m6A Regulator Information

General Information of the m6A Regulator (ID: REG00001)

Regulator Name	Fat mass and obesity-associated protein (FTO)
Synonyms	Alpha-ketoglutarate-dependent dioxygenase FTO; U6 small nuclear RNA (2'-O-methyladenosine-N(6)-)-demethylase FTO; U6 small nuclear RNA N(6)-methyladenosine-demethylase FTO; mRNA (2'-O-methyladenosine-N(6)-)-demethylase FTO; m6A(m)-demethylase FTO; mRNA N(6)-methyladenosine demethylase FTO; tRNA N1-methyl adenine demethylase FTO; KIAA1752 Click to Show/Hide
Gene Name	FTO
Sequence	MKRTPTAEEREREAKKLRLLEELEDTWLPYLTPKDDEFYQQWQLKYPKLILREASSVSEE LHKEVQEAFLTLHKHGCLFRDLVRIQGKDLLTPVSRILIGNPGCTYKYLNTRLFTVPWPV KGSNIKHTEAEIAAACETFLKLNDYLQIETIQALEELAAKEKANEDAVPLCMSADFPRVG MGSSYNGQDEVDIKSRAAYNVTLLNFMDPQKMPYLKEEPYFGMGKMAVSWHHDENLVDRS AVAVYSYSCEGPEEESEDDSHLEGRDPDIWHVGFKISWDIETPGLAIPLHQGDCYFMLDD LNATHQHCVLAGSQPRFSSTHRVAECSTGTLDYILQRCQLALQNVCDDVDNDDVSLKSFE PAVLKQGEEIHNEVEFEWLRQFWFQGNRYRKCTDWWCQPMAQLEALWKKMEGVTNAVLHE VKREGLPVEQRNEILTAILASLTARQNLRREWHARCQSRIARTLPADQKPECRPYWEKDD ASMPLPFDLTDIVSELRGQLLEAKP Click to Show/Hide
Family	fto family
Function	RNA demethylase that mediates oxidative demethylation of different RNA species, such as mRNAs, tRNAs and snRNAs, and acts as a regulator of fat mass, adipogenesis and energy homeostasis . Specifically demethylates N(6)-methyladenosine (m6A) RNA, the most prevalent internal modification of messenger RNA (mRNA) in higher eukaryotes . M6A demethylation by FTO affects mRNA expression and stability . Also able to demethylate m6A in U6 small nuclear RNA (snRNA). Mediates demethylation of N(6),2'-O-dimethyladenosine cap (m6A(m)), by demethylating the N(6)-methyladenosine at the second transcribed position of mRNAs and U6 snRNA . Demethylation of m6A(m) in the 5'-cap by FTO affects mRNA stability by promoting susceptibility to decapping . Also acts as a tRNA demethylase by removing N(1)-methyladenine from various tRNAs . Has no activity towards 1-methylguanine . Has no detectable activity towards double-stranded DNA . Also able to repair alkylated DNA and RNA by oxidative demethylation: demethylates single-stranded RNA containing 3-methyluracil, single-stranded DNA containing 3-methylthymine and has low demethylase activity towards single-stranded DNA containing 1-methyladenine or 3-methylcytosine . Ability to repair alkylated DNA and RNA is however unsure in vivo. Involved in the regulation of fat mass, adipogenesis and body weight, thereby contributing to the regulation of body size and body fat accumulation . Involved in the regulation of thermogenesis and the control of adipocyte differentiation into brown or white fat cells. Regulates activity of the dopaminergic midbrain circuitry via its ability to demethylate m6A in mRNAs (By similarity). Plays an oncogenic role in a number of acute myeloid leukemias by enhancing leukemic oncogene-mediated cell transformation: acts by mediating m6A demethylation of target transcripts such as MYC, CEBPA, ASB2 and RARA, leading to promote their expression. Click to Show/Hide
Gene ID	79068
Uniprot ID	FTO_HUMAN
Regulator Type	WRITER ERASER READER
Mechanism Diagram	Click to View the Original Diagram

Target Genes	Click to View Potential Target Genes of This Regulator

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

FTO can regulate the m6A methylation of following target genes, and result in corresponding disease/drug response(s). You can browse corresponding disease or drug response(s) resulted from the regulation of certain target gene.

Browse Target Gene related Disease

Browse Target Gene related Drug

ADP-ribosylation factor-like protein 5B (ARL5B)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by FTO*
Cell Line	253J cell line	Homo sapiens
Treatment: siFTO 253J cells Control: 253J cells		GSE150239
Regulation		logFC: 7.32E-01 p-value: 5.39E-08
More Results	Click to View More RNA-seq Results

Breast cancer [ICD-11: 2C60]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[1]
Responsed Disease	Breast cancer [ICD-11: 2C60]
Target Regulation	Up regulation
Cell Process	Cell invasion and migration
In-vitro Model	T-47D	Invasive breast carcinoma	Homo sapiens	CVCL_0553
	SK-BR-3	Breast adenocarcinoma	Homo sapiens	CVCL_0033
	MDA-MB-453	Breast adenocarcinoma	Homo sapiens	CVCL_0418
	MDA-MB-231	Breast adenocarcinoma	Homo sapiens	CVCL_0062
	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
	MCF-10A	Normal	Homo sapiens	CVCL_0598
	BT-549	Invasive breast carcinoma	Homo sapiens	CVCL_1092
	BT-474	Invasive breast carcinoma	Homo sapiens	CVCL_0179
Response Summary	FTO up-regulated ADP-ribosylation factor-like protein 5B (ARL5B) by inhibiting miR-181b-3p. The carcinogenic activity of FTO in promoting the invasion and migration of breast cancer cells via the FTO/miR-181b-3p/ARL5B signaling pathway.

Ankyrin repeat and SOCS box protein 2 (ASB2)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by FTO*
Cell Line	NB4 cell line	Homo sapiens
Treatment: shFTO NB4 cells Control: shNS NB4 cells		GSE103494
Regulation		logFC: 8.19E-01 p-value: 3.80E-03
More Results	Click to View More RNA-seq Results

Acute myeloid leukaemia [ICD-11: 2A60]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[2]
Responsed Disease	Acute myeloid leukaemia [ICD-11: 2A60]
Responsed Drug	Tretinoin		Approved	Drug Info
Target Regulation	Down regulation
Cell Process	RNA stability
Cell Process	RNA degradation (hsa03018)
In-vitro Model	K-562	Chronic myelogenous leukemia	Homo sapiens	CVCL_0004
	KOCL-48	Childhood acute monocytic leukemia	Homo sapiens	CVCL_6867
	Mono-Mac-6	Adult acute monocytic leukemia	Homo sapiens	CVCL_1426
Response Summary	FTO enhances leukemic oncogene-mediated cell transformation and leukemogenesis, and inhibits all-trans-retinoic acid (ATRA)-induced AML cell differentiation, through regulating expression of targets such as Ankyrin repeat and SOCS box protein 2 (ASB2) and RARA by reducing m6A levels in these mRNA transcripts.

Apolipoprotein E (APOE)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by FTO*
Cell Line	NB4 cell line	Homo sapiens
Treatment: shFTO NB4 cells Control: shNS NB4 cells		GSE103494
Regulation		logFC: 1.26E+00 p-value: 1.34E-03
More Results	Click to View More RNA-seq Results

Thyroid Cancer [ICD-11: 2D10]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[3]
Responsed Disease	Papillary thyroid cancer [ICD-11: 2D10.1]
Target Regulation	Down regulation
Pathway Response	JAK-STAT signaling pathway			hsa04630
Pathway Response	Glycolysis / Gluconeogenesis			hsa00010
Cell Process	Glycolysis
In-vitro Model	TPC-1	Thyroid gland papillary carcinoma	Homo sapiens	CVCL_6298
	Nthy-ori 3-1	Normal	Homo sapiens	CVCL_2659
	K1	Thyroid gland papillary carcinoma	Homo sapiens	CVCL_2537
	IHH-4	Thyroid gland papillary carcinoma	Homo sapiens	CVCL_2960
	B-CPAP	Thyroid gland carcinoma	Homo sapiens	CVCL_0153
Response Summary	FTO acts as a tumor suppressor to inhibit tumor glycolysis in Papillary thyroid cancer(PTC). FTO/Apolipoprotein E (APOE) axis inhibits PTC glycolysis by modulating IL-6/JAK2/STAT3 signaling pathway.

Apoptosis regulator Bcl-2 (BCL2)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by FTO*
Cell Line	NB4 cell line	Homo sapiens
Treatment: shFTO NB4 cells Control: shNS NB4 cells		GSE103494
Regulation		logFC: -6.55E-01 p-value: 1.57E-02
More Results	Click to View More RNA-seq Results

Breast cancer [ICD-11: 2C60]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[4]
Responsed Disease	Breast cancer [ICD-11: 2C60]
Pathway Response	Apoptosis	hsa04210
	PI3K-Akt signaling pathway	hsa04151
Cell Process	Cell proliferation
	Cell apoptosis
Response Summary	Studies of the aberrant expression of m6A mediators in breast cancer revealed that they were associated with different BC subtypes and functions, such as proliferation, apoptosis, stemness, the cell cycle, migration, and metastasis, through several factors and signaling pathways, such as Apoptosis regulator Bcl-2 (BCL2) and the PI3K/Akt pathway, among others. Fat mass and obesity-associated protein (FTO) was identified as the first m6A demethylase, and a series of inhibitors that target FTO were reported to have potential for the treatment of BC by inhibiting cell proliferation and promoting apoptosis.

ATP-binding cassette sub-family C member 10 (ABCC10)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by FTO*
Cell Line	Mouse hippocampus	Mus musculus
Treatment: FTO knockout mice hippocampus Control: Wild type hippocampus		GSE94098
Regulation		logFC: 6.58E-01 p-value: 2.09E-04
More Results	Click to View More RNA-seq Results

Lung cancer [ICD-11: 2C25]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[5]
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Responsed Drug	Gefitinib		Approved	Drug Info
Target Regulation	Up regulation
Pathway Response	ABC transporters			hsa02010
In-vitro Model	PC-9	Lung adenocarcinoma	Homo sapiens	CVCL_B260
In-vitro Model	NCI-H1975	Lung adenocarcinoma	Homo sapiens	CVCL_1511
In-vivo Model	Mice were randomized into three groups (n = 7/group), 1 × 10⁷ PC9 cells absorbed exosomes were subcutaneously injected into the Bilateral groin of mice. Treatment began 1 week following injection, the mice were intraperitoneally injected with gefitinib (30 mg/kg/day).
Response Summary	Not only FTO knockdown enhanced the gefitinib sensitivity of GR cells but also FTO reduction in donor exosomes alleviated the acquired resistance of recipient non-small cell lung cancer PC9 cells. FTO/YTHDF2/ATP-binding cassette sub-family C member 10 (ABCC10) axis played a role in intercellular transmission of GR cell-derived exosome-mediated gefitinib resistance.

BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by FTO*
Cell Line	253J cell line	Homo sapiens
Treatment: siFTO 253J cells Control: 253J cells		GSE150239
Regulation		logFC: 3.13E+00 p-value: 6.97E-04
More Results	Click to View More RNA-seq Results

Breast cancer [ICD-11: 2C60]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[6]
Responsed Disease	Breast cancer [ICD-11: 2C60]
Target Regulation	Up regulation
Cell Process	Cell proliferation
	Cell colony formation
	Cell metastasis
In-vitro Model	4 T1 (Mouse breast cancer cells)
	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
	MDA-MB-231	Breast adenocarcinoma	Homo sapiens	CVCL_0062
In-vivo Model	For the subcutaneous implantation model, 5 4-week-old female Balb/c mice were randomly grouped and injected with 1 × 10⁶ shCtrl, shFTO or shFTO/shBNIP3 KD 4 T1 cells. For tumor metastasis mouse model, 5 4-week-old female Balb/c mice were randomly grouped and injected with 1 × 106 shCtrl, shFTO or shFTO/shBNIP3 KD 4 T1 cells via tail vein. For orthotopic xenograft mouse model, 5 4-week-old female NOD/SCID mice were randomly grouped.
Response Summary	FTO mediated m6A demethylation in the 3'UTR of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3) mRNA and induced its degradation via an YTHDF2 independent mechanism. FTO serves as a novel potential therapeutic target for breast cancer.

C-X-C chemokine receptor type 4 (CXCR4)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by FTO*
Cell Line	NB4 cell line	Homo sapiens
Treatment: shFTO NB4 cells Control: shNS NB4 cells		GSE103494
Regulation		logFC: 9.72E-01 p-value: 3.86E-03
More Results	Click to View More RNA-seq Results

Melanoma [ICD-11: 2C30]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[7]
Responsed Disease	Melanoma [ICD-11: 2C30]
Responsed Drug	PMID31239444-anti-PD1 antibody		Investigative	Drug Info
Target Regulation	Up regulation
Pathway Response	PD-L1 expression and PD-1 checkpoint pathway in cancer			hsa05235
Cell Process	mRNA decay
In-vitro Model	B16-F10	Mouse melanoma	Mus musculus	CVCL_0159
	CHL-1	Melanoma	Homo sapiens	CVCL_1122
	624-mel	Melanoma	Homo sapiens	CVCL_8054
	NHEM (Normal Human Epidermal Melanocytes)
	SK-MEL-30	Cutaneous melanoma	Homo sapiens	CVCL_0039
	WM115	Melanoma	Homo sapiens	CVCL_0040
	WM35	Melanoma	Homo sapiens	CVCL_0580
	WM3670	Melanoma	Homo sapiens	CVCL_6799
	WM793	Melanoma	Homo sapiens	CVCL_8787
In-vivo Model	When the tumors reached a volume of 80-100 mm³, mice were treated with anti-PD-1 or isotype control antibody (200 ug/mouse) by i.p. injection, every other day for three times. For IFNγ blockade treatment, C57BL/6 mice were treated with anti-IFNγ antibody or isotype control IgG (250 ug/mouse) every other day after tumor cell inoculation.
Response Summary	These findings demonstrate a crucial role of FTO as an m6A demethylase in promoting melanoma tumorigenesis and anti-PD-1 resistance, and suggest that the combination of FTO inhibition with anti-PD-1 blockade reduces the resistance to immunotherapy in melanoma. Knockdown of FTO increases m6A methylation in the critical protumorigenic melanoma cell-intrinsic genes including PD-1 (PDCD1), C-X-C chemokine receptor type 4 (CXCR4), and SOX10, leading to increased RNA decay through the m6A reader YTHDF2.

