	CVCL_0326
	QGY-7703	Endocervical adenocarcinoma	Homo sapiens	CVCL_6715
	SMMC-7721	Endocervical adenocarcinoma	Homo sapiens	CVCL_0534
In-vivo Model	5 × 106 of HEP3B and SMMC7721 stable cells were resuspended in 0.1 ml of PBS and subcutaneously injected into the flank of mice.
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[15]
Response Summary	YTHDF1 regulates the translation of Epidermal growth factor receptor (EGFR) mRNA via binding m6 A sites in the 3'-UTR of EGFR transcript. YTHDF1 is upregulated in ICC and associated with shorter survival of ICC patients.
Responsed Disease	Intrahepatic cholangiocarcinoma [ICD-11: 2C12.10]
Target Regulator	YTH domain-containing family protein 1 (YTHDF1)		READER	Regulator Info
Target Regulation	Up regulation
Pathway Response	PI3K-Akt signaling pathway			hsa04151
Cell Process	Cell proliferation
	Cell migration
	Cell nvasion
In-vitro Model	HuCC-T1	Intrahepatic cholangiocarcinoma	Homo sapiens	CVCL_0324
	RBE	Intrahepatic cholangiocarcinoma	Homo sapiens	CVCL_4896
In-vivo Model	For the subcutaneous implantation ICC mouse model, 6-week-old male NCG mice (Jiangsu, China) were randomly enrolled into shNC group and shYTHDF1 group (n = 9); 1 × 106 HuCCT1 cells in 0.1-mL PBS transfected with shNC or shYTHDF1 were subcutaneously inoculated in the right flanks of the mice. For AKT/YapS127A-induced orthotopic ICC mouse model, 16 mice were divided into two groups randomly. For the control group, 20-ug AKT, 30-ug Yap, and 2-ug pCMV/SB plasmids plus 20-ug vector plasmids as control were diluted in 2-mL saline and then were injected into the lateral tail vein within 7 s. For the YTHDF1-overexpressed group, mice were injected with additional 20-ug YTHDF1 plasmids under the same conditions. Mice were sacrificed at 4 weeks after injection, and liver tissues were harvested for analysis.
Experiment 3 Reporting the m6A-centered Disease Response by This Target Gene				[16]
Response Summary	Sublethal heat treatment increases epidermal factor growth receptor (EGFR) m6A modification in the vicinity of the 5' untranslated region and promotes its binding with YTHDF1, which enhances the translation of Epidermal growth factor receptor (EGFR) mRNA. Combination of YTHDF1 silencing and EGFR inhibition suppressed the malignancies of HCC cells synergically.
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulator	YTH domain-containing family protein 1 (YTHDF1)		READER	Regulator Info
Target Regulation	Up regulation
Pathway Response	mRNA surveillance pathway			hsa03015), RNA degradation
Cell Process	RNA stability
In-vivo Model	The caudal vein injection mouse model, intrasplenic injection mouse model, and orthotopic xenograft IRFA HCC mouse models, including patient-derived xenograft (PDX), and cell-line-derived xenograft implantation models, were established as reported.
Experiment 4 Reporting the m6A-centered Disease Response by This Target Gene				[17]
Response Summary	METTL14 was found to inhibit HCC cell migration, invasion, and EMT through modulating Epidermal growth factor receptor (EGFR)/PI3K/AKT signaling pathway in an m6A-dependent manner.
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulator	Methyltransferase-like 14 (METTL14)		WRITER	Regulator Info
Target Regulation	Down regulation
Pathway Response	PI3K-Akt signaling pathway			hsa04151
Cell Process	Epithelial-mesenchymal transition
In-vitro Model	YY-8103	Adult hepatocellular carcinoma	Homo sapiens	CVCL_WY40
	SMMC-7721	Endocervical adenocarcinoma	Homo sapiens	CVCL_0534
	HCCLM3	Adult hepatocellular carcinoma	Homo sapiens	CVCL_6832
	L-02	Endocervical adenocarcinoma	Homo sapiens	CVCL_6926
	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
	Hep 3B2.1-7	Childhood hepatocellular carcinoma	Homo sapiens	CVCL_0326
In-vivo Model	For the lung metastasis model, stably transfected HepG2 cells (1 × 106/0.1 mL DMEM) were injected into each nude mouse through the tail vein. Five weeks later, mice were euthanized, and the lung tissues were collected.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[18]
Response Summary	In contrast to the mRNA-decay-promoting function of YTH domain-containing family protein 2, IGF2BPs promote the stability and storage of their target mRNAs (for example, MYC) in an m6A-dependent manner under normal and stress conditions and therefore affect gene expression output. Four representative high confidence targets, including MYC, Fascin (FSCN1), TK1, and MARCKSL1, exhibit strong binding with IGF2BPs around their m6A motifs in control cells. Knocking down of each individual IGF2BPs in Hela (cervical cancer) and HepG2 (liver cancer) cells significantly repressed MYC expression.
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulator	Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1)		READER	Regulator Info
Cell Process	RNA decay
In-vitro Model	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
	HEK293T	Normal	Homo sapiens	CVCL_0063
	HeLa	Endocervical adenocarcinoma	Homo sapiens	CVCL_0030
	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[19]
Response Summary	IGF2BP2 overexpression promoted HCC proliferation in vitro and in vivo, IGF2BP2 directly recognized and bound to the m6A site on FEN1 mRNA and enhanced Flap endonuclease 1 (FEN1) mRNA stability.
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulator	Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2)		READER	Regulator Info
Target Regulation	Up regulation
In-vitro Model	PLC/PRF/5	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0485
	MHCC97-L	Adult hepatocellular carcinoma	Homo sapiens	CVCL_4973
	Huh-7	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0336
	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
In-vivo Model	A total of 40 BALB/c nude mice were chosen and assigned to two groups: shCtrl group (injected with HepG2 cells) and shIGF2BP2 group (injected with HepG2 cells with IGF2BP2 knockdown). 200 ul of the above cell suspension containing 2 × 105 cells was injected into the left or right back of each mice.

In total 3 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[20]
Response Summary	METTL3 and Forkhead box protein O3 (FOXO3) levels are tightly correlated in hepatocellular carcinoma patients. In mouse xenograft models, METTL3 depletion significantly enhances sorafenib resistance of HCC by abolishing the identified METTL3-mediated FOXO3 mRNA stabilization, and overexpression of FOXO3 restores m6 A-dependent sorafenib sensitivity.
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Responsed Drug	Sorafenib		Approved	Drug Info
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Down regulation
Pathway Response	FoxO signaling pathway			hsa04068
Cell Process	Cell Transport
	Cell catabolism
	Cell autophagy
In-vitro Model	HEK293T	Normal	Homo sapiens	CVCL_0063
	Hepa 1-6	Hepatocellular carcinoma of the mouse	Mus musculus	CVCL_0327
	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
	HUVEC-C	Normal	Homo sapiens	CVCL_2959
	WRL 68	Endocervical adenocarcinoma	Homo sapiens	CVCL_0581
In-vivo Model	For the drug-resistant subcutaneous tumor models, drug administration was adopted when the tumors reached about 50 mm3 in size, at which point mice were randomized for treatment with DMSO(intraperitoneally) or sorafenib (50 mg/kg/every 2 days, intraperitoneally). For the patient-derived tumor xenograft model, drug administration began 4 weeks after tumors reached about 100 mm3 in size with sorafenib (50 mg/kg/every 3 days, intraperitoneally) or siCtrl/siMETTL3 intratumor injection.
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[3]
Response Summary	METTL3 can sensitise hepatocellular carcinoma cells to sorafenib through stabilising Forkhead box protein O3 (FOXO3) in an m6A-dependent manner and translated by YTHDF1, thereby inhibiting the transcription of autophagy-related genes, including ATG3, ATG5, ATG7, ATG12, and ATG16L1.
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Responsed Drug	Sorafenib		Approved	Drug Info
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	FoxO signaling pathway			hsa04068
Cell Process	Cell autophagy
Experiment 3 Reporting the m6A-centered Disease Response by This Target Gene				[3]
Response Summary	METTL3 can sensitise hepatocellular carcinoma cells to sorafenib through stabilising Forkhead box protein O3 (FOXO3) in an m6A-dependent manner and translated by YTHDF1, thereby inhibiting the transcription of autophagy-related genes, including ATG3, ATG5, ATG7, ATG12, and ATG16L1.
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Responsed Drug	Sorafenib		Approved	Drug Info
Target Regulator	YTH domain-containing family protein 1 (YTHDF1)		READER	Regulator Info
Target Regulation	Up regulation
Pathway Response	FoxO signaling pathway			hsa04068
Cell Process	Cell autophagy

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[21]
Response Summary	YTHDF2 processed the decay of m6A-containing interleukin 11 (IL11) and Glia-derived nexin (SERPINE2) mRNAs. YTHDF2 transcription succumbed to hypoxia-inducible factor-2-alpha (HIF-2-alpha). Administration of a HIF-2-alpha antagonist (PT2385) restored YTHDF2-programed epigenetic machinery and repressed liver cancer.
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulator	YTH domain-containing family protein 2 (YTHDF2)		READER	Regulator Info
Target Regulation	Down regulation
Pathway Response	HIF-1 signaling pathway			hsa04066
Cell Process	Biological regulation
In-vitro Model	MHCC97-H	Adult hepatocellular carcinoma	Homo sapiens	CVCL_4972
	SMMC-7721	Endocervical adenocarcinoma	Homo sapiens	CVCL_0534
In-vivo Model	A number of 5 × 106 SMMC7721 or MHCC97H cells re-suspended in 100 uL of PBS were subcutaneously injected into the right flank of 6-week old male NCG mice.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[22]
Response Summary	CircMEG3 inhibits the expression of m6A methyltransferase METTL3 dependent on HULC. Moreover, CircMEG3 inhibits the expression of H/ACA ribonucleoprotein complex subunit DKC1 (DKC1), a component of telomere synthetase H/ACA ribonucleoprotein (RNP; catalyst RNA pseudouracil modification) through METTL3 dependent on HULC. These observations provide important basic information for finding effective liver cancer therapeutic targets.
Responsed Disease	Liver cancer [ICD-11: 2C12]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Down regulation
In-vitro Model	Huh-7	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0336
In-vivo Model	Athymic BALB/c mice were injected with LCSC cells at the armpit area subcutaneously. The mice were then sacrificed and the tumors recovered.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[23]
Response Summary	The Hepatocyte nuclear factor 3-gamma (HNF3gamma/FOXA3) reduction in hepatocellular carcinoma could be mediated by METTL14-dependent m6A methylation of HNF3-Gamma mRNA. HNF3-Gamma plays an essential role in HCC differentiation and serves as a therapeutic target and predictor of sorafenib benefit in patients.
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Responsed Drug	Sorafenib		Approved	Drug Info
Target Regulator	Methyltransferase-like 14 (METTL14)		WRITER	Regulator Info
Target Regulation	Down regulation
Cell Process	Membrane transport
	Cell apoptosis
In-vitro Model	HCCLM3	Adult hepatocellular carcinoma	Homo sapiens	CVCL_6832
	Huh-7	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0336
In-vivo Model	When xenografted tumor growth reached 500 mm3, the mice were subjected to intratumoral injection of Ad-con or Ad-HNF3γ every other day. For the PDX model, fresh patient HCC tissues were cut into fragments with a volume of 3 × 3 mm3 and then implanted subcutaneously into the flanks of nude mice. The mice were given sorafenib (30 mg/kg) or vehicle orally twice a week for 24 days.