Caveolin-1 (CAV1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by FTO*
Cell Line	253J cell line	Homo sapiens
Treatment: siFTO 253J cells Control: 253J cells		GSE150239
Regulation		logFC: 3.45E+00 p-value: 8.00E-05
More Results	Click to View More RNA-seq Results

Gastric cancer [ICD-11: 2B72]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[8]
Responsed Disease	Gastric cancer [ICD-11: 2B72]
Target Regulation	Down regulation
In-vitro Model	SGC-7901	Gastric carcinoma	Homo sapiens	CVCL_0520
In-vitro Model	AGS	Gastric adenocarcinoma	Homo sapiens	CVCL_0139
In-vivo Model	For the tumor growth analysis, AGS cells were subcutaneously injected into nude mice, and then the tumor volumes were monitored every 5 days. Tumor volumes were estimated based on the length and width and calculated using the following formula: tumor volume = (length × width2)/2. About 1 month later, the nude mice were sacrificed, and then tumors were excised, pictured, and weighed. For the tumor metastasis analysis, AGS cells were injected into nude mice by Tail Vein. About 1 month later, the nude mice were sacrificed, and then lung with metastasis lesions were excised, pictured, and counted.
Response Summary	This study demonstrated that the key demethylase of m6A FTO promoted the proliferation and metastasis of gastric cancer via regulating the mitochondrial fission/fusion and metabolism. In terms of mechanism, FTO improved the degradation of Caveolin-1 (CAV1) mRNA via its demethylation

CCAAT/enhancer-binding protein alpha (CEBPA)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by FTO*
Cell Line	NB4 cell line	Homo sapiens
Treatment: shFTO NB4 cells Control: shNS NB4 cells		GSE103494
Regulation		logFC: 6.07E-01 p-value: 3.92E-03
More Results	Click to View More RNA-seq Results

Brain cancer [ICD-11: 2A00]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[9]
Responsed Disease	Glioma [ICD-11: 2A00.0]
Responsed Drug	R-2HG		Investigative	Drug Info
Target Regulation	Down regulation
Cell Process	Glutamine metabolism
Cell Process	Cell apoptosis
In-vitro Model	8-MG-BA	Glioblastoma	Homo sapiens	CVCL_1052
	A-172	Glioblastoma	Homo sapiens	CVCL_0131
	DK-MG	Glioblastoma	Homo sapiens	CVCL_1173
	GaMG	Glioblastoma	Homo sapiens	CVCL_1226
	HEL	Erythroleukemia	Homo sapiens	CVCL_0001
	Jurkat	T acute lymphoblastic leukemia	Homo sapiens	CVCL_0065
	KOCL-45	B acute lymphoblastic leukemia	Homo sapiens	CVCL_3993
	KOCL-48	Childhood acute monocytic leukemia	Homo sapiens	CVCL_6867
	KOCL-50	B acute lymphoblastic leukemia	Homo sapiens	CVCL_6866
	KOCL-51	B acute lymphoblastic leukemia	Homo sapiens	CVCL_6865
	KOCL-69	B acute lymphoblastic leukemia	Homo sapiens	CVCL_3995
	KOPN-1	B acute lymphoblastic leukemia	Homo sapiens	CVCL_3937
	LN-18	Glioblastoma	Homo sapiens	CVCL_0392
	LN-229	Glioblastoma	Homo sapiens	CVCL_0393
	MA9.3 (MA9.3)
	MA9.6ITD (MLL-AF9 plus FLT3-ITD)
	MA9.6RAS (MLL-AF9 plus NRasG12D)
	MA9.6 (MLL-AF9)
	MA9.6ITD (MLL-AF9 plus FLT3-ITD)
	MA9.6RAS (MLL-AF9 plus NRasG12D)
	ME-1 [Human leukemia]	Adult acute myeloid leukemia	Homo sapiens	CVCL_2110
	ML-2	Adult acute myeloid leukemia	Homo sapiens	CVCL_1418
	MV4-11	Childhood acute monocytic leukemia	Homo sapiens	CVCL_0064
	NB4	Acute promyelocytic leukemia	Homo sapiens	CVCL_0005
	NOMO-1	Adult acute monocytic leukemia	Homo sapiens	CVCL_1609
	PL21	Familial adenomatous polyposis	Homo sapiens	CVCL_JM48
	T98G	Glioblastoma	Homo sapiens	CVCL_0556
	THP-1	Childhood acute monocytic leukemia	Homo sapiens	CVCL_0006
	U-87MG ATCC	Glioblastoma	Homo sapiens	CVCL_0022
	U-937	Adult acute monocytic leukemia	Homo sapiens	CVCL_0007
In-vivo Model	For R-2HG injection mouse models, sensitive (NOMO-1 and MA9.3ITD) or resistant (MA9.3RAS) cells were injected into NSGS or NRGS intravenously, and then R-2HG (6mg/kg body weight) or PBS were injected once daily through tail vein for 12 consecutive days starting from day 11 post xeno-transplantation.
Response Summary	This work demonstrates anti-tumor effects of 2HG in inhibiting proliferation/survival of FTO-high cancer cells via targeting FTO/m6A/MYC/CCAAT/enhancer-binding protein alpha (CEBPA) signaling.High levels of FTO sensitize leukemia cells to R-2HG, whereas hyperactivation of MYC signaling confers resistance that can be reversed by the inhibition of MYC signaling. R-2HG also displays anti-tumor activity in glioma. High levels of FTO sensitize leukemic cells to R-2HG, whereas hyperactivation of MYC signaling confers resistance that can be reversed by the inhibition of MYC signaling.

Malignant haematopoietic neoplasm [ICD-11: 2B33]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[9]
Responsed Disease	Leukaemia [ICD-11: 2B33.4]
Responsed Drug	R-2HG		Investigative	Drug Info
Target Regulation	Down regulation
Cell Process	Glutamine metabolism
Cell Process	Cell apoptosis
In-vitro Model	8-MG-BA	Glioblastoma	Homo sapiens	CVCL_1052
	A-172	Glioblastoma	Homo sapiens	CVCL_0131
	DK-MG	Glioblastoma	Homo sapiens	CVCL_1173
	GaMG	Glioblastoma	Homo sapiens	CVCL_1226
	HEL	Erythroleukemia	Homo sapiens	CVCL_0001
	Jurkat	T acute lymphoblastic leukemia	Homo sapiens	CVCL_0065
	KOCL-45	B acute lymphoblastic leukemia	Homo sapiens	CVCL_3993
	KOCL-48	Childhood acute monocytic leukemia	Homo sapiens	CVCL_6867
	KOCL-50	B acute lymphoblastic leukemia	Homo sapiens	CVCL_6866
	KOCL-51	B acute lymphoblastic leukemia	Homo sapiens	CVCL_6865
	KOCL-69	B acute lymphoblastic leukemia	Homo sapiens	CVCL_3995
	KOPN-1	B acute lymphoblastic leukemia	Homo sapiens	CVCL_3937
	LN-18	Glioblastoma	Homo sapiens	CVCL_0392
	LN-229	Glioblastoma	Homo sapiens	CVCL_0393
	MA9.3 (MA9.3)
	MA9.6ITD (MLL-AF9 plus FLT3-ITD)
	MA9.6RAS (MLL-AF9 plus NRasG12D)
	MA9.6 (MLL-AF9)
	MA9.6ITD (MLL-AF9 plus FLT3-ITD)
	MA9.6RAS (MLL-AF9 plus NRasG12D)
	ME-1 [Human leukemia]	Adult acute myeloid leukemia	Homo sapiens	CVCL_2110
	ML-2	Adult acute myeloid leukemia	Homo sapiens	CVCL_1418
	MV4-11	Childhood acute monocytic leukemia	Homo sapiens	CVCL_0064
	NB4	Acute promyelocytic leukemia	Homo sapiens	CVCL_0005
	NOMO-1	Adult acute monocytic leukemia	Homo sapiens	CVCL_1609
	PL21	Familial adenomatous polyposis	Homo sapiens	CVCL_JM48
	T98G	Glioblastoma	Homo sapiens	CVCL_0556
	THP-1	Childhood acute monocytic leukemia	Homo sapiens	CVCL_0006
	U-87MG ATCC	Glioblastoma	Homo sapiens	CVCL_0022
	U-937	Adult acute monocytic leukemia	Homo sapiens	CVCL_0007
In-vivo Model	For R-2HG injection mouse models, sensitive (NOMO-1 and MA9.3ITD) or resistant (MA9.3RAS) cells were injected into NSGS or NRGS intravenously, and then R-2HG (6mg/kg body weight) or PBS were injected once daily through tail vein for 12 consecutive days starting from day 11 post xeno-transplantation.
Response Summary	This work demonstrates anti-tumor effects of 2HG in inhibiting proliferation/survival of FTO-high cancer cells via targeting FTO/m6A/MYC/CCAAT/enhancer-binding protein alpha (CEBPA) signaling.High levels of FTO sensitize leukemia cells to R-2HG, whereas hyperactivation of MYC signaling confers resistance that can be reversed by the inhibition of MYC signaling. R-2HG also displays anti-tumor activity in glioma. High levels of FTO sensitize leukemic cells to R-2HG, whereas hyperactivation of MYC signaling confers resistance that can be reversed by the inhibition of MYC signaling.

Cell death activator CIDE-3 (CIDEC)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by FTO*
Cell Line	Mouse liver	Mus musculus
Treatment: FTO knockout mouse liver tissue Control: Wild type mouse liver tissue		GSE125785
Regulation		logFC: -2.15E+00 p-value: 6.18E-03
More Results	Click to View More RNA-seq Results

Non-alcoholic fatty liver disease [ICD-11: DB92]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[10]
Responsed Disease	Non-alcoholic fatty liver disease [ICD-11: DB92]
Target Regulation	Up regulation
Cell Process	Lipogenesis
In-vitro Model	HEK293T	Normal	Homo sapiens	CVCL_0063
In-vitro Model	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
In-vivo Model	After being fed with high-fat diet for 4 weeks, mice were given twice vena caudalis injection of control siRNA or Cidec siRNA (50 ug/mouse) mixed with liposome. Liposomes were prepared as described elsewhere.
Response Summary	FTO increased the lipid accumulation in hepatocytes by increasing nuclear translocation of SREBP1c and SREBP1c maturation, thus improving the transcriptional activity of LD-associated protein Cell death activator CIDE-3 (CIDEC).The studies provide new mechanistic insight into nonalcoholic fatty liver disease (NAFLD) mediated by FTO.

Collagenase 3 (MMP13)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by FTO*
Cell Line	253J cell line	Homo sapiens
Treatment: siFTO 253J cells Control: 253J cells		GSE150239
Regulation		logFC: 2.41E+00 p-value: 4.00E-03
More Results	Click to View More RNA-seq Results

Oral cavity/oesophagus/stomach in situ carcinoma [ICD-11: 2E60]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[11]
Responsed Disease	Esophageal squamous cell carcinoma [ICD-11: 2B70.1]
Target Regulation	Up regulation
Cell Process	Cell growth and migration
In-vitro Model	Eca-109	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_6898
	KYSE-150	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1348
	TE-1	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1759
In-vivo Model	Stable down-regulated FTO cells were prepared in Eca-109 and KYSE150 and subcutaneously injected into the flank of nude mouse with 2 × 10⁶ cells per mouse.
Response Summary	Up-regulation of FTO is frequently observed in esophageal squamous cell carcinoma tissues, and FTO facilitates cell proliferation and migration in ESCC by up-regulating Collagenase 3 (MMP13).