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[24]
Response Summary	In hepatocellular carcinoma, METTL3 could direct the formation of circHPS5, and specific m6A controlled the accumulation of circHPS5. YTHDC1 facilitated the cytoplasmic output of circHPS5 under m6A modification. CircHPS5 can act as a miR-370 sponge to regulate the expression of High mobility group protein HMGI-C (HMGA2) and further accelerate hepatocellular carcinoma cell tumorigenesis.
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Transcriptional misregulation in cancer			hsa05202
Cell Process	Epithelial-mesenchymal transition
	Cell autophagy
In-vitro Model	Hep 3B2.1-7	Childhood hepatocellular carcinoma	Homo sapiens	CVCL_0326
	L-02	Endocervical adenocarcinoma	Homo sapiens	CVCL_6926
In-vivo Model	To create the xenograft neoplasm system, 40 male BALB/c nude mice aged 5 weeks were randomly separated into sh-NC, sh-circHPS5, sh-circHPS5+CTRL, and sh-circHPS5+SAH groups (n = 5 for each group). HCC cells were subcutaneously injected into the axilla of the nude mice.
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[24]
Response Summary	In hepatocellular carcinoma, METTL3 could direct the formation of circHPS5, and specific m6A controlled the accumulation of circHPS5. YTHDC1 facilitated the cytoplasmic output of circHPS5 under m6A modification. CircHPS5 can act as a miR-370 sponge to regulate the expression of High mobility group protein HMGI-C (HMGA2) and further accelerate hepatocellular carcinoma cell tumorigenesis.
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulator	YTH domain-containing protein 1 (YTHDC1)		READER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Transcriptional misregulation in cancer			hsa05202
Cell Process	Epithelial-mesenchymal transition
	Cell autophagy
In-vitro Model	Hep 3B2.1-7	Childhood hepatocellular carcinoma	Homo sapiens	CVCL_0326
	L-02	Endocervical adenocarcinoma	Homo sapiens	CVCL_6926
In-vivo Model	To create the xenograft neoplasm system, 40 male BALB/c nude mice aged 5 weeks were randomly separated into sh-NC, sh-circHPS5, sh-circHPS5+CTRL, and sh-circHPS5+SAH groups (n = 5 for each group). HCC cells were subcutaneously injected into the axilla of the nude mice.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[25]
Response Summary	HBXIP drives metabolic reprogramming in hepatocellular carcinoma cells via METTL3-mediated m6A modification of Hypoxia-inducible factor 1-alpha (HIF-1-Alpha/HIF1A). Highly expressed HBXIP and METTL3 are associated with dismal oncologic outcomes of patients with hepatocellular carcinoma. The positive relation between HBXIP and METTL3 can activate reprogramming of HCC cell metabolism by inducing m6A modification of HIF-1-alpha, which is unraveled to enhance aggressive biological behaviors of HCC cells.
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	HIF-1 signaling pathway			hsa04066
	Central carbon metabolism in cancer			hsa05230
Cell Process	Glycolysis
	Glutaminolysis
In-vitro Model	BEL-7402	Endocervical adenocarcinoma	Homo sapiens	CVCL_5492
	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
	L-02	Endocervical adenocarcinoma	Homo sapiens	CVCL_6926
	MHCC97	Adult hepatocellular carcinoma	Homo sapiens	CVCL_4971
	SMMC-7721	Endocervical adenocarcinoma	Homo sapiens	CVCL_0534

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[26]
Response Summary	KDM5B regulates the YTHDF3/ITGA6 axis by inhibiting the expression of miR-448 to promote the occurrence of hepatocellular carcinoma. miR-448 could target YTHDF3 and inhibit the YTHDF3/Integrin alpha-6 (ITGA6) axis, thereby inhibiting the occurrence of HCC.
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulator	YTH domain-containing family protein 3 (YTHDF3)		READER	Regulator Info
Cell Process	Cell proliferation
	Cell migration
	Cell invasion
	Cell apoptosis
In-vitro Model	HEK293T	Normal	Homo sapiens	CVCL_0063
	Hep 3B2.1-7	Childhood hepatocellular carcinoma	Homo sapiens	CVCL_0326
	SMMC-7721	Endocervical adenocarcinoma	Homo sapiens	CVCL_0534
In-vivo Model	HCC cells (5 × 106 cells/mouse) that had been transfected with oe-NC + sh-NC, oe-KDM5B + sh-NC, or oe-KDM5B + sh-ITGA6, or treated with NS, GSK-467 (a selective inhibitor of KDM5B) + oe-NC or GSK-467 + oe-ITGA6 were then subcutaneously implanted into the back of mice.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[27]
Response Summary	METTL3 was upregulated and predicted poor prognosis of patients with intrahepatic cholangiocarcinoma(ICC). H3K4me3 activation-driven METTL3 transcription promotes ICC progression by YTHDF2-mediated Interferon-induced 54 kDa protein (IFIT2) mRNA degradation.
Responsed Disease	Intrahepatic cholangiocarcinoma [ICD-11: 2C12.10]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Down regulation
In-vitro Model	HuCC-T1	Intrahepatic cholangiocarcinoma	Homo sapiens	CVCL_0324
	HCCC-9810	Intrahepatic cholangiocarcinoma	Homo sapiens	CVCL_6908
In-vivo Model	4-week-old female BALB/c nude mice were used for HuCC-T1 tumor xenograft models and 4-week-old female B-NDG mice (Biocytogen, Beijing, China) were used for HCCC-9810 tumor xenograft models. 1 × 107 HuCC-T1 or HCCC-9810 cells were resuspended in 100 ul PBS with Matrigel (1:1), and injected into the right flank of mice (n = 6/group).

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[28]
Response Summary	ILF3-AS1 expression was significantly elevated in HCC tissues,mechanistically, ILF3-AS1 associated with Interleukin enhancer-binding factor 3 (ILF3) mRNA and inhibited its degradation. ILF3-AS1 increased ILF3 m6A level via recruiting N6-methyladenosine (m6A) RNA methyltransferase METTL3. Moreover, IFL3-AS1 enhanced the interaction between ILF3 mRNA and m6A reader IGF2BP1.
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
In-vitro Model	Huh-7	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0336
	Hep 3B2.1-7	Childhood hepatocellular carcinoma	Homo sapiens	CVCL_0326
	HEK293T	Normal	Homo sapiens	CVCL_0063
In-vivo Model	Approximately 5 × 106 control and ILF3-AS1 silencing Huh7 cells were subcutaneously implanted into the right flank of nude mice.Xenograft size was measured every 7 days and calculated using the equation V(mm3)=(length×width2)/2. 35 days later, the mice were sacrificed, and the tumor tissues were isolated and weighed.
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[28]
Response Summary	ILF3-AS1 expression was significantly elevated in HCC tissues,mechanistically, ILF3-AS1 associated with Interleukin enhancer-binding factor 3 (ILF3) mRNA and inhibited its degradation. ILF3-AS1 increased ILF3 m6A level via recruiting N6-methyladenosine (m6A) RNA methyltransferase METTL3. Moreover, IFL3-AS1 enhanced the interaction between ILF3 mRNA and m6A reader IGF2BP1.
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulator	Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1)		READER	Regulator Info
Target Regulation	Up regulation
In-vitro Model	Huh-7	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0336
	Hep 3B2.1-7	Childhood hepatocellular carcinoma	Homo sapiens	CVCL_0326
	HEK293T	Normal	Homo sapiens	CVCL_0063
In-vivo Model	Approximately 5 × 106 control and ILF3-AS1 silencing Huh7 cells were subcutaneously implanted into the right flank of nude mice.Xenograft size was measured every 7 days and calculated using the equation V(mm3)=(length×width2)/2. 35 days later, the mice were sacrificed, and the tumor tissues were isolated and weighed.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[21]
Response Summary	YTHDF2 processed the decay of m6A-containing Interleukin-11 (IL11) and serpin family E member 2 (SERPINE2) mRNAs. YTHDF2 transcription succumbed to hypoxia-inducible factor-2-alpha (HIF-2-alpha). Administration of a HIF-2-alpha antagonist (PT2385) restored YTHDF2-programed epigenetic machinery and repressed liver cancer.
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulator	YTH domain-containing family protein 2 (YTHDF2)		READER	Regulator Info
Target Regulation	Down regulation
Pathway Response	HIF-1 signaling pathway			hsa04066
Cell Process	Biological regulation
In-vitro Model	MHCC97-H	Adult hepatocellular carcinoma	Homo sapiens	CVCL_4972
	SMMC-7721	Endocervical adenocarcinoma	Homo sapiens	CVCL_0534
In-vivo Model	A number of 5 × 106 SMMC7721 or MHCC97H cells re-suspended in 100 uL of PBS were subcutaneously injected into the right flank of 6-week old male NCG mice.