Cyclic AMP-dependent transcription factor ATF-4 (ATF4)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by FTO*
Cell Line	253J cell line	Homo sapiens
Treatment: siFTO 253J cells Control: 253J cells		GSE150239
Regulation		logFC: -1.42E+00 p-value: 2.68E-47
More Results	Click to View More RNA-seq Results

Colorectal cancer [ICD-11: 2B91]

In total 6 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[12]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Responsed Drug	Asparagine inhibitor		Approved	Drug Info
Pathway Response	mTOR signaling pathway			hsa04150
Cell Process	RNA decay
	Cell growth and death
	Cell autophagy
In-vitro Model	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
Response Summary	In colorectal cancer, Glutaminolysis inhibition upregulated ATF4 expression in an m6A-dependent manner to activate pro-survival autophagy through transcriptional activation of the mTOR inhibitor DDIT4. Determined the relationship between FTO alpha-ketoglutarate dependent dioxygenase (FTO), YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), and ATF4. ATF4 transcriptionally upregulated DDIT4 to suppress Cyclic AMP-dependent transcription factor ATF-4 (ATF4), which induced pro-survival autophagy during glutaminolysis inhibition.
Experiment 2 Reporting the m6A-centered Disease Response of This Target Gene				[12]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Responsed Drug	Chloroquine		Approved	Drug Info
Pathway Response	mTOR signaling pathway			hsa04150
Cell Process	RNA decay
	Cell growth and death
	Cell autophagy
In-vitro Model	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
Response Summary	In colorectal cancer, Glutaminolysis inhibition upregulated ATF4 expression in an m6A-dependent manner to activate pro-survival autophagy through transcriptional activation of the mTOR inhibitor DDIT4. Determined the relationship between FTO alpha-ketoglutarate dependent dioxygenase (FTO), YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), and ATF4. ATF4 transcriptionally upregulated DDIT4 to suppress Cyclic AMP-dependent transcription factor ATF-4 (ATF4), which induced pro-survival autophagy during glutaminolysis inhibition.
Experiment 3 Reporting the m6A-centered Disease Response of This Target Gene				[12]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Responsed Drug	Meclofenamate sodium		Approved	Drug Info
Pathway Response	mTOR signaling pathway			hsa04150
Cell Process	RNA decay
	Cell growth and death
	Cell autophagy
In-vitro Model	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
Response Summary	In colorectal cancer, Glutaminolysis inhibition upregulated ATF4 expression in an m6A-dependent manner to activate pro-survival autophagy through transcriptional activation of the mTOR inhibitor DDIT4. Determined the relationship between FTO alpha-ketoglutarate dependent dioxygenase (FTO), YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), and ATF4. Cyclic AMP-dependent transcription factor ATF-4 (ATF4) transcriptionally upregulated DDIT4 to suppress mTOR, which induced pro-survival autophagy during glutaminolysis inhibition.
Experiment 4 Reporting the m6A-centered Disease Response of This Target Gene				[12]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Responsed Drug	Rapamycin		Approved	Drug Info
Pathway Response	mTOR signaling pathway			hsa04150
Cell Process	RNA decay
	Cell growth and death
	Cell autophagy
In-vitro Model	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
Response Summary	In colorectal cancer, Glutaminolysis inhibition upregulated ATF4 expression in an m6A-dependent manner to activate pro-survival autophagy through transcriptional activation of the mTOR inhibitor DDIT4. Determined the relationship between FTO alpha-ketoglutarate dependent dioxygenase (FTO), YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), and ATF4. Cyclic AMP-dependent transcription factor ATF-4 (ATF4) transcriptionally upregulated DDIT4 to suppress mTOR, which induced pro-survival autophagy during glutaminolysis inhibition.
Experiment 5 Reporting the m6A-centered Disease Response of This Target Gene				[12]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Responsed Drug	CB-839		Phase 2	Drug Info
Pathway Response	mTOR signaling pathway			hsa04150
Cell Process	RNA decay
	Cell growth and death
	Cell autophagy
In-vitro Model	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
Response Summary	In colorectal cancer, Glutaminolysis inhibition upregulated ATF4 expression in an m6A-dependent manner to activate pro-survival autophagy through transcriptional activation of the mTOR inhibitor DDIT4. Determined the relationship between FTO alpha-ketoglutarate dependent dioxygenase (FTO), YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), and ATF4. Cyclic AMP-dependent transcription factor ATF-4 (ATF4) transcriptionally upregulated DDIT4 to suppress mTOR, which induced pro-survival autophagy during glutaminolysis inhibition.
Experiment 6 Reporting the m6A-centered Disease Response of This Target Gene				[12]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Responsed Drug	GLS-IN-968		Investigative	Drug Info
Pathway Response	mTOR signaling pathway			hsa04150
Cell Process	RNA decay
	Cell growth and death
	Cell autophagy
In-vitro Model	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
Response Summary	In colorectal cancer, Glutaminolysis inhibition upregulated ATF4 expression in an m6A-dependent manner to activate pro-survival autophagy through transcriptional activation of the mTOR inhibitor DDIT4. Determined the relationship between FTO alpha-ketoglutarate dependent dioxygenase (FTO), YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), and ATF4. ATF4 transcriptionally upregulated DDIT4 to suppress Cyclic AMP-dependent transcription factor ATF-4 (ATF4), which induced pro-survival autophagy during glutaminolysis inhibition.

Cyclin-A2 (CCNA2)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by FTO*
Cell Line	Cerebral cortex	Mus musculus
Treatment: METTL3 (f/f, Emx1-cre) cerebral cortex Control: Wild type cerebral cortex		GSE154992
Regulation		logFC: 7.89E-01 p-value: 6.22E-11
More Results	Click to View More RNA-seq Results

Obesity [ICD-11: 5B81]

In total 2 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[13]
Responsed Disease	Obesity [ICD-11: 5B81]
Responsed Drug	Epigallocatechin gallate		Phase 3	Drug Info
Target Regulation	Up regulation
Pathway Response	Cell cycle			hsa04110
Cell Process	Adipogenesis
In-vitro Model	3T3-L1	Normal	Mus musculus	CVCL_0123
Response Summary	m6A-dependent Cyclin-A2 (CCNA2) and CDK2 expressions mediated by FTO and YTHDF2 contributed to EGCG-induced adipogenesis inhibition.
Experiment 2 Reporting the m6A-centered Disease Response of This Target Gene				[14]
Responsed Disease	Obesity [ICD-11: 5B81]
Pathway Response	Cell cycle			hsa04110
Cell Process	Adipogenesis
	Arrest cell cycle at S phase
In-vitro Model	3T3-L1	Normal	Mus musculus	CVCL_0123
Response Summary	FTO knockdown markedly decreased the expression of Cyclin-A2 (CCNA2) and CDK2, crucial cell cycle regulators, leading to delayed entry of MDI-induced cells into G2 phase. m6A-binding protein YTHDF2 recognized and decayed methylated mRNAs of CCNA2 and CDK2, leading to decreased protein expression, thereby prolonging cell cycle progression and suppressing adipogenesis. The adipocyte life cycle, including proliferation and adipogenesis, has become a potential target for many bioactive compounds and drugs for the prevention and treatment of obesity.

Cyclin-dependent kinase 2 (CDK2)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by FTO*
Cell Line	B16-OVA cell line	Mus musculus
Treatment: shFTO B16-OVA cells Control: shNC B16-OVA cells		GSE154952
Regulation		logFC: 7.39E-01 p-value: 1.49E-28
More Results	Click to View More RNA-seq Results

Obesity [ICD-11: 5B81]

In total 2 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[13]
Responsed Disease	Obesity [ICD-11: 5B81]
Responsed Drug	Epigallocatechin gallate		Phase 3	Drug Info
Target Regulation	Up regulation
Pathway Response	Cell cycle			hsa04110
Cell Process	Adipogenesis
In-vitro Model	3T3-L1	Normal	Mus musculus	CVCL_0123
Response Summary	m6A-dependent CCNA2 and Cyclin-dependent kinase 2 (CDK2) expressions mediated by FTO and YTHDF2 contributed to EGCG-induced adipogenesis inhibition.
Experiment 2 Reporting the m6A-centered Disease Response of This Target Gene				[14]
Responsed Disease	Obesity [ICD-11: 5B81]
Pathway Response	Cell cycle			hsa04110
Cell Process	Adipogenesis
	Arrest cell cycle at S phase
In-vitro Model	3T3-L1	Normal	Mus musculus	CVCL_0123
Response Summary	FTO knockdown markedly decreased the expression of CCNA2 and Cyclin-dependent kinase 2 (CDK2), crucial cell cycle regulators, leading to delayed entry of MDI-induced cells into G2 phase. m6A-binding protein YTHDF2 recognized and decayed methylated mRNAs of CCNA2 and CDK2, leading to decreased protein expression, thereby prolonging cell cycle progression and suppressing adipogenesis. The adipocyte life cycle, including proliferation and adipogenesis, has become a potential target for many bioactive compounds and drugs for the prevention and treatment of obesity.

Cyclin-dependent kinase inhibitor 1 (CDKN1A)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by FTO*
Cell Line	253J cell line	Homo sapiens
Treatment: siFTO 253J cells Control: 253J cells		GSE150239
Regulation		logFC: 9.72E-01 p-value: 1.24E-24
More Results	Click to View More RNA-seq Results

Oral cavity/oesophagus/stomach in situ carcinoma [ICD-11: 2E60]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[16]
Responsed Disease	Esophageal squamous cell carcinoma [ICD-11: 2B70.1]
Pathway Response	Cell cycle			hsa04110
Pathway Response	Ubiquitin mediated proteolysis			hsa04120
Cell Process	Ubiquitination degradation
	Cell apoptosis
	Decreased G0/G1 phase
In-vitro Model	HET-1A	Normal	Homo sapiens	CVCL_3702
	KYSE-150	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1348
	KYSE-450	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1353
	KYSE-70	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1356
	TE-1	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1759
In-vivo Model	The number of cells inoculated in each mouse was 4 × 10⁶, 1 × 10⁶, 2 × 10⁶ and 1 × 10⁶, respectively.
Response Summary	The elevated FTO in esophageal squamous cell carcinoma decreased m6A methylation of LINC00022 transcript, leading to the inhibition of LINC00022 decay via the m6A reader YTHDF2. LINC00022 directly binds to Cyclin-dependent kinase inhibitor 1 (CDKN1A) protein and promotes its ubiquitination-mediated degradation, thereby facilitating cell-cycle progression and proliferation.

Dapper homolog 1 (DACT1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by FTO*
Cell Line	Mouse liver	Mus musculus
Treatment: FTO knockout mouse liver tissue Control: Wild type mouse liver tissue		GSE125785
Regulation		logFC: 1.21E+00 p-value: 4.60E-03
More Results	Click to View More RNA-seq Results

Osteosarcoma [ICD-11: 2B51]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[17]
Responsed Disease	Osteosarcoma [ICD-11: 2B51]
Target Regulation	Down regulation
Pathway Response	Wnt signaling pathway	hsa04310
Response Summary	FTO could reduce the mRNA stability of Dapper homolog 1 (DACT1) via m6A demethylation, which decreased DACT1 expression and further activated the Wnt signaling pathway. The oncogenic effect of FTO on osteosarcoma was dependent on DACT1.

Diacylglycerol O-acyltransferase 2 (DGAT2)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by FTO*
Cell Line	B16-OVA cell line	Mus musculus
Treatment: shFTO B16-OVA cells Control: shNC B16-OVA cells		GSE154952
Regulation		logFC: -6.69E-01 p-value: 1.09E-02
More Results	Click to View More RNA-seq Results

Diabetes [ICD-11: 5A10-5A14]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[18]
Responsed Disease	Diabetes [ICD-11: 5A10-5A14]
Pathway Response	Metabolic pathways			hsa01100
Cell Process	Lipid metabolism
In-vitro Model	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
Response Summary	Glucose Is Involved in the Dynamic Regulation of m6A in Patients With Type 2 Diabetes.high-glucose stimulation enhances FTO expression, which leads to decreased m6A, and the lower m6A induces methyltransferase upregulation; FTO then triggers the mRNA expression of FOXO1, FASN, G6PC, and Diacylglycerol O-acyltransferase 2 (DGAT2), and these four genes were correlated with glucose and lipid metabolism.

DNA damage-inducible transcript 3 protein (DDIT3/CHOP)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by FTO*
Cell Line	NB4 cell line	Homo sapiens
Treatment: shFTO NB4 cells Control: shNS NB4 cells		GSE103494
Regulation		logFC: 7.94E-01 p-value: 7.54E-04
More Results	Click to View More RNA-seq Results

Gastric cancer [ICD-11: 2B72]

In total 3 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[19]
Responsed Disease	Gastric cancer [ICD-11: 2B72]
Responsed Drug	Cisplatin		Approved	Drug Info
Target Regulation	Down regulation
Pathway Response	mTOR signaling pathway			hsa04150
	Apoptosis			hsa04210
Cell Process	Cell apoptosis
In-vitro Model	AGS	Gastric adenocarcinoma	Homo sapiens	CVCL_0139
	HGC-27	Gastric carcinoma	Homo sapiens	CVCL_1279
Response Summary	Omeprazole pretreatment could enhance the inhibitory effect of 5-Fu, DDP and TAX on gastric cancer cells. FTO inhibition induced by omeprazole enhanced the activation of mTORC1 signal pathway that inhibited the prosurvival autophagy so as to improve the antitumor efficiency of chemotherapeutic drugs on GC cells. Meanwhile, transcript level of DNA damage-inducible transcript 3 protein (DDIT3), which is an apoptosis-related tumor suppressor gene downstream of mTORC1, was regulated by omeprazole-induced FTO silence through an m6A-dependent mechanism. m6A modification and its eraser FTO plays a role in the improvement of chemosensitivity mediated by proton pump inhibitor omeprazole.
Experiment 2 Reporting the m6A-centered Disease Response of This Target Gene				[19]
Responsed Disease	Gastric cancer [ICD-11: 2B72]
Responsed Drug	Fluorouracil		Approved	Drug Info
Target Regulation	Down regulation
Pathway Response	mTOR signaling pathway			hsa04150
	Apoptosis			hsa04210
Cell Process	Cell apoptosis
In-vitro Model	AGS	Gastric adenocarcinoma	Homo sapiens	CVCL_0139
	HGC-27	Gastric carcinoma	Homo sapiens	CVCL_1279
Response Summary	Omeprazole pretreatment could enhance the inhibitory effect of 5-Fu, DDP and TAX on gastric cancer cells. FTO inhibition induced by omeprazole enhanced the activation of mTORC1 signal pathway that inhibited the prosurvival autophagy so as to improve the antitumor efficiency of chemotherapeutic drugs on GC cells. Meanwhile, transcript level of DNA damage-inducible transcript 3 protein (DDIT3), which is an apoptosis-related tumor suppressor gene downstream of mTORC1, was regulated by omeprazole-induced FTO silence through an m6A-dependent mechanism. m6A modification and its eraser FTO plays a role in the improvement of chemosensitivity mediated by proton pump inhibitor omeprazole.
Experiment 3 Reporting the m6A-centered Disease Response of This Target Gene				[19]
Responsed Disease	Gastric cancer [ICD-11: 2B72]
Responsed Drug	Paclitaxel		Approved	Drug Info
Target Regulation	Down regulation
Pathway Response	mTOR signaling pathway			hsa04150
	Apoptosis			hsa04210
Cell Process	Cell apoptosis
In-vitro Model	AGS	Gastric adenocarcinoma	Homo sapiens	CVCL_0139
	HGC-27	Gastric carcinoma	Homo sapiens	CVCL_1279
Response Summary	Omeprazole pretreatment could enhance the inhibitory effect of 5-Fu, DDP and TAX on gastric cancer cells. FTO inhibition induced by omeprazole enhanced the activation of mTORC1 signal pathway that inhibited the prosurvival autophagy so as to improve the antitumor efficiency of chemotherapeutic drugs on GC cells. Meanwhile, transcript level of DNA damage-inducible transcript 3 protein (DDIT3), which is an apoptosis-related tumor suppressor gene downstream of mTORC1, was regulated by omeprazole-induced FTO silence through an m6A-dependent mechanism. m6A modification and its eraser FTO plays a role in the improvement of chemosensitivity mediated by proton pump inhibitor omeprazole.

Ephrin type-B receptor 2 (ERK/EPHB2)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by FTO*
Cell Line	NB4 cell line	Homo sapiens
Treatment: shFTO NB4 cells Control: shNS NB4 cells		GSE103494
Regulation		logFC: 1.37E+00 p-value: 3.20E-04
More Results	Click to View More RNA-seq Results

Acute myeloid leukaemia [ICD-11: 2A60]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[20]
Responsed Disease	Acute myeloid leukaemia [ICD-11: 2A60]
Target Regulation	Up regulation
Pathway Response	Apoptosis			hsa04210
Cell Process	Cell apoptosis
In-vitro Model	OCI-AML-3	Adult acute myeloid leukemia	Homo sapiens	CVCL_1844
In-vitro Model	OCI-AML-2	Adult acute myeloid leukemia	Homo sapiens	CVCL_1619
Response Summary	FTO depended on its m6A RNA demethylase activity to activate PDGFRB/Ephrin type-B receptor 2 (ERK/EPHB2) signaling axis. FTO-mediated m6A demethylation plays an oncogenic role in NPM1-mutated Acute myeloid leukemia(AML).

Frizzled-10 (FZD10)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by FTO*
Cell Line	Mouse hippocampus	Mus musculus
Treatment: FTO knockout mice hippocampus Control: Wild type hippocampus		GSE94098
Regulation		logFC: -6.03E-01 p-value: 7.74E-04
More Results	Click to View More RNA-seq Results

Malignant mixed epithelial mesenchymal tumour [ICD-11: 2B5D]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[21]
Responsed Disease	Malignant mixed epithelial mesenchymal tumour of ovary [ICD-11: 2B5D.0]
Responsed Drug	PARPi		Investigative	Drug Info
Target Regulation	Down regulation
Pathway Response	Wnt signaling pathway			hsa04310
In-vitro Model	UWB1.289	Ovarian carcinoma	Homo sapiens	CVCL_B079
In-vitro Model	PEO1	Ovarian cystadenocarcinoma	Homo sapiens	CVCL_2686
In-vivo Model	2 × 10⁷ PARP inhibitor resistant PEO1 cells were suspended in 200 uL PBS : Matrigel (1:1) unilaterally injected subcutaneously into the right dorsal flank of 6-8 week-old female immunocompromised non-obese diabetic/severe combined immunodeficiency (NOD/SCID) gamma (NSG) mice. When the average tumor size reached ~100 mm3, the mice were then randomized into four groups and treated with vehicle control, Olaparib (50 mg/kg), XAV939 (5 mg/kg) or a combination daily for 18 days.
Response Summary	Downregulation of m6A demethylases FTO and ALKBH5 was sufficient to increase Frizzled-10 (FZD10) mRNA m6A modification and reduce PARPi sensitivity, the finding elucidates a novel regulatory mechanism of PARPi resistance in EOC by showing that m6A modification of FZD10 mRNA contributes to PARPi resistance in BRCA-deficient EOC cells via upregulation of Wnt/Bete-catenin pathway.

G1/S-specific cyclin-D1 (CCND1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by FTO*
Cell Line	NB4 cell line	Homo sapiens
Treatment: FTO inhibition NB4 cells Control: NB4 cells		GSE103495
Regulation		logFC: -7.40E-01 p-value: 1.34E-03
More Results	Click to View More RNA-seq Results

Obesity [ICD-11: 5B81]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[15]
Responsed Disease	Obesity [ICD-11: 5B81]
Pathway Response	Cell cycle	hsa04110
Cell Process	Cell cycle
Response Summary	Metformin could inhibit adipogenesis and combat obesity, metformin could inhibit protein expression of FTO, leading to increased m6A methylation levels of G1/S-specific cyclin-D1 (CCND1) and Cdk2(two crucial regulators in cell cycle). Ccnd1 and Cdk2 with increased m6A levels were recognised by YTHDF2, causing an YTHDF2-dependent decay and decreased protein expressions.

Glutamate receptor ionotropic, NMDA 1 (NMDAR1/GRIN1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by FTO*
Cell Line	UMRC2 cell line	Homo sapiens
Treatment: FTO knockdown UMRC2 cells Control: Wild type UMRC2 cells		GSE139123
Regulation		logFC: -9.35E-01 p-value: 3.38E-05
More Results	Click to View More RNA-seq Results

Parkinson disease [ICD-11: 8A00]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[22]
Responsed Disease	Parkinson disease [ICD-11: 8A00]
Target Regulation	Up regulation
In-vitro Model	HEK293T	Normal	Homo sapiens	CVCL_0063
	PC-12	Lung papillary adenocarcinoma	Homo sapiens	CVCL_S979
	SH-SY5Y	Neuroblastoma	Homo sapiens	CVCL_0019
In-vivo Model	Two weeks after the stereotaxic surgery, all the animals were intraperitoneally injected with apomorphine at a dose of 0.5 mg/kg to induce the contralateral rotations. Ten minutes after the injection, a video was used to record the rotations of each rat for 20 min. Only those 6-OHDA induced rats showing robust contralateral turning (>7 turns/min) that were injected with 6-OHDA were used in subsequent experiments.
Response Summary	Decreased m6A in dopaminergic cells by overexpressing a nucleic acid demethylase, FTO, or by m6A inhibitor. m6A reduction could induce the expression of Glutamate receptor ionotropic, NMDA 1 (NMDAR1/GRIN1), and elevate oxidative stress and Ca2+ influx, resulting in dopaminergic neuron apoptosis. m6A modification plays a vital role in the death of dopaminergic neuron, which provides a novel view of mRNA methylation to understand the epigenetic regulation of Parkinson's disease.

Glycogen synthase kinase-3 beta (GSK3Beta/GSK3B)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by FTO*
Cell Line	B16-OVA cell line	Mus musculus
Treatment: shFTO B16-OVA cells Control: shNC B16-OVA cells		GSE154952
Regulation		logFC: 6.35E-01 p-value: 1.84E-09
More Results	Click to View More RNA-seq Results

Aortic aneurysm or dissection [ICD-11: BD50]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[23]
Responsed Disease	Aortic aneurysm or dissection [ICD-11: BD50]
Target Regulation	Up regulation
Pathway Response	Nucleotide excision repair	hsa03420
Cell Process	DNA repair
	Cell proliferation and migration
In-vitro Model	VSMC (Human aortic vascular smooth muscle cells)
Response Summary	FTO expression significantly contributes to the phenotype conversion of VSMCs and the aortic dissecting aneurysm by the demethylation function (m6A), thereby providing a novel therapeutic target. Knockdown of FTO suppresses the Glycogen synthase kinase-3 beta (GSK3Beta/GSK3B) levels and Klf5 expression regardless of AngII treatment.

Heat shock 70 kDa protein 1A (HSPA1A)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by FTO*
Cell Line	253J cell line	Homo sapiens
Treatment: siFTO 253J cells Control: 253J cells		GSE150239
Regulation		logFC: 1.83E+00 p-value: 7.08E-08
More Results	Click to View More RNA-seq Results

Low bone mass disorder [ICD-11: FB83]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[24]
Responsed Disease	Osteoporosis [ICD-11: FB83.1]
Target Regulation	Up regulation
In-vitro Model	1H8 [Mouse hybridoma against human BMSC]	Normal	Mus musculus	CVCL_A7TU
In-vivo Model	Fto^KO mice were backcrossed to WT C57BL/6 mice to remove Cre and bred to homozygosity. Results are reported for male mice on the same genetic background (C57BL6/J). For the diet-induced bone loss studies, mice were fed a 60% high-fat diet (D12492, Research Diets) from 6 wk of age to 24 wk. Genotyping strategies are available upon request. NBD (KKKKKKKKGGTALDWSWLQTE) with the Trp to Ala substitutions designed to render the peptide inactive underlined, was a gift from D.C.G. and dissolved in water before use. Next, 10 mg/kg NBD was intraperitoneally injected in 29-wk old Fto^{Oc KO} mice every other day for 9 d. One day after the last injection, bone was harvested for analysis of DNA damage.
Response Summary	loss of Fto also increased susceptibility of osteoblasts to genotoxic damage from metabolic stress induced by exposure to HF is also consistent with this model for FTO action. FTO functions intrinsically in osteoblasts through Heat shock 70 kDa protein 1A (HSPA1A)-NF-Kappa-B signaling to enhance the stability of mRNA of proteins that function to protect cells from genotoxic damage.

Heat shock factor protein 1 (HSF1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by FTO*
Cell Line	NB4 cell line	Homo sapiens
Treatment: shFTO NB4 cells Control: shNS NB4 cells		GSE103494
Regulation		logFC: -7.09E-01 p-value: 1.48E-02
More Results	Click to View More RNA-seq Results

Multiple myeloma [ICD-11: 2A83]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[25]
Responsed Disease	Multiple myeloma [ICD-11: 2A83.1]
Responsed Drug	Bortezomib		Approved	Drug Info
Target Regulation	Up regulation
In-vitro Model	RPMI-8226	Plasma cell myeloma	Homo sapiens	CVCL_0014
In-vitro Model	MM1.R	Plasma cell myeloma	Homo sapiens	CVCL_8794
In-vivo Model	A total of 3×10⁶ RPMI8226/MM1R-Luc cells were intravenously injected into NCG mice to establish a disseminated human MM xenograft model. The in vivo antitumor effect of the FTO inhibitor MA2 combined with or without the first-line chemotherapeutic agent BTZ was evaluated as follows: 3 days post xenotransplantation, MA2 (20 mg/kg), or vehicle control was injected intraperitoneally (i.p.) daily for 10 days, and BTZ was injected intraperitoneally on days 1, 4, 8, and 11. Mouse serum was collected at specified time points during the treatment, and the tumor burden was monitored by detecting myeloma cell-secreted Lambda light chains via a Human Lambda ELISA Kit (Bethyl Laboratories, No. E88-116). Tumor development was monitored weekly after treatment with an in vivo imaging system (IVIS, SI Imaging, Lago, and LagoX). Luciferin (150 mg/kg, YEASEN, Shanghai, China) was injected intraperitoneally into the mice.
Response Summary	FTO significantly promotes MM cell proliferation, migration, and invasion by targeting Heat shock factor protein 1 (HSF1)/HSPs in a YTHDF2-dependent manner. FTO inhibition, especially when combined with bortezomib (BTZ) treatment, synergistically inhibited myeloma bone tumor formation and extramedullary spread in NCG mice.

Heat shock protein HSP 90-alpha (HSP90/HSP90AA1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by FTO*
Cell Line	253J cell line	Homo sapiens
Treatment: siFTO 253J cells Control: 253J cells		GSE150239
Regulation		logFC: 7.64E-01 p-value: 2.38E-12
More Results	Click to View More RNA-seq Results

Brain cancer [ICD-11: 2A00]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[26]
Responsed Disease	Glioma [ICD-11: 2A00.0]
Target Regulation	Down regulation
Cell Process	Cell migration and proliferation
In-vitro Model	U251 (Fibroblasts or fibroblast like cells)
Response Summary	m6A regulated cell proliferation by influencing apoptosis of U251 cells through regulating Heat shock protein HSP 90-alpha (HSP90/HSP90AA1) expression.m6A level was decreased in glioma tissue, which was caused by decreased METTL3 and increased FTO levels.

Integrin alpha-6 (ITGA6)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by FTO*
Cell Line	253J cell line	Homo sapiens
Treatment: siFTO 253J cells Control: 253J cells		GSE150239
Regulation		logFC: 5.89E-01 p-value: 3.48E-07
More Results	Click to View More RNA-seq Results

Bladder cancer [ICD-11: 2C94]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[27]
Responsed Disease	Bladder cancer [ICD-11: 2C94]
Target Regulation	Up regulation
Pathway Response	Notch signaling pathway			hsa04330
Cell Process	Cell proliferation
	Cell invasion
	Cell apoptosis
In-vitro Model	HT-1197	Recurrent bladder carcinoma	Homo sapiens	CVCL_1291
	HT-1376	Bladder carcinoma	Homo sapiens	CVCL_1292
In-vivo Model	BALB/cnu/nu mice (4-5 weeks old) were used for the xenograft experiment. The mice were randomly divided into 2 groups (n = 6 for each group) and injected with 5 × 10⁶ HT-1197 cells in control group or FTO plasmid group, respectively.
Response Summary	In bladder cancer, the changes in m6A methylation level mainly appeared at 5' untranslated region (5' UTR) of MALAT1 and NOTCH1 transcripts, and at 3' UTR of CSNK2A2 and Integrin alpha-6 (ITGA6) transcripts, responding to the overexpression of FTO. SFPQ could influence the FTO-mediated m6A RNA demethylation, eventually affecting the gene expression.