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[29]
Response Summary	METTL3/IGF2BP1/Leukocyte surface antigen CD47 (CD47) mediated EMT transition contributes to the incomplete ablation induced metastasis in HCC cells.
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Cell Process	Epithelial-mesenchymal transition
In-vitro Model	Huh-7	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0336
	HCCLM3	Adult hepatocellular carcinoma	Homo sapiens	CVCL_6832
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[29]
Response Summary	METTL3/IGF2BP1/Leukocyte surface antigen CD47 (CD47) mediated EMT transition contributes to the incomplete ablation induced metastasis in HCC cells.
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulator	Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1)		READER	Regulator Info
Target Regulation	Up regulation
Cell Process	Epithelial-mesenchymal transition
In-vitro Model	Huh-7	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0336
	HCCLM3	Adult hepatocellular carcinoma	Homo sapiens	CVCL_6832

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[30]
Response Summary	ALKBH5 suppressed the proliferation and invasion capabilities of HCC cells in vitro and in vivo. Mechanistically, ALKBH5-mediated m6A demethylation led to a post-transcriptional inhibition of Ly6/PLAUR domain-containing protein 1 (LYPD1).
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulator	RNA demethylase ALKBH5 (ALKBH5)		ERASER	Regulator Info
Target Regulation	Down regulation
In-vitro Model	SMMC-7721	Endocervical adenocarcinoma	Homo sapiens	CVCL_0534
	PLC/PRF/5	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0485
	MHCC97-H	Adult hepatocellular carcinoma	Homo sapiens	CVCL_4972
	Huh-7	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0336
	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
	Hep 3B2.1-7	Childhood hepatocellular carcinoma	Homo sapiens	CVCL_0326
	HCCLM3	Adult hepatocellular carcinoma	Homo sapiens	CVCL_6832
	BEL-7402	Endocervical adenocarcinoma	Homo sapiens	CVCL_5492

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[18]
Response Summary	In contrast to the mRNA-decay-promoting function of YTH domain-containing family protein 2, IGF2BPs promote the stability and storage of their target mRNAs (for example, MYC) in an m6A-dependent manner under normal and stress conditions and therefore affect gene expression output. Four representative high confidence targets, including MYC, FSCN1, TK1, and MARCKS-related protein (MARCKSL1), exhibit strong binding with IGF2BPs around their m6A motifs in control cells. Knocking down of each individual IGF2BPs in Hela (cervical cancer) and HepG2 (liver cancer) cells significantly repressed MYC expression.
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulator	Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1)		READER	Regulator Info
Cell Process	RNA decay
In-vitro Model	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
	HEK293T	Normal	Homo sapiens	CVCL_0063
	HeLa	Endocervical adenocarcinoma	Homo sapiens	CVCL_0030
	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[31]
Response Summary	METTL14 interacts with the microprocessor protein Microprocessor complex subunit DGCR8 (DGCR8) and positively modulates the primary microRNA 126 process in an m6 A-dependent manner. microRNA 126 inhibits the repressing effect of METTL14 in Hepatocellular carcinoma metastasis.
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulator	Methyltransferase-like 14 (METTL14)		WRITER	Regulator Info
Target Regulation	Up regulation
Cell Process	Tumor metastasis
In-vitro Model	HCC-1664 cell line (Primary HCC cells)
	Hep 3B2.1-7	Childhood hepatocellular carcinoma	Homo sapiens	CVCL_0326
	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
	SMMC-7721	Endocervical adenocarcinoma	Homo sapiens	CVCL_0534
	SMMC-7721	Endocervical adenocarcinoma	Homo sapiens	CVCL_0534
In-vivo Model	Male athymic BALB/c nude mice (5 weeks old) were used. Subcutaneous tumor growth assays, liver metastasis model, and tail vein injection model were performed as described.Metastases were detected using the IVIS@Lumina II system (Caliper Life Sciences, Hopkinton, MA) 10 minutes after intraperitoneal injection of 4.0 mg luciferin (Gold Biotech) in 50 uL of saline.

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[18]
Response Summary	In contrast to the mRNA-decay-promoting function of YTH domain-containing family protein 2, IGF2BPs promote the stability and storage of their target mRNAs (for example, MYC) in an m6A-dependent manner under normal and stress conditions and therefore affect gene expression output. Four representative high confidence targets, including Myc proto-oncogene protein (MYC), FSCN1, TK1, and MARCKSL1, exhibit strong binding with IGF2BPs around their m6A motifs in control cells. Knocking down of each individual IGF2BPs in Hela (cervical cancer) and HepG2 (liver cancer) cells significantly repressed MYC expression.
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulator	Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1)		READER	Regulator Info
Cell Process	RNA decay
In-vitro Model	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
	HEK293T	Normal	Homo sapiens	CVCL_0063
	HeLa	Endocervical adenocarcinoma	Homo sapiens	CVCL_0030
	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[32]
Response Summary	m6A-related genes have a prognostic value in liver cancer, and the constructed riskscore can identify patients who are high risk and can enable individualized therapy. Gene set enrichment analysis showed that tumorigenic markers, including DNA repair, E2F targets, G2M checkpoint, and Myc proto-oncogene protein (MYC) targets V1, were enriched in Cluster2.
Responsed Disease	Liver cancer [ICD-11: 2C12]

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[33]
Response Summary	Methyltransferase-like 14 (Mettl14)-induced m6A modification participated in the regulation of USP48 in hepatocellular carcinoma by maintaining USP48 mRNA stability. This work uncovers the tumor-suppressive function of the Mettl14-USP48-NAD-dependent protein deacetylase sirtuin-6 (SIRT6) axis via modulation of glycolysis, providing new insights into the critical roles of metabolic activities in HCC and identifying an attractive target for future treatment studies.
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulator	Methyltransferase-like 14 (METTL14)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Ubiquitin mediated proteolysis			hsa04120
	Glycolysis / Gluconeogenesis			hsa00010
Cell Process	Ubiquitination degradation
	Glycolysis
In-vitro Model	BEL-7404	Endocervical adenocarcinoma	Homo sapiens	CVCL_6568
	Huh-7	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0336
	SK-HEP-1	Liver and intrahepatic bile duct epithelial neoplasm	Homo sapiens	CVCL_0525
	SK-HEP-1	Liver and intrahepatic bile duct epithelial neoplasm	Homo sapiens	CVCL_0525
In-vivo Model	Hepatocyte-specific knockout USP48 was obtained by crossing Alb-Cre mice with USP48flox/flox mice.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[17]
Response Summary	METTL14 was found to inhibit HCC cell migration, invasion, and EMT through modulating EGFR/PI3-kinase subunit alpha (PI3k/PIK3CA)/AKT signaling pathway in an m6A-dependent manner.
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulator	Methyltransferase-like 14 (METTL14)		WRITER	Regulator Info
Target Regulation	Down regulation
Pathway Response	PI3K-Akt signaling pathway			hsa04151
Cell Process	Epithelial-mesenchymal transition
In-vitro Model	YY-8103	Adult hepatocellular carcinoma	Homo sapiens	CVCL_WY40
	SMMC-7721	Endocervical adenocarcinoma	Homo sapiens	CVCL_0534
	HCCLM3	Adult hepatocellular carcinoma	Homo sapiens	CVCL_6832
	L-02	Endocervical adenocarcinoma	Homo sapiens	CVCL_6926
	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
	Hep 3B2.1-7	Childhood hepatocellular carcinoma	Homo sapiens	CVCL_0326
In-vivo Model	For the lung metastasis model, stably transfected HepG2 cells (1 × 106/0.1 mL DMEM) were injected into each nude mouse through the tail vein. Five weeks later, mice were euthanized, and the lung tissues were collected.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[34]
Response Summary	YTHDF2 promotes the CSC liver phenotype and cancer metastasis by modulating the m6A methylation of POU domain, class 5, transcription factor 1 (POU5F1) mRNA. YTHDF2 expression is positively correlated with OCT4 expression and m6A levels in the 5'-UTR of OCT4 mRNA in clinical hepatocellular carcinoma specimens.
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulator	YTH domain-containing family protein 2 (YTHDF2)		READER	Regulator Info
Target Regulation	Up regulation
Pathway Response	RNA degradation			hsa03018
Cell Process	Cancer metastasis
In-vitro Model	Hep 3B2.1-7	Childhood hepatocellular carcinoma	Homo sapiens	CVCL_0326
	Huh-7	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0336

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[35]
Response Summary	ALKBH5 as an important m6A demethylase that orchestrates Programmed cell death 1 ligand 1 (CD274/PD-L1) expression in intrahepatic cholangiocarcinoma (ICC).
Responsed Disease	Intrahepatic cholangiocarcinoma [ICD-11: 2C12.10]
Target Regulator	RNA demethylase ALKBH5 (ALKBH5)		ERASER	Regulator Info
Target Regulation	Up regulation
Pathway Response	PD-L1 expression and PD-1 checkpoint pathway in cancer			hsa05235
In-vitro Model	TFK-1	Cholangiocarcinoma	Homo sapiens	CVCL_2214
	RBE	Intrahepatic cholangiocarcinoma	Homo sapiens	CVCL_4896
	LIPF178c (LIPF178c human bile duct cancer cells from China Center for Type Culture Collection (Wuhan, China))
	LIPF155c (LIPF155c human bile duct cancer cells from China Center for Type Culture Collection (Wuhan, China))
	LICCF (LICCF human intrahepatic bile duct cancer cell line from China Center for Type Culture Collection (Wuhan, China))
	HCCC-9810	Intrahepatic cholangiocarcinoma	Homo sapiens	CVCL_6908
In-vivo Model	ICC tumor cells (LIPF178c-shCtrl/shALKBH5) of 5 × 106 were injected into the right flank of NCG mice. Tumor volume was calculated by the formula: volume = ab2/2 (a, the longer axis; b, the shorter axis). T-cell killing assay in vitro was conducted as previously reported (20). PBMCs from healthy donors were activated and expanded as described above. The day before tumor cell injection, PBMC (i.v. 1 × 107 cells) was adoptively transferred to NCG mice via the tail vein. At the end, the PBMC was isolated and subjected to flow cytometry for detecting T-cell percentage.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[36]
Response Summary	Proliferation-associated protein 2G4 (PA2G4) plays a pro-metastatic role by increasing FYN expression through binding with YTHDF2 in HCC. PA2G4 becomes a reliable prognostic marker or therapeutic target for HCC patients.
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulator	YTH domain-containing family protein 2 (YTHDF2)		READER	Regulator Info
Target Regulation	Up regulation
Cell Process	Cell metastatic
In-vitro Model	PLC/PRF/5	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0485
	MHCC97-H	Adult hepatocellular carcinoma	Homo sapiens	CVCL_4972
	Huh-7	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0336
	HLF	Adult hepatocellular carcinoma	Homo sapiens	CVCL_2947
	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
	Hep 3B2.1-7	Childhood hepatocellular carcinoma	Homo sapiens	CVCL_0326
	HEK293T	Normal	Homo sapiens	CVCL_0063
	HCCLM3	Adult hepatocellular carcinoma	Homo sapiens	CVCL_6832
In-vivo Model	For lung metastasis model, 1 × 106 HCC cells suspended in 100 ul serum free DMEM were injected via the tail vein of nude mice.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[37]
Response Summary	WTAP-guided m6A modification contributes to the progression of Hepatocellular carcinoma cells via the HuR-Protein C-ets-1 (ETS1)-p21/p27 axis.
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulator	Wilms tumor 1-associating protein (WTAP)		WRITER	Regulator Info
Target Regulation	Down regulation
Pathway Response	Cell cycle			hsa04110
Cell Process	Cell proliferation and tumor growth
	Cell apoptosis
	Arrest cell cycle at G2/M phase
In-vitro Model	HCCLM3	Adult hepatocellular carcinoma	Homo sapiens	CVCL_6832
	Hep 3B2.1-7	Childhood hepatocellular carcinoma	Homo sapiens	CVCL_0326
	Huh-7	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0336
	MHCC97-H	Adult hepatocellular carcinoma	Homo sapiens	CVCL_4972
	PLC/PRF/5	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0485
	QSG-7701	Endocervical adenocarcinoma	Homo sapiens	CVCL_6944
	SMMC-7721	Endocervical adenocarcinoma	Homo sapiens	CVCL_0534
In-vivo Model	3 × 106 treated HCC cells resuspended in 100 uL PBS were subcutaneously injected to the left flank of the mice, which were randomly divided into several groups. Tumor sizes were measured every 3 to 5 days.