Integrin beta-1 (ITGB1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by FTO*
Cell Line	253J cell line	Homo sapiens
Treatment: siFTO 253J cells Control: 253J cells		GSE150239
Regulation		logFC: 6.90E-01 p-value: 1.74E-07
More Results	Click to View More RNA-seq Results

Gastric cancer [ICD-11: 2B72]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[28]
Responsed Disease	Gastric cancer [ICD-11: 2B72]
Target Regulation	Up regulation
In-vitro Model	SNU-216	Gastric tubular adenocarcinoma	Homo sapiens	CVCL_3946
	MKN7	Gastric tubular adenocarcinoma	Homo sapiens	CVCL_1417
	MGC-803	Gastric mucinous adenocarcinoma	Homo sapiens	CVCL_5334
	HGC-27	Gastric carcinoma	Homo sapiens	CVCL_1279
	BGC-823	Gastric carcinoma	Homo sapiens	CVCL_3360
	AGS	Gastric adenocarcinoma	Homo sapiens	CVCL_0139
Response Summary	FTO was an independent risk factor for overall survival (OS) of GC patients and FTO could promote GC metastasis by upregulating the expression of Integrin beta-1 (ITGB1) via decreasing its m6A level.

Intercellular adhesion molecule 1 (ICAM1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by FTO*
Cell Line	NB4 cell line	Homo sapiens
Treatment: shFTO NB4 cells Control: shNS NB4 cells		GSE103494
Regulation		logFC: 1.83E+00 p-value: 2.17E-03
More Results	Click to View More RNA-seq Results

Diseases of the circulatory system [ICD-11: BE2Z]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[29]
Responsed Disease	Vascular diseases [ICD-11: BE2Z]
Responsed Drug	Atorvastatin		Approved	Drug Info
Target Regulation	Up regulation
In-vitro Model	THP-1	Childhood acute monocytic leukemia	Homo sapiens	CVCL_0006
	HUVEC-C	Normal	Homo sapiens	CVCL_2959
	HEK293T	Normal	Homo sapiens	CVCL_0063
Response Summary	FTO overexpression significantly upregulated the mRNA and protein levels of VCAM-1 and Intercellular adhesion molecule 1 (ICAM1), downregulated those of KLF2 and eNOS, and strongly attenuated the atorvastatin-mediated induction of KLF2 and eNOS expression. FTO could serve as a novel molecular target to modulate endothelial function in vascular diseases.

Krueppel-like factor 2 (KLF2)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by FTO*
Cell Line	B16F10 cell line	Mus musculus
Treatment: FTO knockout B16F10 cells Control: B16F10 cells		GSE134388
Regulation		logFC: -1.68E+00 p-value: 3.25E-02
More Results	Click to View More RNA-seq Results

Diseases of the circulatory system [ICD-11: BE2Z]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[29]
Responsed Disease	Vascular diseases [ICD-11: BE2Z]
Responsed Drug	Atorvastatin		Approved	Drug Info
Target Regulation	Down regulation
In-vitro Model	THP-1	Childhood acute monocytic leukemia	Homo sapiens	CVCL_0006
	HUVEC-C	Normal	Homo sapiens	CVCL_2959
	HEK293T	Normal	Homo sapiens	CVCL_0063
Response Summary	FTO overexpression significantly upregulated the mRNA and protein levels of VCAM-1 and ICAM-1, downregulated those of Krueppel-like factor 2 (KLF2) and eNOS, and strongly attenuated the atorvastatin-mediated induction of KLF2 and eNOS expression. FTO could serve as a novel molecular target to modulate endothelial function in vascular diseases.

Krueppel-like factor 5 (KLF5)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by FTO*
Cell Line	Cerebral cortex	Mus musculus
Treatment: METTL3 (f/f, Emx1-cre) cerebral cortex Control: Wild type cerebral cortex		GSE154992
Regulation		logFC: -1.34E+00 p-value: 1.46E-05
More Results	Click to View More RNA-seq Results

Aortic aneurysm or dissection [ICD-11: BD50]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[23]
Responsed Disease	Aortic aneurysm or dissection [ICD-11: BD50]
Target Regulation	Up regulation
Pathway Response	Nucleotide excision repair	hsa03420
Cell Process	DNA repair
	Cell proliferation and migration
In-vitro Model	VSMC (Human aortic vascular smooth muscle cells)
Response Summary	FTO expression significantly contributes to the phenotype conversion of VSMCs and the aortic dissecting aneurysm by the demethylation function (m6A), thereby providing a novel therapeutic target. Knockdown of FTO suppresses the p-GSK3-beta levels and Krueppel-like factor 5 (KLF5) expression regardless of AngII treatment.

Leukocyte immunoglobulin-like receptor subfamily B member 4 (LILRB4)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by FTO*
Cell Line	Mouse liver	Mus musculus
Treatment: FTO knockout mouse liver tissue Control: Wild type mouse liver tissue		GSE125785
Regulation		logFC: 1.12E+00 p-value: 2.09E-02
More Results	Click to View More RNA-seq Results

Acute myeloid leukaemia [ICD-11: 2A60]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[30]
Responsed Disease	Acute myeloid leukaemia [ICD-11: 2A60]
Target Regulation	Down regulation
Pathway Response	B cell receptor signaling pathway			hsa04662
Cell Process	Immune Evasion
In-vitro Model	MV4-11	Childhood acute monocytic leukemia	Homo sapiens	CVCL_0064
	THP-1	Childhood acute monocytic leukemia	Homo sapiens	CVCL_0006
	U-937	Adult acute monocytic leukemia	Homo sapiens	CVCL_0007
In-vivo Model	For each experiment, 6- to 8-week-old mice were used and randomly allocated to each group. For xenograft mouse, 0.1 × 10⁶ MA9.3ITD cells were transplanted into NRGS recipient mice intravenously. Drug treatment was started from 10 days after transplantation. CS2 was administered through intraperitoneal (i.p.) injection at 5mg/kg/day, every other day. CS1 dissolved in saturated Beta-cyclodextrin (C0926, Sigma-Aldrich) solution was delivered by intravenous injection (i.v.). Successful engraftment was observed following 4 weeks post inoculation displaying a level of about 5% human CD33+ cells in peripheral. To generate PDX mouse models, 1 × 10⁶ AML patient derived BMMNCs were transplanted into NRGS recipient mice intravenously, and drug treatment was started from 7 days later. CS2, FB23-2, and free CS1 were administered through i.p. injection at 5 mg/kg/day, while Micelle (900661, Sigma-Aldrich) packaged CS1 was delivered by i.v. injection at 5mg/kg/day. Both CS1 and CS2 were injected every other day for a total of ten times.
Response Summary	Genetic depletion and pharmacological inhibition of FTO dramatically attenuate leukemia stem/initiating cell self-renewal and reprogram immune response by suppressing expression of immune checkpoint genes, especially Leukocyte immunoglobulin-like receptor subfamily B member 4 (LILRB4). FTO inhibitors, such as rhein, meclofenamic acid (MA), MO-I-500, fluorescein, and R-2HG, can inhibit acute myeloid leukemia cell viability. CS1 and CS2 displayed a much higher efficacy in inhibiting AML cell viability.

Matrix metalloproteinase-24 (MMP24)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by FTO*
Cell Line	HEK293 cell line	Homo sapiens
Treatment: FTO knockdown HEK293T cells Control: HEK293T cells		GSE78040
Regulation		logFC: 8.43E-01 p-value: 7.94E-03
More Results	Click to View More RNA-seq Results

Pain disorders [ICD-11: 8E43]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[31]
Responsed Disease	Neuropathic Pain [ICD-11: 8E43.0]
Target Regulation	Up regulation
In-vivo Model	Mice were anesthetized with Nembutal. The lower back was dissected until the transverse lumbar process was exposed. After the process was removed, the underneath L4 spinal nerve was ligated with a silk 6-0 thread. A slight distal location was chosen for transection around the ligation site. Subsequent layers of muscle and skin were closed. The sham groups undertook identical procedures, but without the transection or ligature of the corresponding nerve. The intraspinal injection was performed as described previously. In short, after anesthetized with Nembutal, mice underwent hemilaminectomy at the L1-L2 vertebral segments. The intraspinal injection was carried out ipsilaterally on the left side. By using a glass micropipette, each animal received two injections (5 × 105 TU per injection, 0.8 mm from the midline, 0.5 mm apart in rostrocaudal axis, 0.5 mm deep) of lentivirus following the L3-L4 dorsal root entry zone after exposure of spinal cord. The tip of glass micropipette should reach a depth of lamina II-IV of the spinal cord. Finally, the dorsal muscle and skin were sutured layer by layer.
Response Summary	FTO was colocalized with Matrix metalloproteinase-24 (MMP24) in spinal neurons and shown increased binding to the Mmp24 mRNA in the spinal cord after SNL. SNL promoted the m6A eraser FTO binding to the Mmp24 mRNA, which subsequently facilitated the translation of MMP24 in the spinal cord, and ultimately contributed to neuropathic pain genesis.

Melanocortin receptor 4 (MC4R)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by FTO*
Cell Line	Cerebral cortex	Mus musculus
Treatment: METTL3 (f/f, Emx1-cre) cerebral cortex Control: Wild type cerebral cortex		GSE154992
Regulation		logFC: 7.52E-01 p-value: 2.88E-08
More Results	Click to View More RNA-seq Results

Prostate cancer [ICD-11: 2C82]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[32]
Responsed Disease	Prostate cancer [ICD-11: 2C82]
Target Regulation	Down regulation
Cell Process	Cell proliferation
	Cell migration
	Cell invasion
In-vitro Model	WPMY-1	Normal	Homo sapiens	CVCL_3814
	PC-3	Prostate carcinoma	Homo sapiens	CVCL_0035
	LNCaP	Prostate carcinoma	Homo sapiens	CVCL_0395
	DU145	Prostate carcinoma	Homo sapiens	CVCL_0105
	22Rv1	Prostate carcinoma	Homo sapiens	CVCL_1045
In-vivo Model	PCa cells carrying the transfected plasmid were subcutaneously injected into immunodeficient mice at a rate of 1 × 10⁶ cells per mouse according to a previous study. Tumor formation in the two groups of mice was observed and recorded by a designated personnel every day, and the volume of the tumors was measured. The nude mice were sacrificed 21 days after tumor formation, and the tumors were removed to measure their volume and weight.
Response Summary	FTO was downregulated in PCa and its expression level showed a relevance to the prognosis of PCa patients. Additionally, FTO could regulate the proliferation, migration and invasion of PCa via regulating the expression level of Melanocortin receptor 4 (MC4R).

Myc proto-oncogene protein (MYC)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by FTO*
Cell Line	NB4 cell line	Homo sapiens
Treatment: shFTO NB4 cells Control: shNS NB4 cells		GSE103494
Regulation		logFC: -6.81E-01 p-value: 3.45E-03
More Results	Click to View More RNA-seq Results

Brain cancer [ICD-11: 2A00]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[9]
Responsed Disease	Glioma [ICD-11: 2A00.0]
Responsed Drug	R-2HG		Investigative	Drug Info
Target Regulation	Down regulation
Cell Process	Glutamine metabolism
Cell Process	Cell apoptosis
In-vitro Model	8-MG-BA	Glioblastoma	Homo sapiens	CVCL_1052
	A-172	Glioblastoma	Homo sapiens	CVCL_0131
	DK-MG	Glioblastoma	Homo sapiens	CVCL_1173
	GaMG	Glioblastoma	Homo sapiens	CVCL_1226
	HEL	Erythroleukemia	Homo sapiens	CVCL_0001
	Jurkat	T acute lymphoblastic leukemia	Homo sapiens	CVCL_0065
	KOCL-45	B acute lymphoblastic leukemia	Homo sapiens	CVCL_3993
	KOCL-48	Childhood acute monocytic leukemia	Homo sapiens	CVCL_6867
	KOCL-50	B acute lymphoblastic leukemia	Homo sapiens	CVCL_6866
	KOCL-51	B acute lymphoblastic leukemia	Homo sapiens	CVCL_6865
	KOCL-69	B acute lymphoblastic leukemia	Homo sapiens	CVCL_3995
	KOPN-1	B acute lymphoblastic leukemia	Homo sapiens	CVCL_3937
	LN-18	Glioblastoma	Homo sapiens	CVCL_0392
	LN-229	Glioblastoma	Homo sapiens	CVCL_0393
	MA9.3 (MA9.3)
	MA9.6ITD (MLL-AF9 plus FLT3-ITD)
	MA9.6RAS (MLL-AF9 plus NRasG12D)
	MA9.6 (MLL-AF9)
	MA9.6ITD (MLL-AF9 plus FLT3-ITD)
	MA9.6RAS (MLL-AF9 plus NRasG12D)
	ME-1 [Human leukemia]	Adult acute myeloid leukemia	Homo sapiens	CVCL_2110
	ML-2	Adult acute myeloid leukemia	Homo sapiens	CVCL_1418
	MV4-11	Childhood acute monocytic leukemia	Homo sapiens	CVCL_0064
	NB4	Acute promyelocytic leukemia	Homo sapiens	CVCL_0005
	NOMO-1	Adult acute monocytic leukemia	Homo sapiens	CVCL_1609
	PL21	Familial adenomatous polyposis	Homo sapiens	CVCL_JM48
	T98G	Glioblastoma	Homo sapiens	CVCL_0556
	THP-1	Childhood acute monocytic leukemia	Homo sapiens	CVCL_0006
	U-87MG ATCC	Glioblastoma	Homo sapiens	CVCL_0022
	U-937	Adult acute monocytic leukemia	Homo sapiens	CVCL_0007
In-vivo Model	For R-2HG injection mouse models, sensitive (NOMO-1 and MA9.3ITD) or resistant (MA9.3RAS) cells were injected into NSGS or NRGS intravenously, and then R-2HG (6mg/kg body weight) or PBS were injected once daily through tail vein for 12 consecutive days starting from day 11 post xeno-transplantation.
Response Summary	This work demonstrates anti-tumor effects of 2HG in inhibiting proliferation/survival of FTO-high cancer cells via targeting FTO/m6A/Myc proto-oncogene protein (MYC)/CEBPA signaling.High levels of FTO sensitize leukemia cells to R-2HG, whereas hyperactivation of MYC signaling confers resistance that can be reversed by the inhibition of MYC signaling. R-2HG also displays anti-tumor activity in glioma. High levels of FTO sensitize leukemic cells to R-2HG, whereas hyperactivation of MYC signaling confers resistance that can be reversed by the inhibition of MYC signaling.