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[38]
Response Summary	ZC3H13 overexpression sensitized to cisplatin and weakened metabolism reprogramming of HCC cells, ZC3H13-induced m6A modified patterns substantially abolished Pyruvate kinase PKM (PKM2/PKM) mRNA stability.
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Responsed Drug	Cisplatin		Approved	Drug Info
Target Regulator	Zinc finger CCCH domain-containing protein 13 (ZC3H13)		WRITER	Regulator Info
Target Regulation	Down regulation
Pathway Response	Central carbon metabolism in cancer			hsa05230
	Glycolysis / Gluconeogenesis			hsa00010
Cell Process	Glycolysis
In-vitro Model	SMMC-7721	Endocervical adenocarcinoma	Homo sapiens	CVCL_0534
	Huh-7	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0336
	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
	Hep 3B2.1-7	Childhood hepatocellular carcinoma	Homo sapiens	CVCL_0326
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[39]
Response Summary	the overexpression of demethylase FTO in the HCC tissue and cells. FTO could regulate the demethylation of Pyruvate kinase PKM (PKM2/PKM) in the hepatocellular carcinoma.
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulator	Fat mass and obesity-associated protein (FTO)		ERASER	Regulator Info
Target Regulation	Down regulation
Pathway Response	Central carbon metabolism in cancer			hsa05230
Cell Process	Glucose metabolism
In-vitro Model	Hep 3B2.1-7	Childhood hepatocellular carcinoma	Homo sapiens	CVCL_0326
	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
	Huh-7	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0336
	L-02	Endocervical adenocarcinoma	Homo sapiens	CVCL_6926
	SMMC-7721	Endocervical adenocarcinoma	Homo sapiens	CVCL_0534
In-vivo Model	The transfected cells (2×106) were directly subcutaneously injected in to flank of mice. The width and length were measured every six days. After three weeks, the mice were killed and the necropsies were weighted.

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[17]
Response Summary	METTL14 was found to inhibit HCC cell migration, invasion, and EMT through modulating EGFR/PI3K/RAC-alpha serine/threonine-protein kinase (AKT1) signaling pathway in an m6A-dependent manner.
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulator	Methyltransferase-like 14 (METTL14)		WRITER	Regulator Info
Target Regulation	Down regulation
Pathway Response	PI3K-Akt signaling pathway			hsa04151
Cell Process	Epithelial-mesenchymal transition
In-vitro Model	YY-8103	Adult hepatocellular carcinoma	Homo sapiens	CVCL_WY40
	SMMC-7721	Endocervical adenocarcinoma	Homo sapiens	CVCL_0534
	HCCLM3	Adult hepatocellular carcinoma	Homo sapiens	CVCL_6832
	L-02	Endocervical adenocarcinoma	Homo sapiens	CVCL_6926
	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
	Hep 3B2.1-7	Childhood hepatocellular carcinoma	Homo sapiens	CVCL_0326
In-vivo Model	For the lung metastasis model, stably transfected HepG2 cells (1 × 106/0.1 mL DMEM) were injected into each nude mouse through the tail vein. Five weeks later, mice were euthanized, and the lung tissues were collected.
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[40]
Response Summary	YTHDF1 contributes to the progression of HCC by activating PI3K/RAC-alpha serine/threonine-protein kinase (AKT1)/mTOR signaling pathway and inducing EMT.
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulator	YTH domain-containing family protein 1 (YTHDF1)		READER	Regulator Info
Target Regulation	Down regulation
Pathway Response	PI3K-Akt signaling pathway			hsa04151
	mTOR signaling pathway			hsa04150
Cell Process	Epithelial-mesenchymal transition
	Cell migration
	Cell invasion
	Cell proliferation
In-vitro Model	SNU-398	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0077
	SK-HEP-1	Liver and intrahepatic bile duct epithelial neoplasm	Homo sapiens	CVCL_0525
	PLC/PRF/5	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0485
	L-02	Endocervical adenocarcinoma	Homo sapiens	CVCL_6926
	Huh-7	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0336
	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
	Hep 3B2.1-7	Childhood hepatocellular carcinoma	Homo sapiens	CVCL_0326
	HEK293T	Normal	Homo sapiens	CVCL_0063
	HCCLM3	Adult hepatocellular carcinoma	Homo sapiens	CVCL_6832
In-vivo Model	Ten four-week-old BALB/c male nude mice (GemPharmatech, Jiangsu, China) were subcutaneously injected with control Huh7 cells 2 × 106 (left-back) and stable knockdown of YTHDF1 Huh7 cells 2 × 106 (right-back). These cells were respectively premixed with 50 ul Matrigel (Corning, 354,234) in 100 ul PBS.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[41]
Response Summary	AMD1 could stabilize the interaction of Ras GTPase-activating-like protein IQGAP1 (IQGAP1) with FTO, which then promotes FTO expression and increases HCC stemness.
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulator	Fat mass and obesity-associated protein (FTO)		ERASER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Ubiquitin mediated proteolysis			hsa04120
Cell Process	Proteasome pathway degradation
In-vitro Model	MHCC97-H	Adult hepatocellular carcinoma	Homo sapiens	CVCL_4972
	HCCLM3	Adult hepatocellular carcinoma	Homo sapiens	CVCL_6832
In-vivo Model	For subcutaneous xenotransplanted tumor models, cells were injected subcutaneously (5 × 106 for MHCC97H or 1×106 for PLC cells per mouse).

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[40]
Response Summary	YTHDF1 contributes to the progression of HCC by activating PI3K/AKT/Serine/threonine-protein kinase mTOR (MTOR) signaling pathway and inducing EMT.
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulator	YTH domain-containing family protein 1 (YTHDF1)		READER	Regulator Info
Target Regulation	Down regulation
Pathway Response	PI3K-Akt signaling pathway			hsa04151), mTOR signaling pathway
Cell Process	Epithelial-mesenchymal transition
	Cell migration
	Cell invasion
	Cell proliferation
In-vitro Model	SNU-398	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0077
	SK-HEP-1	Liver and intrahepatic bile duct epithelial neoplasm	Homo sapiens	CVCL_0525
	PLC/PRF/5	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0485
	L-02	Endocervical adenocarcinoma	Homo sapiens	CVCL_6926
	Huh-7	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0336
	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
	Hep 3B2.1-7	Childhood hepatocellular carcinoma	Homo sapiens	CVCL_0326
	HEK293T	Normal	Homo sapiens	CVCL_0063
	HCCLM3	Adult hepatocellular carcinoma	Homo sapiens	CVCL_6832
In-vivo Model	Ten four-week-old BALB/c male nude mice (GemPharmatech, Jiangsu, China) were subcutaneously injected with control Huh7 cells 2 × 106 (left-back) and stable knockdown of YTHDF1 Huh7 cells 2 × 106 (right-back). These cells were respectively premixed with 50 ul Matrigel (Corning, 354,234) in 100 ul PBS.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[2]
Response Summary	WTAP/Serine/threonine-protein kinase STK11 (STK11/LKB1)/AMPK axis in hepatocellular carcinoma cells acted as a key regulator, linking m6A with autophagy. WTAP-mediated m6A modification plays an important role in the regulation of autophagy in hepatocellular carcinoma cells, which provides a promising target for the treatment of hepatocellular carcinoma.
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulator	Wilms tumor 1-associating protein (WTAP)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	AMPK signaling pathway			hsa04152
	Autophagy			hsa04140
Cell Process	Cell autophagy
In-vitro Model	BEL-7402	Endocervical adenocarcinoma	Homo sapiens	CVCL_5492
	BEL-7404	Endocervical adenocarcinoma	Homo sapiens	CVCL_6568
	HEK293T	Normal	Homo sapiens	CVCL_0063
	L-02	Endocervical adenocarcinoma	Homo sapiens	CVCL_6926
	SMMC-7721	Endocervical adenocarcinoma	Homo sapiens	CVCL_0534

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[42]
Response Summary	YTHDF2 expression was associated positively with Splicing factor 3A subunit 3 (SF3A3) expression, which implied that they cooperate in LIHC progression.
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulator	YTH domain-containing family protein 2 (YTHDF2)		READER	Regulator Info
Target Regulation	Up regulation
Cell Process	Immunity

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[43]
Response Summary	METTL3 is frequently up-regulated in human HCC and contributes to HCC progression. METTL3 represses Suppressor of cytokine signaling 2 (SOCS2) expression in HCC through an m6A-YTHDF2-dependent mechanism.
Responsed Disease	Liver cancer [ICD-11: 2C12]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Down regulation
Cell Process	Cells proliferation
	Cells migration
	Cells invasion
	RNA degradation (hsa03018)
In-vitro Model	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
	Huh-7	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0336
	MHCC97-L	Adult hepatocellular carcinoma	Homo sapiens	CVCL_4973
In-vivo Model	For the subcutaneous implantation model, 2 × 106 METTL3 stable knockdown Huh-7 cells or METTL3 overexpression MHCC97L cells were injected subcutaneously into BABL/cAnN-nude mice. For orthotopic implantation, wild-type and METTL3 knockout Huh-7 cells were luciferase labelled, and 2 × 106 cells were then injected orthotopically into the left liver lobe of nude mice.
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[43]
Response Summary	METTL3 is frequently up-regulated in human HCC and contributes to HCC progression. METTL3 represses Suppressor of cytokine signaling 2 (SOCS2) expression in HCC through an m6A-YTHDF2-dependent mechanism.
Responsed Disease	Liver cancer [ICD-11: 2C12]
Target Regulator	YTH domain-containing family protein 2 (YTHDF2)		READER	Regulator Info
Target Regulation	Down regulation
Cell Process	Cells proliferation
	Cells migration
	Cells invasion
	RNA degradation (hsa03018)
In-vitro Model	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
	Huh-7	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0336
	MHCC97-L	Adult hepatocellular carcinoma	Homo sapiens	CVCL_4973
In-vivo Model	For the subcutaneous implantation model, 2 × 106 METTL3 stable knockdown Huh-7 cells or METTL3 overexpression MHCC97L cells were injected subcutaneously into BABL/cAnN-nude mice. For orthotopic implantation, wild-type and METTL3 knockout Huh-7 cells were luciferase labelled, and 2 × 106 cells were then injected orthotopically into the left liver lobe of nude mice.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[18]
Response Summary	In contrast to the mRNA-decay-promoting function of YTH domain-containing family protein 2, IGF2BPs promote the stability and storage of their target mRNAs (for example, MYC) in an m6A-dependent manner under normal and stress conditions and therefore affect gene expression output. Four representative high confidence targets, including MYC, FSCN1, Thymidine kinase, cytosolic (TK1), and MARCKSL1, exhibit strong binding with IGF2BPs around their m6A motifs in control cells. Knocking down of each individual IGF2BPs in Hela (cervical cancer) and HepG2 (liver cancer) cells significantly repressed MYC expression.
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulator	Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1)		READER	Regulator Info
Cell Process	RNA decay
In-vitro Model	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
	HEK293T	Normal	Homo sapiens	CVCL_0063
	HeLa	Endocervical adenocarcinoma	Homo sapiens	CVCL_0030
	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[44]
Response Summary	KIAA1429 induced m6A methylation on the 3' UTR of Trans-acting T-cell-specific transcription factor GATA-3 (GATA3) pre-mRNA, leading to the separation of the RNA-binding protein HuR and the degradation of GATA3 pre-mRNA. KIAA1429 was considerably upregulated in Hepatocellular carcinoma tissues.
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulator	Protein virilizer homolog (VIRMA)		WRITER	Regulator Info
Target Regulation	Down regulation
Cell Process	Cell proliferation and metastasis
In-vitro Model	HCCLM3	Adult hepatocellular carcinoma	Homo sapiens	CVCL_6832
	HEK293T	Normal	Homo sapiens	CVCL_0063
	Hep 3B2.1-7	Childhood hepatocellular carcinoma	Homo sapiens	CVCL_0326
	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
	Huh-7	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0336
	SK-HEP-1	Liver and intrahepatic bile duct epithelial neoplasm	Homo sapiens	CVCL_0525
	SNU-182	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0090
	SNU-449	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0454