Solid tumour/cancer [ICD-11: 2A00-2F9Z]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[33]
Responsed Disease	Solid tumour/cancer [ICD-11: 2A00-2F9Z]
Target Regulation	Down regulation
Pathway Response	Wnt signaling pathway			hsa04310
	Central carbon metabolism in cancer			hsa05230
	Glycolysis / Gluconeogenesis			hsa00010
Cell Process	Glycolysis
In-vitro Model	NCI-H322	Minimally invasive lung adenocarcinoma	Homo sapiens	CVCL_1556
	HEK293T	Normal	Homo sapiens	CVCL_0063
In-vivo Model	Mice were randomized into several groups. For the subcutaneous implantation model, 1?×?10⁶ cells were injected subcutaneously into the flank regions of female BALB/c nude mice (4-5 weeks). For lung colonization assays, 1 × 10⁶ cells were injected into the tail vein of female NOD/SCID mice (6-7 weeks), and 6 weeks later the lung was removed and fixed with 10% formalin.
Response Summary	Wnt/Beta-catenin-mediated FTO downregulation and underscored the role of m6A modifications of Myc proto-oncogene protein (MYC) mRNA in regulating tumor cell glycolysis and growth.

Malignant haematopoietic neoplasm [ICD-11: 2B33]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[9]
Responsed Disease	Leukaemia [ICD-11: 2B33.4]
Responsed Drug	R-2HG		Investigative	Drug Info
Target Regulation	Down regulation
Cell Process	Glutamine metabolism
Cell Process	Cell apoptosis
In-vitro Model	8-MG-BA	Glioblastoma	Homo sapiens	CVCL_1052
	A-172	Glioblastoma	Homo sapiens	CVCL_0131
	DK-MG	Glioblastoma	Homo sapiens	CVCL_1173
	GaMG	Glioblastoma	Homo sapiens	CVCL_1226
	HEL	Erythroleukemia	Homo sapiens	CVCL_0001
	Jurkat	T acute lymphoblastic leukemia	Homo sapiens	CVCL_0065
	KOCL-45	B acute lymphoblastic leukemia	Homo sapiens	CVCL_3993
	KOCL-48	Childhood acute monocytic leukemia	Homo sapiens	CVCL_6867
	KOCL-50	B acute lymphoblastic leukemia	Homo sapiens	CVCL_6866
	KOCL-51	B acute lymphoblastic leukemia	Homo sapiens	CVCL_6865
	KOCL-69	B acute lymphoblastic leukemia	Homo sapiens	CVCL_3995
	KOPN-1	B acute lymphoblastic leukemia	Homo sapiens	CVCL_3937
	LN-18	Glioblastoma	Homo sapiens	CVCL_0392
	LN-229	Glioblastoma	Homo sapiens	CVCL_0393
	MA9.3 (MA9.3)
	MA9.6ITD (MLL-AF9 plus FLT3-ITD)
	MA9.6RAS (MLL-AF9 plus NRasG12D)
	MA9.6 (MLL-AF9)
	MA9.6ITD (MLL-AF9 plus FLT3-ITD)
	MA9.6RAS (MLL-AF9 plus NRasG12D)
	ME-1 [Human leukemia]	Adult acute myeloid leukemia	Homo sapiens	CVCL_2110
	ML-2	Adult acute myeloid leukemia	Homo sapiens	CVCL_1418
	MV4-11	Childhood acute monocytic leukemia	Homo sapiens	CVCL_0064
	NB4	Acute promyelocytic leukemia	Homo sapiens	CVCL_0005
	NOMO-1	Adult acute monocytic leukemia	Homo sapiens	CVCL_1609
	PL21	Familial adenomatous polyposis	Homo sapiens	CVCL_JM48
	T98G	Glioblastoma	Homo sapiens	CVCL_0556
	THP-1	Childhood acute monocytic leukemia	Homo sapiens	CVCL_0006
	U-87MG ATCC	Glioblastoma	Homo sapiens	CVCL_0022
	U-937	Adult acute monocytic leukemia	Homo sapiens	CVCL_0007
In-vivo Model	For R-2HG injection mouse models, sensitive (NOMO-1 and MA9.3ITD) or resistant (MA9.3RAS) cells were injected into NSGS or NRGS intravenously, and then R-2HG (6mg/kg body weight) or PBS were injected once daily through tail vein for 12 consecutive days starting from day 11 post xeno-transplantation.
Response Summary	This work demonstrates anti-tumor effects of 2HG in inhibiting proliferation/survival of FTO-high cancer cells via targeting FTO/m6A/Myc proto-oncogene protein (MYC)/CEBPA signaling.High levels of FTO sensitize leukemia cells to R-2HG, whereas hyperactivation of MYC signaling confers resistance that can be reversed by the inhibition of MYC signaling. R-2HG also displays anti-tumor activity in glioma. High levels of FTO sensitize leukemic cells to R-2HG, whereas hyperactivation of MYC signaling confers resistance that can be reversed by the inhibition of MYC signaling.

Colorectal cancer [ICD-11: 2B91]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[34]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulation	Up regulation
Cell Process	Cell proliferation
	Cell apoptosis
In-vitro Model	HCT 8	Colon adenocarcinoma	Homo sapiens	CVCL_2478
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
	SW620	Colon adenocarcinoma	Homo sapiens	CVCL_0547
In-vivo Model	RC cells SW480 at logarithmic growth phase were prepared into cell suspension with a concentration of about 1 × 10⁷/100 L, which was then injected into the left axilla of nude mice with a 1 ml syringe to establish a subcutaneous mouse xenograft model. Once the tumor volume reached about 50 mm³, the nude mice were injected with miR-96 antagomir or NC antagomir (10 nmol once every 5 days for 5 weeks). After 5 weeks, the mice were euthanized, after which the subcutaneous transplanted tumor was removed, and weighed.
Response Summary	miR-96 antagomir could potentially retard the cancerogenesis in colorectal cancer via AMPK-alpha-2-dependent inhibition of FTO and blocking FTO-mediated m6A modification of Myc proto-oncogene protein (MYC).

Pancreatic cancer [ICD-11: 2C10]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[36]
Responsed Disease	Pancreatic cancer [ICD-11: 2C10]
Target Regulation	Up regulation
Cell Process	Cell proliferation
In-vitro Model	BxPC-3	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0186
	HPDE	Normal	Homo sapiens	CVCL_4376
	PANC-1	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0480
	SW1990	Pancreatic adenocarcinoma	Homo sapiens	CVCL_1723
Response Summary	FTO has been indicated to interact with Myc proto-oncogene protein (MYC) proto-oncogene, bHLH transcription factor and to enhance its stability by decreasing its m6A level.the aforementioned observations indicate a novel mechanism for the regulation of pancreatic cancer cells by FTO

Lung cancer [ICD-11: 2C25]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[37]
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Pathway Response	p53 signaling pathway	hsa04115
	Central carbon metabolism in cancer	hsa05230
	PD-L1 expression and PD-1 checkpoint pathway in cancer	hsa05235
Response Summary	This study revealed that m6A methylation is closely related to the poor prognosis of non-small cell lung cancer patients via interference with the TIME, which suggests that m6A plays a role in optimizing individualized immunotherapy management and improving prognosis. The expression levels of METTL3, FTO and YTHDF1 in non-small cell lung cancer were changed. Patients in Cluster 1 had lower immunoscores, higher programmed death-ligand 1 (PD-L1) expression, and shorter overall survival compared to patients in Cluster 2. The Myc proto-oncogene protein (MYC) targets, E2 transcription Factor (E2F) targets were significantly enriched.

Cervical cancer [ICD-11: 2C77]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[38]
Responsed Disease	Cervical cancer [ICD-11: 2C77]
Target Regulation	Up regulation
Cell Process	Cell proliferation and migration
In-vitro Model	HeLa	Endocervical adenocarcinoma	Homo sapiens	CVCL_0030
In-vitro Model	SiHa	Cervical squamous cell carcinoma	Homo sapiens	CVCL_0032
Response Summary	FTO interacts with transcripts of E2F1 and Myc proto-oncogene protein (MYC), inhibition of FTO significantly impairs the translation efficiency of E2F1 and Myc.FTO plays important oncogenic role in regulating cervical cancer cells' proliferation.

Myeloid zinc finger 1 (MZF1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by FTO*
Cell Line	B16-OVA cell line	Mus musculus
Treatment: shFTO B16-OVA cells Control: shNC B16-OVA cells		GSE154952
Regulation		logFC: -6.18E-01 p-value: 2.06E-02
More Results	Click to View More RNA-seq Results

Colorectal cancer [ICD-11: 2B91]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[35]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulation	Down regulation
Pathway Response	Ubiquitin mediated proteolysis			hsa04120
Cell Process	Cell proliferation
In-vitro Model	SW620	Colon adenocarcinoma	Homo sapiens	CVCL_0547
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
	HCT 8	Colon adenocarcinoma	Homo sapiens	CVCL_2478
In-vivo Model	Twenty-four specific pathogen free female BALB/c nude mice (age: 6 weeks, weight: 15 ~ 18 g) were purchased from Slac Laboratory Animal Co., Ltd., and subcutaneously injected with SW620 cells stably transfected with oe-NC, oe-GSK3-Beta + oe-NC, or oe-GSK3-Beta + oe-c-Myc to establish a subcutaneous xenograft tumour model in nude mice.
Response Summary	GSK3beta inhibited Myeloid zinc finger 1 (MZF1) expression by mediating FTO-regulated m6A modification of MZF1 and then decreased the proto-oncogene c-Myc expression, thus hampering CRC cell proliferation.

Lung cancer [ICD-11: 2C25]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[39]
Responsed Disease	Lung squamous cell carcinoma [ICD-11: 2C25.2]
Target Regulation	Up regulation
Cell Process	mRNA stability
In-vitro Model	16HBE14o-	Normal	Homo sapiens	CVCL_0112
	BEAS-2B	Normal	Homo sapiens	CVCL_0168
	CHLH-1 (The human squamous lung cancer cell line)
	NCI-H226	Pleural epithelioid mesothelioma	Homo sapiens	CVCL_1544
	CHLH-1 (The human squamous lung cancer cell line)
	NCI-H520	Lung squamous cell carcinoma	Homo sapiens	CVCL_1566
Response Summary	FTO enhanced Myeloid zinc finger 1 (MZF1) expression by reducing m6A levels and mRNA stability in MZF1 mRNA transcript, leading to oncogenic functions. The functional importance of FTO in the tumor progression of LUSC and provides a potential therapeutic target for LUSC treatment.

Negative growth regulatory protein MyD118 (GADD45B)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by FTO*
Cell Line	HEK293 cell line	Homo sapiens
Treatment: FTO knockout HEK293 cells Control: Wild type HEK293 cells		GSE79577
Regulation		logFC: 8.04E-01 p-value: 5.27E-05
More Results	Click to View More RNA-seq Results

Muscular dystrophies [ICD-11: 8C70]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[40]
Responsed Disease	Muscular dystrophies [ICD-11: 8C70]
Target Regulation	Up regulation
Pathway Response	Nucleotide excision repair	hsa03420
	MAPK signaling pathway	hsa04010
Cell Process	DNA repair
In-vitro Model	GPM (Goat primary myoblasts)
In-vivo Model	Sixteen female goats in good body condition and suitable for pregnancy were selected. All selected goats underwent estrus synchronization treatment and were naturally mated. After 75 days of gestation, four male fetuses were removed from five pregnant goats during abortion operations, and their longissimus muscle samples were collected.
Response Summary	Negative growth regulatory protein MyD118 (GADD45B)-mediated m6A modification in Negative growth regulatory protein MyD118 (GADD45B) mRNA drives skeletal muscle differentiation by activating the p38 MAPK pathway, which provides a molecular mechanism for the regulation of myogenesis via RNA methylation.

Neurogenic locus notch homolog protein 1 (NOTCH1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by FTO*
Cell Line	253J cell line	Homo sapiens
Treatment: siFTO 253J cells Control: 253J cells		GSE150239
Regulation		logFC: 6.94E-01 p-value: 5.11E-07
More Results	Click to View More RNA-seq Results

Bladder cancer [ICD-11: 2C94]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[27]
Responsed Disease	Bladder cancer [ICD-11: 2C94]
Target Regulation	Down regulation
Pathway Response	Notch signaling pathway			hsa04330
Cell Process	Cell proliferation
	Cell invasion
	Cell apoptosis
In-vitro Model	HT-1197	Recurrent bladder carcinoma	Homo sapiens	CVCL_1291
	HT-1376	Bladder carcinoma	Homo sapiens	CVCL_1292
In-vivo Model	BALB/cnu/nu mice (4-5 weeks old) were used for the xenograft experiment. The mice were randomly divided into 2 groups (n = 6 for each group) and injected with 5 × 10⁶ HT-1197 cells in control group or FTO plasmid group, respectively.
Response Summary	In bladder cancer, the changes in m6A methylation level mainly appeared at 5' untranslated region (5' UTR) of MALAT1 and Neurogenic locus notch homolog protein 1 (NOTCH1) transcripts, and at 3' UTR of CSNK2A2 and ITGA6 transcripts, responding to the overexpression of FTO. SFPQ could influence the FTO-mediated m6A RNA demethylation, eventually affecting the gene expression.

Neutral amino acid transporter B(0) (SLC1A5)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by FTO*
Cell Line	253J cell line	Homo sapiens
Treatment: siFTO 253J cells Control: 253J cells		GSE150239
Regulation		logFC: -1.02E+00 p-value: 5.80E-30
More Results	Click to View More RNA-seq Results

Renal cell carcinoma [ICD-11: 2C90]

In total 1 item(s) under this disease			Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene			[41]
Responsed Disease	Renal cell carcinoma [ICD-11: 2C90]
Responsed Drug	GLS-IN-968	Investigative	Drug Info
Target Regulation	Up regulation
Pathway Response	Central carbon metabolism in cancer		hsa05230
	HIF-1 signaling pathway		hsa04066
	Central carbon metabolism in cancer		hsa05230
	Metabolic pathways		hsa01100
	VEGF signaling pathway		hsa04370
In-vitro Model	UMRC2-vec (CCRCC isogenic cell lines that are VHL-deficient)
Response Summary	Genetic inactivation of FTO using multiple orthogonal approaches revealed that FTO inhibition selectively reduces the growth and survival of VHL-deficient cells in vitro and in vivo. Integrated analysis of transcriptome-wide m6A-seq and mRNA-seq analysis identified the glutamine transporter Neutral amino acid transporter B(0) (SLC1A5) as an FTO target that promotes metabolic reprogramming and survival of VHL-deficient ccRCC cells. GLS1 inhibitors that target mitochondrial glutaminase and the conversion of glutamine to glutamate are currently being evaluated in early-phase clinical trials in ccRCC. These findings identify FTO as a potential HIF-independent therapeutic target for the treatment of VHL-deficient renal cell carcinoma.

Nucleophosmin (NPM1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by FTO*
Cell Line	NB4 cell line	Homo sapiens
Treatment: shFTO NB4 cells Control: shNS NB4 cells		GSE103494
Regulation		logFC: -7.88E-01 p-value: 1.66E-04
More Results	Click to View More RNA-seq Results

Acute myeloid leukaemia [ICD-11: 2A60]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[20]
Responsed Disease	Acute myeloid leukaemia [ICD-11: 2A60]
Target Regulation	Up regulation
In-vitro Model	OCI-AML-3	Adult acute myeloid leukemia	Homo sapiens	CVCL_1844
In-vitro Model	OCI-AML-2	Adult acute myeloid leukemia	Homo sapiens	CVCL_1619
Response Summary	FTO depended on its m6A RNA demethylase activity to activate PDGFRB/ERK signaling axis. FTO-mediated m6A demethylation plays an oncogenic role in Nucleophosmin (NPM1)-mutated Acute myeloid leukemia(AML).

P5C reductase 1 (PYCR1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by FTO*
Cell Line	253J cell line	Homo sapiens
Treatment: siFTO 253J cells Control: 253J cells		GSE150239
Regulation		logFC: -8.46E-01 p-value: 2.98E-19
More Results	Click to View More RNA-seq Results

Bladder cancer [ICD-11: 2C94]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[42]
Responsed Disease	Bladder cancer [ICD-11: 2C94]
Target Regulation	Up regulation
Pathway Response	mRNA surveillance pathway			hsa03015
Pathway Response	RNA degradation			hsa03018
Cell Process	RNA stability
In-vitro Model	T24	Bladder carcinoma	Homo sapiens	CVCL_0554
	SV-HUC-1	Normal	Homo sapiens	CVCL_3798
	RT-4	Bladder carcinoma	Homo sapiens	CVCL_0036
	J82	Bladder carcinoma	Homo sapiens	CVCL_0359
	EJ (Human bladder cancer cells)
	5637	Bladder carcinoma	Homo sapiens	CVCL_0126
In-vivo Model	T24 cells were subcutaneously injected into the mice (1 x 10⁶ cells / injecting site).
Response Summary	FTO decreased N6-methyladenosine methylation level in P5C reductase 1 (PYCR1) through its demethylase enzymatic activity and stabilized PYCR1 transcript to promote bladder cancer initiation and progression.

PDH kinase 1 (PDK1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by FTO*
Cell Line	NB4 cell line	Homo sapiens
Treatment: shFTO NB4 cells Control: shNS NB4 cells		GSE103494
Regulation		logFC: -7.19E-01 p-value: 8.18E-03
More Results	Click to View More RNA-seq Results

Brain cancer [ICD-11: 2A00]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[43]
Responsed Disease	Glioblastoma [ICD-11: 2A00.00]
Responsed Drug	Temozolomide		Approved	Drug Info
Target Regulation	Up regulation
Pathway Response	Citrate cycle			hsa00020
	Central carbon metabolism in cancer			hsa05230
Cell Process	Aerobic glycolysis
	Cell apoptosis
In-vitro Model	LN-18	Glioblastoma	Homo sapiens	CVCL_0392
	LN-229	Glioblastoma	Homo sapiens	CVCL_0393
	SHG-44	Astrocytoma	Homo sapiens	CVCL_6728
	U251 (Fibroblasts or fibroblast like cells)
	U87 (A primary glioblastoma cell line)
Response Summary	Long noncoding RNA just proximal to X-inactive specific transcript facilitates aerobic glycolysis and temozolomide chemoresistance by promoting stability of PDH kinase 1 (PDK1) mRNA in an m6A-dependent manner in glioblastoma multiforme cells. JPX interacted with N6-methyladenosine (m6A) demethylase FTO alpha-ketoglutarate dependent dioxygenase (FTO) and enhanced FTO-mediated PDK1 mRNA demethylation.

Peroxisome proliferator-activated receptor gamma (PPARG)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by FTO*
Cell Line	NB4 cell line	Homo sapiens
Treatment: shFTO NB4 cells Control: shNS NB4 cells		GSE103494
Regulation		logFC: 2.20E+00 p-value: 2.69E-03
More Results	Click to View More RNA-seq Results

Low bone mass disorder [ICD-11: FB83]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[44]
Responsed Disease	Osteoporosis [ICD-11: FB83.1]
Target Regulation	Down regulation
Pathway Response	Osteoclast differentiation	hsa04380
In-vitro Model	hMSCs (Human osteogenesis of mesenchymal stem cells (HUXMA-01001, Cyagen Biosciences, Suzhou, China))
In-vivo Model	Conditional knockout of Fto in bone in mice was generated as previously described. Throughout the study, mice were maintained on a 12 h: 12 h light:dark cycle in a specific pathogen-free facility.
Response Summary	Both depletion of FTO and application of the FTO inhibitor FB23 or FB23-2 impaired osteogenic differentiation of human MSCs. Knockdown of Peroxisome proliferator-activated receptor gamma (PPARG) promoted FTO-induced expression of the osteoblast biomarkers ALPL and OPN during osteogenic differentiation. This study demonstrates the functional significance of the FTO-PPARG axis in promoting the osteogenesis of human MSCs and sheds light on the role of m6A modification in mediating osteoporosis and osteonecrosis.

Platelet-derived growth factor C (PDGFC)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by FTO*
Cell Line	253J cell line	Homo sapiens
Treatment: siFTO 253J cells Control: 253J cells		GSE150239
Regulation		logFC: 8.37E+00 p-value: 3.21E-02
More Results	Click to View More RNA-seq Results

Pancreatic cancer [ICD-11: 2C10]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[45]
Responsed Disease	Pancreatic cancer [ICD-11: 2C10]
Target Regulation	Up regulation
Pathway Response	PI3K-Akt signaling pathway			hsa04151
In-vitro Model	SW1990	Pancreatic adenocarcinoma	Homo sapiens	CVCL_1723
	PANC-1	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0480
	MIA PaCa-2	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0428
	HPDE	Normal	Homo sapiens	CVCL_4376
	CFPAC-1	Cystic fibrosis	Homo sapiens	CVCL_1119
	Capan-1	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0237
	BxPC-3	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0186
	AsPC-1	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0152
	HEK293T	Normal	Homo sapiens	CVCL_0063
In-vivo Model	The right flanks of mice were injected subcutaneously with 2 × 10⁶ MiaPaCa-2 cells stably expressing shFTO and a scrambled shRNA in 100 uL PBS. Tumors were measured using an external caliper once per week, and tumor volume was calculated with the formula: (length × width2)/2.
Response Summary	FTO downregulation leads to increased m6A modifications in the 3' UTR of Platelet-derived growth factor C (PDGFC) and then modulates the degradation of its transcriptional level in an m6A-YTHDF2-dependent manner, highlighting a potential therapeutic target for PDAC treatment and prognostic prediction.

Platelet-derived growth factor receptor beta (PDGFRB)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by FTO*
Cell Line	NB4 cell line	Homo sapiens
Treatment: shFTO NB4 cells Control: shNS NB4 cells		GSE103494
Regulation		logFC: 6.89E-01 p-value: 9.80E-03
More Results	Click to View More RNA-seq Results

Acute myeloid leukaemia [ICD-11: 2A60]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[20]
Responsed Disease	Acute myeloid leukaemia [ICD-11: 2A60]
Target Regulation	Up regulation
Cell Process	Cell apoptosis
In-vitro Model	OCI-AML-3	Adult acute myeloid leukemia	Homo sapiens	CVCL_1844
In-vitro Model	OCI-AML-2	Adult acute myeloid leukemia	Homo sapiens	CVCL_1619
Response Summary	FTO depended on its m6A RNA demethylase activity to activate Platelet-derived growth factor receptor beta (PDGFRB)/ERK signaling axis. FTO-mediated m6A demethylation plays an oncogenic role in NPM1-mutated Acute myeloid leukemia(AML).

PPAR-gamma coactivator 1-alpha (PGC-1a/PPARGC1A)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by FTO*
Cell Line	253J cell line	Homo sapiens
Treatment: siFTO 253J cells Control: 253J cells		GSE150239
Regulation		logFC: 4.58E+00 p-value: 7.10E-03
More Results	Click to View More RNA-seq Results

Renal cell carcinoma [ICD-11: 2C90]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[46]
Responsed Disease	Renal cell carcinoma of kidney [ICD-11: 2C90.0]
Target Regulation	Up regulation
Cell Process	Oxidative stress
	ROS production
In-vitro Model	HEK293T	Normal	Homo sapiens	CVCL_0063
	769-P	Renal cell carcinoma	Homo sapiens	CVCL_1050
	786-O	Renal cell carcinoma	Homo sapiens	CVCL_1051
In-vivo Model	Five- to 6-week-old male athymic nude mice purchased by Charles River were used for the xenograft model. 769-P cells stably expressing Ctrl, FTO and FTO-mut were trypsinized and washed twice to thrice with standardized PBS, and then, 5 × 10⁶ cells in 100 uL of PBS was subcutaneously injected into the flanks of the mice (five mice per group). Mice were monitored twice every week for tumour growth, and tumour diameters were measured using a caliper.
Response Summary	FTO plays a critical anti-tumorigenic role in Clear Cell Renal Cell Carcinoma.Restored expression of FTO, through reducing m6A levels in mRNA transcripts of its critical target gene PPAR-gamma coactivator 1-alpha (PGC-1a/PPARGC1A), increases mitochondrial content, ROS production and oxidative damage, with the most important effect of repressed tumour growth.

Muscular dystrophies [ICD-11: 8C70]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[47]
Responsed Disease	Muscular dystrophies [ICD-11: 8C70]
Target Regulation	Up regulation
Cell Process	Myogenic differentiation
	mTOR signaling pathway (hsa04150)
In-vitro Model	MPM (Mouse primary myoblasts from about 10-day-old C57BL/6J were isolated)
	C2C12	Normal	Mus musculus	CVCL_0188
	HEK293-FT	Normal	Homo sapiens	CVCL_6911
In-vivo Model	To generate doxycycline-inducible skeletal muscle-specific FTO deletion mice, FTO^flox/flox mice were crossed with HSA-Cre mice to generate FTO^flox/+ HSA-Cre mice, which were then crossed to FTO^flox/flox mice to generate FTO^flox/flox and FTO^flox/flox HSA-Cre mice.
Response Summary	FTO downregulation suppressed mitochondria biogenesis and energy production, showing as the decreased mitochondria mass and mitochondrial DNA (mtDNA) content, the downregulated expression of mtDNA-encoding genes and PPAR-gamma coactivator 1-alpha (PGC-1a/PPARGC1A) gene, together with declined ATP level. These findings provide the first evidence for the contribution of FTO for skeletal muscle differentiation.

Programmed cell death 1 ligand 1 (CD274/PD-L1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by FTO*
Cell Line	253J cell line	Homo sapiens
Treatment: siFTO 253J cells Control: 253J cells		GSE150239
Regulation		logFC: 3.22E+00 p-value: 3.45E-05
More Results	Click to View More RNA-seq Results

Head and neck squamous carcinoma [ICD-11: 2B6E]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[48]
Responsed Disease	Oral squamous cell carcinoma [ICD-11: 2B6E.0]
Target Regulation	Up regulation
Pathway Response	PD-L1 expression and PD-1 checkpoint pathway in cancer	hsa05235
Response Summary	Arecoline-induced FTO promotes the stability and expression levels of Programmed cell death 1 ligand 1 (CD274/PD-L1) transcripts through mediating m6A modification and MYC activity, respectively. PD-L1 upregulation confers superior cell proliferation, migration, and resistance to T-cell killing to OSCC cells.

Lung cancer [ICD-11: 2C25]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[37]
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Pathway Response	p53 signaling pathway	hsa04115
	Central carbon metabolism in cancer	hsa05230
	PD-L1 expression and PD-1 checkpoint pathway in cancer	hsa05235
Response Summary	This study revealed that m6A methylation is closely related to the poor prognosis of non-small cell lung cancer patients via interference with the TIME, which suggests that m6A plays a role in optimizing individualized immunotherapy management and improving prognosis. The expression levels of METTL3, FTO and YTHDF1 in non-small cell lung cancer were changed. Patients in Cluster 1 had lower immunoscores, higher Programmed cell death 1 ligand 1 (CD274/PD-L1) expression, and shorter overall survival compared to patients in Cluster 2. The hallmarks of the Myelocytomatosis viral oncogene (MYC) targets, E2 transcription Factor (E2F) targets were significantly enriched.