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[45]
Response Summary	m6A methylation plays a key role in VM formation in HCC. METTL3 and Transcriptional coactivator YAP1 (YAP1) could be potential therapeutic targets via impairing VM formation in anti-metastatic strategies.
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Hippo signaling pathway			hsa04390
Cell Process	Cell migration and invasion
In-vitro Model	Homo sapiens (SK-HEP-1-Luc (luciferase labeled) cells were obtained from OBIO (Shanghai, China).)
	MHCC97-H	Adult hepatocellular carcinoma	Homo sapiens	CVCL_4972
	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
In-vivo Model	1 × 107 SK-HEP-1-Luc-shControl or SK-HEP-1-Luc-shMETTL3 stable cells were suspended in 300 uL of PBS and injected orthotopically into the left liver lobe of nude mice.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[46]
Response Summary	RNA decay assay showed that oncogene Transcriptional enhancer factor TEF-4 (TEAD2) mRNA stability was impaired by FTO. The overexpression of FTO suppressed tumor growth in vivo. In conclusion, our study demonstrated the critical roles of FTO in Intrahepatic cholangiocarcinoma.
Responsed Disease	Intrahepatic cholangiocarcinoma [ICD-11: 2C12.10]
Target Regulator	Fat mass and obesity-associated protein (FTO)		ERASER	Regulator Info
Target Regulation	Down regulation
Cell Process	Cell cycle
	Cell proliferation
In-vitro Model	HCCC-9810	Intrahepatic cholangiocarcinoma	Homo sapiens	CVCL_6908
	HIBEPIC (Human intrahepatic bile duct epithelial cells)
	HuCC-T1	Intrahepatic cholangiocarcinoma	Homo sapiens	CVCL_0324
	RBE	Intrahepatic cholangiocarcinoma	Homo sapiens	CVCL_4896
	TFK-1	Cholangiocarcinoma	Homo sapiens	CVCL_2214
In-vivo Model	1.5 × 106 TFK1 cells with or without FTO overexpression were injected subcutaneously into the left and right flanks of 6-week-old female athymic nude mice

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[47]
Response Summary	Overexpression of RBM15B promotes HCC cell proliferation and invasion and induces sorafenib resistance in HCC cells. RBM15B is transcriptionally activated by YY1 and regulates the stability of Translocating chain-associated membrane protein 2 (TRAM2) mRNA in an m6A-dependent manner.
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Responsed Drug	Sorafenib		Approved	Drug Info
Target Regulator	RNA-binding motif protein 15B (RBM15B)		WRITER	Regulator Info
Target Regulation	Up regulation
In-vitro Model	SK-HEP-1	Liver and intrahepatic bile duct epithelial neoplasm	Homo sapiens	CVCL_0525
	Huh-7	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0336
	L-02	Endocervical adenocarcinoma	Homo sapiens	CVCL_6926
	Hep-G2.215 (Hep-G2.215 were purchased from the Shanghai Cell Bank of the Chinese Academy of Sciences)
	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
	HCCLM3	Adult hepatocellular carcinoma	Homo sapiens	CVCL_6832
	7721 (Human hepatic malignant cell line)
In-vivo Model	HCC-LM3 cells transfected with sh-NC and sh-RBM15B-3 were injected into the axilla or tail vein of mice.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[36]
Response Summary	PA2G4 plays a pro-metastatic role by increasing Tyrosine-protein kinase Fyn (FYN) expression through binding with YTHDF2 in HCC. PA2G4 becomes a reliable prognostic marker or therapeutic target for HCC patients.
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulator	YTH domain-containing family protein 2 (YTHDF2)		READER	Regulator Info
Target Regulation	Up regulation
Cell Process	Cell metastatic
In-vitro Model	PLC/PRF/5	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0485
	MHCC97-H	Adult hepatocellular carcinoma	Homo sapiens	CVCL_4972
	Huh-7	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0336
	HLF	Adult hepatocellular carcinoma	Homo sapiens	CVCL_2947
	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
	Hep 3B2.1-7	Childhood hepatocellular carcinoma	Homo sapiens	CVCL_0326
	HEK293T	Normal	Homo sapiens	CVCL_0063
	HCCLM3	Adult hepatocellular carcinoma	Homo sapiens	CVCL_6832
In-vivo Model	For lung metastasis model, 1 × 106 HCC cells suspended in 100 ul serum free DMEM were injected via the tail vein of nude mice.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[33]
Response Summary	Methyltransferase-like 14 (Mettl14)-induced m6A modification participated in the regulation of Ubiquitin carboxyl-terminal hydrolase 48 (USP48) in hepatocellular carcinoma by maintaining USP48 mRNA stability. This work uncovers the tumor-suppressive function of the Mettl14-USP48-SIRT6 axis via modulation of glycolysis, providing new insights into the critical roles of metabolic activities in HCC and identifying an attractive target for future treatment studies.
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulator	Methyltransferase-like 14 (METTL14)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Ubiquitin mediated proteolysis			hsa04120
	Glycolysis / Gluconeogenesis			hsa00010
Cell Process	Ubiquitination degradation
	Glycolysis
In-vitro Model	BEL-7404	Endocervical adenocarcinoma	Homo sapiens	CVCL_6568
	Huh-7	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0336
	SK-HEP-1	Liver and intrahepatic bile duct epithelial neoplasm	Homo sapiens	CVCL_0525
	SK-HEP-1	Liver and intrahepatic bile duct epithelial neoplasm	Homo sapiens	CVCL_0525
In-vivo Model	Hepatocyte-specific knockout USP48 was obtained by crossing Alb-Cre mice with USP48flox/flox mice.

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[48]
Response Summary	METTL3 regulates the expression of Ubiquitin carboxyl-terminal hydrolase 7 (USP7) through m6A methylation and facilitate the invasion, migration and proliferation of HCC cells. Besides, the elevated METTL3 expression was related to worse overall survival.
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Cell Process	Cell invasion
	Cell migration
	Cell proliferation
In-vitro Model	MHCC97-L	Adult hepatocellular carcinoma	Homo sapiens	CVCL_4973
	L-02	Endocervical adenocarcinoma	Homo sapiens	CVCL_6926
	Huh-7	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0336
	Hep 3B2.1-7	Childhood hepatocellular carcinoma	Homo sapiens	CVCL_0326
	HCCLM3	Adult hepatocellular carcinoma	Homo sapiens	CVCL_6832
In-vivo Model	Male nu/nu mice between 4 and 6 weeks of age received subcutaneous injections of equivalent Hep3B cells expressing either LV-shMETTL3 or LV-USP7 within 30 min of harvesting on the right and left flanks. The tumor was weighed after approximately 4 weeks, and the volume was measured every 5 days.
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[49]
Response Summary	Ubiquitin carboxyl-terminal hydrolase 7 (USP7) was upregulated in HCC and associated with METTL3 level positively. USP7 silencing decreased proliferation, migration, and invasion rates of HCC cells. METTL3 promotes HCC to proliferate, migrate, and invade by regulating m6A methylation of USP7.
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Cell Process	Cell proliferate
	Cell migrate
	Cell invade
In-vitro Model	MHCC97-L	Adult hepatocellular carcinoma	Homo sapiens	CVCL_4973
	L-02	Endocervical adenocarcinoma	Homo sapiens	CVCL_6926
	Huh-7	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0336
	Hep 3B2.1-7	Childhood hepatocellular carcinoma	Homo sapiens	CVCL_0326
	HCCLM3	Adult hepatocellular carcinoma	Homo sapiens	CVCL_6832

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[3]
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]
Responsed Drug	Sorafenib		Approved	Drug Info
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	FoxO signaling pathway			hsa04068
	Autophagy			hsa04140
Cell Process	Cell autophagy
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[3]
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]
Responsed Drug	Sorafenib		Approved	Drug Info
Target Regulator	YTH domain-containing family protein 1 (YTHDF1)		READER	Regulator Info
Target Regulation	Up regulation
Pathway Response	FoxO signaling pathway			hsa04068
	Autophagy			hsa04140
Cell Process	Cell autophagy

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[3]
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, ATG7, Ubiquitin-like protein ATG12 (ATG12), and ATG16L1.
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Responsed Drug	Sorafenib		Approved	Drug Info
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	FoxO signaling pathway			hsa04068
	Autophagy			hsa04140
Cell Process	Cell autophagy
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[3]
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, ATG7, Ubiquitin-like protein ATG12 (ATG12), and ATG16L1.
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Responsed Drug	Sorafenib		Approved	Drug Info
Target Regulator	YTH domain-containing family protein 1 (YTHDF1)		READER	Regulator Info
Target Regulation	Up regulation
Pathway Response	FoxO signaling pathway			hsa04068
	Autophagy			hsa04140
Cell Process	Cell autophagy

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[3]
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 Ubiquitin-like-conjugating enzyme ATG3 (ATG3), ATG5, ATG7, ATG12, and ATG16L1.
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Responsed Drug	Sorafenib		Approved	Drug Info
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	FoxO signaling pathway			hsa04068
	Autophagy			hsa04140
Cell Process	Cell autophagy
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[3]
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 Ubiquitin-like-conjugating enzyme ATG3 (ATG3), ATG5, ATG7, ATG12, and ATG16L1.
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Responsed Drug	Sorafenib		Approved	Drug Info
Target Regulator	YTH domain-containing family protein 1 (YTHDF1)		READER	Regulator Info
Target Regulation	Up regulation
Pathway Response	FoxO signaling pathway			hsa04068
	Autophagy			hsa04140
Cell Process	Cell autophagy

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[50]
Response Summary	RBM15-mediated m6A modification contributed to a post-transcriptional activation of Yes tyrosine kinase (YES/YES1) in an IGF2BP1-dependent manner. RBM15-mediated m6A modification facilitate the progression of HCC via the IGF2BP1-YES1-MAPK axis.
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulator	RNA-binding motif protein 15 (RBM15)		WRITER	Regulator Info
Pathway Response	MAPK signaling pathway			hsa04010
In-vitro Model	HCC-LM3 (HCC-LM3 were obtained from Guangzhou Cellcook Biotech Co., Ltd.)
	MHCC97-H	Adult hepatocellular carcinoma	Homo sapiens	CVCL_4972
	B76.1/Huh7	Adult hepatocellular carcinoma	Homo sapiens	CVCL_U443
In-vivo Model	5 × 106 Huh7 and HCC-LM3 cells resuspended in 100ul PBS were subcutaneously injected to the left flank of the mice (randomly selected, five mice per group for Huh7 cells in the first time and ten mice per group for HCC-LM3 cells in the second time. No blinding was performed).

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[51]
Response Summary	circ_KIAA1429 could accelerate HCC advancement, maintained the expression of Zeb1 through the mechanism of m6A-YTHDF3-Zinc finger E-box-binding homeobox 1 (ZEB1) in hepatocellular carcinoma.
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulator	YTH domain-containing family protein 3 (YTHDF3)		READER	Regulator Info
Target Regulation	Up regulation
Pathway Response	RNA degradation			hsa03018
Cell Process	RNA stability
In-vitro Model	BEL-7402	Endocervical adenocarcinoma	Homo sapiens	CVCL_5492
	BEL-7404	Endocervical adenocarcinoma	Homo sapiens	CVCL_6568
	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
	Huh-7	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0336
	L-02	Endocervical adenocarcinoma	Homo sapiens	CVCL_6926
	SMMC-7721	Endocervical adenocarcinoma	Homo sapiens	CVCL_0534
In-vivo Model	1 × 107 Bel-7404 cells in 200 uL PBS were injected into the right flank of nude mice.

In total 3 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[52]
Response Summary	The upregulation of METTL3 and YTHDF1 act as adverse prognosis factors for overall survival (OS) rate of liver cancer patients. m6A-sequencing and functional studies confirm that Zinc finger protein SNAI1 (SNAI1), a key transcription factor of EMT, is involved in m6A-regulated EMT.
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Cell Process	Epithelial-mesenchymal transition
	cell migration
	invasion
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	HeLa	Endocervical adenocarcinoma	Homo sapiens	CVCL_0030
	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
	Huh-7	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0336
In-vivo Model	All animal experiments complied with Zhongshan School of Medicine Policy on Care and Use of Laboratory Animals. For subcutaneous transplanted model, sh-control and sh-METTL3 Huh7 cells (5 × 106 per mouse, n = 5 for each group) were diluted in 200 uL of PBS + 200 uL Matrigel (BD Biosciences) and subcutaneously injected into immunodeficient female mice to investigate tumor growth.
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[52]
Response Summary	The upregulation of METTL3 and YTHDF1 act as adverse prognosis factors for overall survival (OS) rate of liver cancer patients. m6A-sequencing and functional studies confirm that Zinc finger protein SNAI1 (SNAI1), a key transcription factor of EMT, is involved in m6A-regulated EMT.
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulator	YTH domain-containing family protein 1 (YTHDF1)		READER	Regulator Info
Target Regulation	Up regulation
Cell Process	Epithelial-mesenchymal transition
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	HeLa	Endocervical adenocarcinoma	Homo sapiens	CVCL_0030
	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
	Huh-7	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0336
In-vivo Model	All animal experiments complied with Zhongshan School of Medicine Policy on Care and Use of Laboratory Animals. For subcutaneous transplanted model, sh-control and sh-METTL3 Huh7 cells (5 × 106 per mouse, n = 5 for each group) were diluted in 200 uL of PBS + 200 uL Matrigel (BD Biosciences) and subcutaneously injected into immunodeficient female mice to investigate tumor growth.
Experiment 3 Reporting the m6A-centered Disease Response by This Target Gene				[53]
Response Summary	SUMOylation of Mettl3 was found to regulate hepatocellular carcinoma progression via controlling Zinc finger protein SNAI1 (SNAI1) mRNA homeostasis in an m6A methyltransferase activity-dependent manner.
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Nucleotide excision repair			hsa03420
Cell Process	RNA stability
In-vitro Model	Hep 3B2.1-7	Childhood hepatocellular carcinoma	Homo sapiens	CVCL_0326
	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
	MHCC97-H	Adult hepatocellular carcinoma	Homo sapiens	CVCL_4972
	SMMC-7721	Endocervical adenocarcinoma	Homo sapiens	CVCL_0534
In-vivo Model	1×106/mouse cells were suspended in 50 uL of serum-free DMEM and subcutaneously injected into the flank of each mouse. Tumor diameters and volume (length × width2 × 0.5236) were calculated every other day using calipers.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[54]
Response Summary	LncRNA activating regulator of DKK1 (LNCAROD) induces PKM2 upregulation via simultaneously enhancing SRSF3-mediated PKM switching to PKM2 and sponging miR-145-5p to increase PKM2 level, eventually increasing hepatocellular carcinoma cell aerobic glycolysis to participate in tumor malignancy and chemoresistance, especially under hypoxic microenvironment.
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Pathway Response	Glycolysis / Gluconeogenesis			hsa00010
Cell Process	Aerobic glycolysis
In-vitro Model	HCCLM3	Adult hepatocellular carcinoma	Homo sapiens	CVCL_6832
	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
	Huh-7	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0336
	SMMC-7721	Endocervical adenocarcinoma	Homo sapiens	CVCL_0534
	SNU-182	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0090
	SNU-449	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0454
	THLE-2	Normal	Homo sapiens	CVCL_3803
In-vivo Model	HCC-LM3 cells with silenced LNCAROD or the negative control were subcutaneously injected into the flank region of the mice at 2 × 106 cells.

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[55]
Response Summary	Long intergenic non-protein coding RNA 1273 (LINC01273) was modified with m6A, METTL3 increased LINC01273 m6A modification, followed by LINC01273 decay in the presence of YTHDF2, a m6A 'reader'. And LINC01273 plays a key role in sorafenib resistant HCC cells.
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Responsed Drug	Sorafenib		Approved	Drug Info
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Down regulation
In-vitro Model	SMMC-7721	Endocervical adenocarcinoma	Homo sapiens	CVCL_0534
	Huh-7	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0336
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[55]
Response Summary	Long intergenic non-protein coding RNA 1273 (LINC01273) was modified with m6A, METTL3 increased LINC01273 m6A modification, followed by LINC01273 decay in the presence of YTHDF2, a m6A 'reader'. And LINC01273 plays a key role in sorafenib resistant HCC cells.
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Responsed Drug	Sorafenib		Approved	Drug Info
Target Regulator	YTH domain-containing family protein 2 (YTHDF2)		READER	Regulator Info
Target Regulation	Down regulation
In-vitro Model	SMMC-7721	Endocervical adenocarcinoma	Homo sapiens	CVCL_0534
	Huh-7	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0336

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[56]
Response Summary	Long intergenic non-protein coding RNA 958 (LINC00958) sponged miR-3619-5p to upregulate hepatoma-derived growth factor (HDGF) expression, thereby facilitating Hepatocellular carcinoma lipogenesis and progression. METTL3-mediated N6-methyladenosine modification led to LINC00958 upregulation through stabilizing its RNA transcript.
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	mRNA surveillance pathway			hsa03015
Cell Process	RNA stability
	Lipogenesis
In-vitro Model	FOCUS	Adult hepatocellular carcinoma	Homo sapiens	CVCL_7955
	HCCLM3	Adult hepatocellular carcinoma	Homo sapiens	CVCL_6832
	HEp-2	Endocervical adenocarcinoma	Homo sapiens	CVCL_1906
	Hep 3B2.1-7	Childhood hepatocellular carcinoma	Homo sapiens	CVCL_0326
	Huh-7	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0336
	MHCC97-H	Adult hepatocellular carcinoma	Homo sapiens	CVCL_4972
	QSG-7701	Endocervical adenocarcinoma	Homo sapiens	CVCL_6944

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[57]
Response Summary	Maternally expressed 3 (MEG3) regulates the expression of BTG2 through miR-544b, thus affecting the malignant behavior of hepatocellular carcinoma. METTL3 regulates the m6A modification of MEG3 and its expression.
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Down regulation
Cell Process	Cell proliferation
	Cell migration
	Cell invasion
In-vitro Model	Hep 3B2.1-7	Childhood hepatocellular carcinoma	Homo sapiens	CVCL_0326
	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
	Huh-7	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0336
	MHCC97-H	Adult hepatocellular carcinoma	Homo sapiens	CVCL_4972
	THLE-3	Normal	Homo sapiens	CVCL_3804

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[58]
Response Summary	Identified the lncRNA NIFK antisense RNA 1 (NIFK-AS1) as being highly expressed in hepatocellular carcinoma tissues and cells, promotes disease progression and sorafenib resistance, and showed this up-regulation resulted from METTL3-dependent m6A methylation.
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Responsed Drug	Sorafenib		Approved	Drug Info
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
In-vitro Model	Hep 3B2.1-7	Childhood hepatocellular carcinoma	Homo sapiens	CVCL_0326
	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
	Huh-7	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0336
	MHCC97-H	Adult hepatocellular carcinoma	Homo sapiens	CVCL_4972
	THLE-3	Normal	Homo sapiens	CVCL_3804
In-vivo Model	For the PDX model, fresh patient HCC tissues were cut into fragments with a volume of 3 × 3 mm3 and then implanted subcutaneously into the flanks of nude mice. The mice were given sorafenib (30 mg/kg) or vehicle orally twice a week for 24 days. This procedure was approved by the Ethics Committee of Jinling Hospital.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[59]
Response Summary	m6A methylation triggers the upregulation of Non-protein coding RNA 106 (LINC00106), which promotes the stemness and metastasis properties in HCC cells by sponging let7f, thereby resulting in periostin activation. The findings indicate the potential of LINC00106 as a diagnostic marker and therapeutic target for HCC.
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Pathway Response	PI3K-Akt signaling pathway			hsa04151
Cell Process	Stemness property
	Metastasis
In-vitro Model	MHCC97-H	Adult hepatocellular carcinoma	Homo sapiens	CVCL_4972
	SNU-449	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0454
	B76.1/Huh7	Adult hepatocellular carcinoma	Homo sapiens	CVCL_U443
	Hep 3B2.1-7	Childhood hepatocellular carcinoma	Homo sapiens	CVCL_0326
	BEL-7405	Adult hepatocellular carcinoma	Homo sapiens	CVCL_6569
	HCC-LM3 (HCC-LM3 were obtained from Guangzhou Cellcook Biotech Co., Ltd.)
	THLE-2	Normal	Homo sapiens	CVCL_3803

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[60]
Response Summary	ALKBH5 could up-regulate Nuclear paraspeckle assembly transcript 1 (NEAT1) expression by inhibiting m6A enrichment. ALKBH5-induced NEAT1 promoted cell proliferation and migration of HCC by sponging miR-214 in vitro, which provided a potential therapeutic target for HCC.
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulator	RNA demethylase ALKBH5 (ALKBH5)		ERASER	Regulator Info
Target Regulation	Up regulation
Cell Process	Cell proliferation and migration
	Cell apoptosis
In-vitro Model	SMMC-7721	Endocervical adenocarcinoma	Homo sapiens	CVCL_0534
	L-02	Endocervical adenocarcinoma	Homo sapiens	CVCL_6926
	Huh-7	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0336

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[61]
Response Summary	The study demonstrated that the 9 m6A-related lncRNA signature serves as a novel predictor in the prognosis of hepatocellular Carcinoma and optimize (ICIs) therapy. Small nucleolar RNA host gene 4 (SNHG4) plays an oncogenic role in hepatocellular Carcinoma.
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
In-vitro Model	Huh-7	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0336
	LM3	Malignant neoplasms	Mus musculus	CVCL_D269
	PLC/PRF/5	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0485

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[62]
Response Summary	circ-ARL3 is a critical regulator in HBV-related HCC, targeting the axis of circ-ARL3/microRNA 1305 (MIR1305) can be a promising treatment for HBV+ HCC patients. HBx protein upregulated N6 -methyladenosine (m6A) methyltransferases METTL3 expression, increasing the m6A modification of circ-ARL3; then, m6A reader YTHDC1 bound to m6 A-modified of circ-ARL3 and favored its reverse splicing and biogenesis. Furthermore, circ-ARL3 was able to sponge miR-1305, antagonizing the inhibitory effects of miR-1305 on a cohort of target oncogenes, thereby promoting HBV+ HCC progression.
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Cell Process	Reverse splicing and biogenesis
In-vitro Model	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
In-vivo Model	Mice were randomly divided into three groups, and subcutaneously injected with control, circ-ARL3-silenced and circ-ARL3&miR-1305-silenced HepG2.2.15 cells.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[63]
Response Summary	microRNA 186 (MIR186)/METTL3 axis contributed to the progression of Hepatoblastoma via the Wnt/beta-catenin signalling pathway.
Responsed Disease	Hepatoblastoma [ICD-11: 2C12.01]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Down regulation
Pathway Response	Wnt signaling pathway			hsa04310
Cell Process	Cell aggressive
In-vitro Model	HCCLM9	Adult hepatocellular carcinoma	Homo sapiens	CVCL_A5CU
	HEK293	Normal	Homo sapiens	CVCL_0045
	Hepa 1-6	Hepatocellular carcinoma of the mouse	Mus musculus	CVCL_0327
	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
	HuH-6	Hepatoblastoma	Homo sapiens	CVCL_4381
In-vivo Model	Cells transfected with miR-186 overexpression lentivirus (Lenti-miR-186), miR-186 inhibitor (Lenti-anti-miR-186), Lenti-miR-186 & METTL3 overexpression plasmid (Lenti-METTL3), Lenti-anti-miR-186 & METTL3 shRNA (sh-METTL3) or empty lentivirus control (Lenti-NC) were subcutaneously injected into the lower flank of nude mice.

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[24]
Response Summary	In hepatocellular carcinoma, METTL3 could direct the formation of circHPS5, and specific m6A controlled the accumulation of circHPS5. YTHDC1 facilitated the cytoplasmic output of circHPS5 under m6A modification. CircHPS5 can act as a microRNA 370 (MIR370) sponge to regulate the expression of HMGA2 and further accelerate hepatocellular carcinoma cell tumorigenesis.
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Pathway Response	Transcriptional misregulation in cancer			hsa05202
Cell Process	Epithelial-mesenchymal transition
	Cell autophagy
In-vitro Model	Hep 3B2.1-7	Childhood hepatocellular carcinoma	Homo sapiens	CVCL_0326
	L-02	Endocervical adenocarcinoma	Homo sapiens	CVCL_6926
In-vivo Model	To create the xenograft neoplasm system, 40 male BALB/c nude mice aged 5 weeks were randomly separated into sh-NC, sh-circHPS5, sh-circHPS5+CTRL, and sh-circHPS5+SAH groups (n = 5 for each group). HCC cells were subcutaneously injected into the axilla of the nude mice.
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[24]
Response Summary	In hepatocellular carcinoma, METTL3 could direct the formation of circHPS5, and specific m6A controlled the accumulation of circHPS5. YTHDC1 facilitated the cytoplasmic output of circHPS5 under m6A modification. CircHPS5 can act as a microRNA 370 (MIR370) sponge to regulate the expression of HMGA2 and further accelerate hepatocellular carcinoma cell tumorigenesis.
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulator	YTH domain-containing protein 1 (YTHDC1)		READER	Regulator Info
Pathway Response	Transcriptional misregulation in cancer			hsa05202
Cell Process	Epithelial-mesenchymal transition
	Cell autophagy
In-vitro Model	Hep 3B2.1-7	Childhood hepatocellular carcinoma	Homo sapiens	CVCL_0326
	L-02	Endocervical adenocarcinoma	Homo sapiens	CVCL_6926
In-vivo Model	To create the xenograft neoplasm system, 40 male BALB/c nude mice aged 5 weeks were randomly separated into sh-NC, sh-circHPS5, sh-circHPS5+CTRL, and sh-circHPS5+SAH groups (n = 5 for each group). HCC cells were subcutaneously injected into the axilla of the nude mice.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[64]
Response Summary	NKILA physically interacted with and suppressed hsa-miR-582-3p, which was regulated by METTL3-mediated N6 -methyladenosine (m6A) modification. YAP1 was a target of NKILA via miR-582-3p and NKILA functioned partially via YAP1 in CCA.
Responsed Disease	Intrahepatic cholangiocarcinoma [ICD-11: 2C12.10]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
In-vitro Model	TFK-1	Cholangiocarcinoma	Homo sapiens	CVCL_2214
	RBE	Intrahepatic cholangiocarcinoma	Homo sapiens	CVCL_4896
	HuH-28	Cholangiocarcinoma	Homo sapiens	CVCL_2955
	HuCC-T1	Intrahepatic cholangiocarcinoma	Homo sapiens	CVCL_0324
	HIBEpic (Human intrahepatic bile duct epithelial cells)
	CC-LP-1	Intrahepatic cholangiocarcinoma	Homo sapiens	CVCL_0205
In-vivo Model	To detect the effect of NKILA on CAA growth, 5 × 106 control and NKILA-depleted HuCCT1 cells (n = 4 per group) were subcutaneously injected into male BALB/c nude mice (4-6 weeks old).

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[65]
Response Summary	METTL3 up-regulated the expression of hsa-miR-589-5p and promoted the maturation of miR-589-5p. Overexpressed miR-589-5p and METTL3 promoted the viability, migration and invasion of liver cancer cells.
Responsed Disease	Liver cancer [ICD-11: 2C12]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Adherens junction			hsa04520
Cell Process	Cell migration
	Cell invasion
In-vitro Model	THLE-2	Normal	Homo sapiens	CVCL_3803
	SNU-423	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0366
	SNU-387	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0250
	SNU-182	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0090
	SK-HEP-1	Liver and intrahepatic bile duct epithelial neoplasm	Homo sapiens	CVCL_0525
	PLC/PRF/5	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0485
	Hep 3B2.1-7	Childhood hepatocellular carcinoma	Homo sapiens	CVCL_0326
	HEK293T	Normal	Homo sapiens	CVCL_0063
In-vivo Model	The mice were fed in an SPF environment (cycle of 12-h light and 12-h dark) with a free diet. All the mice were adaptively fed for 5 days before experiments and randomly divided into the following four groups: the siNC+MC group (n = 10), the METTL3 siRNA1+MC group (n = 10), siNC+M group (n = 10) and the METTL3 siRNA1+M group (n = 10). Then, the right forelimb of mice in the siNC+MC group was subcutaneously injected with 100 uL PBS containing 1 × 106 SK-Hep1 cells co-transfected with siNC and MC; the right forelimb of mice in the METTL3 siRNA1+MC group was subcutaneously injected with 100 uL PBS containing 1 × 106 SK-Hep1 cells co-transfected with METTL3 siRNA1 and MC; the right forelimb of mice in the siNC+M group was subcutaneously injected with 100 uL PBS containing 1 × 106 SK-Hep1 cells co-transfected with siNC and M; the right forelimb of mice in the METTL3 siRNA1+M group was subcutaneously injected with 100 uL PBS containing 1 × 106 SK-Hep1 cells co-transfected with METTL3 siRNA1 and M.

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[24]
Response Summary	In hepatocellular carcinoma, METTL3 could direct the formation of hsa_circ_0021427 (circHPS5), and specific m6A controlled the accumulation of circHPS5. YTHDC1 facilitated the cytoplasmic output of circHPS5 under m6A modification. CircHPS5 can act as a miR-370 sponge to regulate the expression of HMGA2 and further accelerate hepatocellular carcinoma cell tumorigenesis.
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Transcriptional misregulation in cancer			hsa05202
Cell Process	Epithelial-mesenchymal transition
	Cell autophagy
In-vitro Model	Hep 3B2.1-7	Childhood hepatocellular carcinoma	Homo sapiens	CVCL_0326
	L-02	Endocervical adenocarcinoma	Homo sapiens	CVCL_6926
In-vivo Model	To create the xenograft neoplasm system, 40 male BALB/c nude mice aged 5 weeks were randomly separated into sh-NC, sh-circHPS5, sh-circHPS5+CTRL, and sh-circHPS5+SAH groups (n = 5 for each group). HCC cells were subcutaneously injected into the axilla of the nude mice.
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[24]
Response Summary	In hepatocellular carcinoma, METTL3 could direct the formation of circHPS5, and specific m6A controlled the accumulation of circHPS5. YTHDC1 facilitated the cytoplasmic output of hsa_circ_0021427 (circHPS5) under m6A modification. CircHPS5 can act as a miR-370 sponge to regulate the expression of HMGA2 and further accelerate hepatocellular carcinoma cell tumorigenesis.
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulator	YTH domain-containing protein 1 (YTHDC1)		READER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Transcriptional misregulation in cancer			hsa05202
Cell Process	Epithelial-mesenchymal transition
	Cell autophagy
In-vitro Model	Hep 3B2.1-7	Childhood hepatocellular carcinoma	Homo sapiens	CVCL_0326
	L-02	Endocervical adenocarcinoma	Homo sapiens	CVCL_6926
In-vivo Model	To create the xenograft neoplasm system, 40 male BALB/c nude mice aged 5 weeks were randomly separated into sh-NC, sh-circHPS5, sh-circHPS5+CTRL, and sh-circHPS5+SAH groups (n = 5 for each group). HCC cells were subcutaneously injected into the axilla of the nude mice.

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[66]
Response Summary	In hepatocellular carcinoma, hsa_circ_0058493 contained m6A methylation sites and that METTL3 mediated the degree of methylation modification of hsa_circ_0058493. YTHDC1 could bind to hsa_circ_0058493 and promote its intracellular localization from the nucleus to the cytoplasm.
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Hepatocellular carcinoma			hsa05225
Cell Process	Cell growth and metastasis
In-vitro Model	BEL-7404	Endocervical adenocarcinoma	Homo sapiens	CVCL_6568
	HCCLM3	Adult hepatocellular carcinoma	Homo sapiens	CVCL_6832
	L-02	Endocervical adenocarcinoma	Homo sapiens	CVCL_6926
	MHCC97-H	Adult hepatocellular carcinoma	Homo sapiens	CVCL_4972
	SK-HEP-1	Liver and intrahepatic bile duct epithelial neoplasm	Homo sapiens	CVCL_0525
	SMMC-7721	Endocervical adenocarcinoma	Homo sapiens	CVCL_0534
In-vivo Model	Groups of HCT116-Luc-shCtrl, HCT116-Luc-shLINC00460, and HCT116-Luc-shLINC00460 + HMGA1 cells (5 × 106) were injected subcutaneously into the flanks of mice correspondingly.
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[66]
Response Summary	In hepatocellular carcinoma, hsa_circ_0058493 contained m6A methylation sites and that METTL3 mediated the degree of methylation modification of hsa_circ_0058493. YTHDC1 could bind to hsa_circ_0058493 and promote its intracellular localization from the nucleus to the cytoplasm.
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulator	YTH domain-containing protein 1 (YTHDC1)		READER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Hepatocellular carcinoma			hsa05225
Cell Process	Cell growth and metastasis
In-vitro Model	BEL-7404	Endocervical adenocarcinoma	Homo sapiens	CVCL_6568
	HCCLM3	Adult hepatocellular carcinoma	Homo sapiens	CVCL_6832
	L-02	Endocervical adenocarcinoma	Homo sapiens	CVCL_6926
	MHCC97-H	Adult hepatocellular carcinoma	Homo sapiens	CVCL_4972
	SK-HEP-1	Liver and intrahepatic bile duct epithelial neoplasm	Homo sapiens	CVCL_0525
	SMMC-7721	Endocervical adenocarcinoma	Homo sapiens	CVCL_0534
In-vivo Model	Groups of HCT116-Luc-shCtrl, HCT116-Luc-shLINC00460, and HCT116-Luc-shLINC00460 + HMGA1 cells (5 × 106) were injected subcutaneously into the flanks of mice correspondingly.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[67]
Response Summary	N6-methyladenosine-modified hsa_circ_0087293 (SORE) sequestered miR-103a-2-5p and miR-660-3p by acting as a microRNA sponge, thereby competitively activating the Wnt/beta-catenin pathway and inducing sorafenib resistance in hepatocellular carcinoma.
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Responsed Drug	Sorafenib		Approved	Drug Info
Cell Process	Cell apoptosis
In-vitro Model	HCC sorafenib-resistant (SR) cell line HepG2-SR (Sorafenib-resistant HepG2 cell line)
	HCC sorafenib-resistant (SR) cell line Huh7-SR (Sorafenib-resistant Huh7 cell line)
	HCC sorafenib-resistant (SR) cell line LM3-SR (Sorafenib-resistant LM3 cell line)
	HCC sorafenib-resistant (SR) cell line SKhep1-SR (Sorafenib-resistant SKhep1 cell line)
In-vivo Model	The first CDX generation was constructed in 4-6 week-old male BALB/c nude mice and treated with sorafenib (30 mg/kg daily, oral gavage). Twelve weeks later, the most resistant xenograft was disaggregated and implanted subcutaneously into 4-6 week-old BALB/c nude mice as the second SR-CDX. Four weeks after implantation, the second SR-CDX mice were treated with sorafenib (30 mg/kg daily, oral gavage) and locally injected with sh-circRNA-SORE lentivirus or its negative control (twice a week for 2 weeks).

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[62]
Response Summary	hsa_circ_0092493 (circ_ARL3) is a critical regulator in HBV-related HCC, targeting the axis of circ-ARL3/miR-1305 can be a promising treatment for HBV+ HCC patients. HBx protein upregulated N6 -methyladenosine (m6A) methyltransferases METTL3 expression, increasing the m6A modification of circ-ARL3; then, m6A reader YTHDC1 bound to m6A-modified of circ-ARL3 and favored its reverse splicing and biogenesis. Furthermore, circ-ARL3 was able to sponge miR-1305, antagonizing the inhibitory effects of miR-1305 on a cohort of target oncogenes, thereby promoting HBV+ HCC progression.
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulator	YTH domain-containing protein 1 (YTHDC1)		READER	Regulator Info
Target Regulation	Up regulation
Cell Process	Reverse splicing and biogenesis
In-vitro Model	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
In-vivo Model	Mice were randomly divided into three groups, and subcutaneously injected with control, circ-ARL3-silenced and circ-ARL3&miR-1305-silenced HepG2.2.15 cells.
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[62]
Response Summary	hsa_circ_0092493 (circ_ARL3) is a critical regulator in HBV-related HCC, targeting the axis of circ-ARL3/miR-1305 can be a promising treatment for HBV+ HCC patients. HBx protein upregulated N6 -methyladenosine (m6A) methyltransferases METTL3 expression, increasing the m6A modification of circ-ARL3; then, m6A reader YTHDC1 bound to m6 A-modified of circ-ARL3 and favored its reverse splicing and biogenesis. Furthermore, circ-ARL3 was able to sponge miR-1305, antagonizing the inhibitory effects of miR-1305 on a cohort of target oncogenes, thereby promoting HBV+ HCC progression.
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Cell Process	Reverse splicing and biogenesis
In-vitro Model	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
In-vivo Model	Mice were randomly divided into three groups, and subcutaneously injected with control, circ-ARL3-silenced and circ-ARL3&miR-1305-silenced HepG2.2.15 cells.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[68]
Response Summary	N6-methyladenosine (m6A) motif was identified in the 353-357 region of YAP 3'UTR, and this m6A modification was essential for the interaction between miR-582-3p and YAP 3'UTR. And targeting Circ_104075 provides new strategies in HCC diagnosis and therapy.
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Cell Process	RNA stability
In-vitro Model	BEL-7402	Endocervical adenocarcinoma	Homo sapiens	CVCL_5492
	BEL-7404	Endocervical adenocarcinoma	Homo sapiens	CVCL_6568
	HEp-1	Cervical carcinoma	Homo sapiens	CVCL_JB76
	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
	L-02	Endocervical adenocarcinoma	Homo sapiens	CVCL_6926
	Huh-7	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0336
	SMMC-7721	Endocervical adenocarcinoma	Homo sapiens	CVCL_0534
	THLE-3	Normal	Homo sapiens	CVCL_3804
In-vivo Model	HNF4a knockout (HNF4a-/-) mice were generated using CRISPR/Cas9 in C57BL/6 mice.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[69]
Response Summary	Circ_DLC1, a downstream target of KIAA1429, is a promising prognostic marker for HCC patients, and the circDLC1-HuR-MMP1 axis serve as a potential therapeutic target for HCC treatment.
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulator	Protein virilizer homolog (VIRMA)		WRITER	Regulator Info
Target Regulation	Down regulation
Pathway Response	RNA degradation			hsa03018
Cell Process	RNA stability
In-vitro Model	SNU-449	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0454
	SK-HEP-1	Liver and intrahepatic bile duct epithelial neoplasm	Homo sapiens	CVCL_0525
	Huh-7	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0336
	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
	Hep 3B2.1-7	Childhood hepatocellular carcinoma	Homo sapiens	CVCL_0326
In-vivo Model	5 × 105 cells were injected subcutaneously into the right axilla of mice. Tumor volume was measured by a caliper weekly and calculated as length × width2 × 0.52. For the liver orthotopic-implanted models, each liver of mice was injected with 1 × 106 cells.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[70]
Response Summary	Driven by m6A modification, Circ_MAP3K4 encoded circMAP3K4-455aa, protected HCC cells from cisplatin exposure, and predicted worse prognosis of HCC patients. IGF2BP1 facilitates circMAP3K4 peptide translation, then the circMAP3K4 peptide inhibits AIF cleavage and nuclear distribution
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Responsed Drug	Cisplatin		Approved	Drug Info
Target Regulator	Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1)		READER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Ubiquitin mediated proteolysis			hsa04120
Cell Process	Proteasome pathway degradation
In-vitro Model	Huh-7	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0336
	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
	PLC/PRF/5	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0485

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[71]
Response Summary	circCPSF6 was dominated by ALKBH5-mediated demethylation, followed by the recognization and destabilization by YTHDF2. Meanwhile, circCPSF6 was upregulated in HCC specimens, and elevated hsa_circ_0000417 (circCPSF6) expression served as an independent prognostic factor for worse survival of patients with HCC.
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulator	RNA demethylase ALKBH5 (ALKBH5)		ERASER	Regulator Info
Cell Process	Cell proliferation
In-vitro Model	Hep 3B2.1-7	Childhood hepatocellular carcinoma	Homo sapiens	CVCL_0326
	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
	HCCLM3	Adult hepatocellular carcinoma	Homo sapiens	CVCL_6832
	MHCC97-H	Adult hepatocellular carcinoma	Homo sapiens	CVCL_4972
	B76.1/Huh7	Adult hepatocellular carcinoma	Homo sapiens	CVCL_U443
	SNU-449	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0454
	PLC/PRF/5	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0485
	L-02	Endocervical adenocarcinoma	Homo sapiens	CVCL_6926
In-vivo Model	HCC cells stably transfected with empty vector or circCPSF6 were subject to construct animal models, followed by the regular treatment of verteporfin, an inhibitor of YAP signaling.