Pyruvate kinase PKM (PKM2/PKM)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by FTO*
Cell Line	NB4 cell line	Homo sapiens
Treatment: shFTO NB4 cells Control: shNS NB4 cells		GSE103494
Regulation		logFC: 1.52E+00 p-value: 5.79E-04
More Results	Click to View More RNA-seq Results

Liver cancer [ICD-11: 2C12]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[49]
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
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.
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.

Ras GTPase-activating-like protein IQGAP1 (IQGAP1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by FTO*
Cell Line	NB4 cell line	Homo sapiens
Treatment: shFTO NB4 cells Control: shNS NB4 cells		GSE103494
Regulation		logFC: 6.41E-01 p-value: 2.42E-02
More Results	Click to View More RNA-seq Results

Liver cancer [ICD-11: 2C12]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[50]
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
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
In-vitro Model	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).
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.

Runt-related transcription factor 2 (Runx2)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by FTO*
Cell Line	Cerebral cortex	Mus musculus
Treatment: METTL3 (f/f, Emx1-cre) cerebral cortex Control: Wild type cerebral cortex		GSE154992
Regulation		logFC: -1.60E+00 p-value: 6.61E-03
More Results	Click to View More RNA-seq Results

Low bone mass disorder [ICD-11: FB83]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[51]
Responsed Disease	Osteoporosis [ICD-11: FB83.1]
Target Regulation	Down regulation
In-vitro Model	BMSCs (BMSCs were obtained from the femurs and tibias of 2-3-week-old Sprague-Dawley male rats (Animal Center of Sun Yat-sen University))
In-vivo Model	Female C57BL/6J mice (14 weeks old) were treated with bilateral ovariectomy under general anesthesia. Eight weeks after surgery, tibial plateau was harvested and the structure were evaluated with a SCANCO Medical uCT 40 scanner.
Response Summary	RNA N6-methyladenosine demethylase FTO promotes osteoporosis through demethylating Runt-related transcription factor 2 (Runx2) mRNA and inhibiting osteogenic differentiation.

Sarcoplasmic/endoplasmic reticulum calcium ATPase 2 (SERCA2a/ATP2A2)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by FTO*
Cell Line	NB4 cell line	Homo sapiens
Treatment: shFTO NB4 cells Control: shNS NB4 cells		GSE103494
Regulation		logFC: 5.91E-01 p-value: 1.58E-02
More Results	Click to View More RNA-seq Results

Energy metabolism disorder [ICD-11: 5C53]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[52]
Responsed Disease	Energy metabolism disorder [ICD-11: 5C53]
Target Regulation	Up regulation
Cell Process	Energy metabolism
	Cell apoptosis
In-vitro Model	AC16 [Human hybrid cardiomyocyte]	Normal	Homo sapiens	CVCL_4U18
Response Summary	FTO modification of N6 -methyladenosine is associated with myocardial cell energy metabolism disorder. FTO reduced the m6A level of Sarcoplasmic/endoplasmic reticulum calcium ATPase 2 (SERCA2a/ATP2A2) mRNA through demethylation, thus promoting SERCA2a expression, maintaining calcium homeostasis, and improving energy metabolism of H/R cardiomyocytes.

Sequestosome-1 (SQSTM1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by FTO*
Cell Line	253J cell line	Homo sapiens
Treatment: siFTO 253J cells Control: 253J cells		GSE150239
Regulation		logFC: 6.53E-01 p-value: 1.38E-07
More Results	Click to View More RNA-seq Results

Solid tumour/cancer [ICD-11: 2A00-2F9Z]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[53]
Responsed Disease	Solid tumour/cancer [ICD-11: 2A00-2F9Z]
Target Regulation	Down regulation
Pathway Response	Autophagy			hsa04140
Cell Process	Cellular Processes, Transport and catabolism
	Cell autophagy
In-vitro Model	HaCaT	Normal	Homo sapiens	CVCL_0038
	HEK293T	Normal	Homo sapiens	CVCL_0063
	HeLa	Endocervical adenocarcinoma	Homo sapiens	CVCL_0030
	MEF (Mouse embryonic fibroblasts)
In-vivo Model	As cells (5 million) in Matrigel or As-T (1 million) cells in PBS with or without gene manipulations were injected subcutaneously into the right flanks of female mice (6-8 weeks of age). For treatment with CS1 or CS2, As-T cells (1 million) in PBS were injected subcutaneously into the right flanks of 6-week-old female nude mice.
Response Summary	FTO deletion inhibited arsenic-induced tumorigenesis. Epidermis-specific FTO deletion prevented skin tumorigenesis induced by arsenic and UVB irradiation. NEDD4L was identified as the m6A-modified gene target of FTO. Arsenic stabilizes FTO protein through inhibiting Sequestosome-1 (SQSTM1)-mediated selective autophagy. FTO-mediated dysregulation of mRNA m6A methylation as an epitranscriptomic mechanism to promote arsenic tumorigenicity. Arsenic suppresses p62 expression by downregulating the NF-Kappa-B pathway to upregulate FTO.

Human skin lesions [ICD-11: ME60]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[53]
Responsed Disease	Human skin lesions [ICD-11: ME60]
Target Regulation	Down regulation
Pathway Response	Autophagy			hsa04140
Cell Process	Cellular Processes, Transport and catabolism
	Cell autophagy
In-vitro Model	HaCaT	Normal	Homo sapiens	CVCL_0038
	HEK293T	Normal	Homo sapiens	CVCL_0063
	HeLa	Endocervical adenocarcinoma	Homo sapiens	CVCL_0030
	MEF (Mouse embryonic fibroblasts)
In-vivo Model	As cells (5 million) in Matrigel or As-T (1 million) cells in PBS with or without gene manipulations were injected subcutaneously into the right flanks of female mice (6-8 weeks of age). For treatment with CS1 or CS2, As-T cells (1 million) in PBS were injected subcutaneously into the right flanks of 6-week-old female nude mice.
Response Summary	FTO deletion inhibited arsenic-induced tumorigenesis. Epidermis-specific FTO deletion prevented skin tumorigenesis induced by arsenic and UVB irradiation. NEDD4L was identified as the m6A-modified gene target of FTO. Arsenic stabilizes FTO protein through inhibiting Sequestosome-1 (SQSTM1)-mediated selective autophagy. FTO-mediated dysregulation of mRNA m6A methylation as an epitranscriptomic mechanism to promote arsenic tumorigenicity. Arsenic suppresses p62 expression by downregulating the NF-Kappa-B pathway to upregulate FTO.

Serine/threonine-protein kinase ULK1 (ULK1/ATG1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by FTO*
Cell Line	253J cell line	Homo sapiens
Treatment: siFTO 253J cells Control: 253J cells		GSE150239
Regulation		logFC: -6.13E-01 p-value: 1.25E-06
More Results	Click to View More RNA-seq Results

Gastric cancer [ICD-11: 2B72]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[54]
Responsed Disease	Gastric cancer [ICD-11: 2B72]
Responsed Drug	Cisplatin		Approved	Drug Info
Target Regulation	Up regulation
In-vitro Model	GES-1	Normal	Homo sapiens	CVCL_EQ22
In-vitro Model	SGC-7901	Gastric carcinoma	Homo sapiens	CVCL_0520
In-vivo Model	A total of 5 × 10⁶ cells in 200 ul PBS were injected subcutaneously into the flanks of nude mice. After injection, cisplatin treatment was initiated on day 5. Mice were injected with 5 mg/kg cisplatin or PBS solution in the abdominal cavity once a week for 3?weeks.
Response Summary	Knockdown of FTO reversed cisplatin resistance of SGC-7901/DDP cells both in vitro and in vivo, which was attributed to the inhibition of Serine/threonine-protein kinase ULK1 (ULK1)-mediated autophagy. These findings indicate that the FTO/ULK1 axis exerts crucial roles in cisplatin resistance of gastric cancer.

Sterol regulatory element-binding protein 1 (SREBF1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by FTO*
Cell Line	253J cell line	Homo sapiens
Treatment: siFTO 253J cells Control: 253J cells		GSE150239
Regulation		logFC: -1.19E+00 p-value: 4.36E-38
More Results	Click to View More RNA-seq Results

Non-alcoholic fatty liver disease [ICD-11: DB92]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[10]
Responsed Disease	Non-alcoholic fatty liver disease [ICD-11: DB92]
Target Regulation	Up regulation
Cell Process	Lipogenesis
In-vitro Model	HEK293T	Normal	Homo sapiens	CVCL_0063
In-vitro Model	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
In-vivo Model	After being fed with high-fat diet for 4 weeks, mice were given twice vena caudalis injection of control siRNA or Cidec siRNA (50 ug/mouse) mixed with liposome. Liposomes were prepared as described elsewhere.
Response Summary	FTO increased the lipid accumulation in hepatocytes by increasing nuclear translocation of Sterol regulatory element-binding protein 1 (SREBF1) and SREBP1c maturation, thus improving the transcriptional activity of LD-associated protein CIDEC.The studies provide new mechanistic insight into nonalcoholic fatty liver disease (NAFLD) mediated by FTO.

Superoxide dismutase [Mn], mitochondrial (SOD2)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by FTO*
Cell Line	NB4 cell line	Homo sapiens
Treatment: shFTO NB4 cells Control: shNS NB4 cells		GSE103494
Regulation		logFC: 8.09E-01 p-value: 6.85E-03
More Results	Click to View More RNA-seq Results

Multiple myeloma [ICD-11: 2A83]

In total 1 item(s) under this disease			Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene			[55]
Responsed Disease	Multiple myeloma [ICD-11: 2A83.1]
Responsed Drug	Bortezomib	Approved	Drug Info
Target Regulation	Down regulation
Response Summary	FTO promotes Bortezomib resistance via m6A-dependent destabilization of Superoxide dismutase [Mn], mitochondrial (SOD2) expression in multiple myeloma.

Tissue factor pathway inhibitor 2 (TFPI-2)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by FTO*
Cell Line	253J cell line	Homo sapiens
Treatment: siFTO 253J cells Control: 253J cells		GSE150239
Regulation		logFC: 1.23E+01 p-value: 1.69E-03
More Results	Click to View More RNA-seq Results

Pancreatic cancer [ICD-11: 2C10]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[56]
Responsed Disease	Pancreatic cancer [ICD-11: 2C10]
Target Regulation	Down regulation
Cell Process	Cell growth
	cell migration
	cell invasion
Response Summary	Knockdown of FTO increases m6A methylation of Tissue factor pathway inhibitor 2 (TFPI-2) mRNA in PC cells, thereby increasing mRNA stability via the m6A reader YTHDF1.

Transcription factor PU.1 (SPI1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by FTO*
Cell Line	TPC_1 cell line	Homo sapiens
Treatment: FTO overexpression TPC_1 cells Control: TPC_1 cells		GSE199206
Regulation		logFC: -7.40E+00 p-value: 4.06E-02
More Results	Click to View More RNA-seq Results

Brain cancer [ICD-11: 2A00]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[57]
Responsed Disease	Glioblastoma [ICD-11: 2A00.00]
Target Regulation	Down regulation
In-vitro Model	U-87MG ATCC	Glioblastoma	Homo sapiens	CVCL_0022
	U251 (Fibroblasts or fibroblast like cells)
	U-118MG	Astrocytoma	Homo sapiens	CVCL_0633
	LN-229	Glioblastoma	Homo sapiens	CVCL_0393
	A-172	Glioblastoma	Homo sapiens	CVCL_0131
In-vivo Model	BALB/c male nude mice were 4 weeks old. GBM cells with stable overexpression or knockdown of FTO and ovNC or shNC were transduced with lentivirus expressing luciferase. The cells were intracranially injected at a density of 5 × 10⁵/10 uL into every mouse to form an orthotopic xenograft model. Coordinates of injection were 1 mm anterior and 2.5 mm right to the bregma, at a depth of 3.5 mm (the right frontal lobes of the mouse). Every 6 days, bioluminescence imaging (IVIS Lumina Series III; PerkinElmer, Waltham, MA) was used to image the mouse. At 8 days, we randomly chose 5 mice from each group to euthanize them, and their brain tissues were fixed with paraformaldehyde for further study. Another 5 mice were used for survival time analysis. For DB2313 (563801; MedKoo) anti-tumor research, male nude mice were subcutaneously injected with 5 × 10⁶ U87MG cells suspended in 0.1 mL PBS. After 7 days, mice were intraperitoneally injected with DB2313 at density of 10 mg/kg/day dissolved in PBS solvent containing 10% DMSO for 7 days. The other group treated with vehicle only was set as the control group.
Response Summary	FTO inhibited growth, migration and invasion of GBM cells in vitro and in vivo.decreased FTO expression could induce the downregulation of MTMR3 expression by modulating the processing of pri-miR-10a in an m6A/HNRNPA2B1-dependent manner in GBM cells. Furthermore, the transcriptional activity of FTO was inhibited by the transcription factor Transcription factor PU.1 (SPI1).

Transcription factor SOX-10 (SOX10)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by FTO*
Cell Line	Cerebral cortex	Mus musculus
Treatment: METTL3 (f/f, Emx1-cre) cerebral cortex Control: Wild type cerebral cortex		GSE154992
Regulation		logFC: -8.13E-01 p-value: 2.61E-03
More Results	Click to View More RNA-seq Results

Melanoma [ICD-11: 2C30]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[7]
Responsed Disease	Melanoma [ICD-11: 2C30]
Responsed Drug	PMID31239444-anti-PD1 antibody		Investigative	Drug Info
Target Regulation	Up regulation
Pathway Response	PD-L1 expression and PD-1 checkpoint pathway in cancer			hsa05235
Cell Process	mRNA decay
In-vitro Model	B16-F10	Mouse melanoma	Mus musculus	CVCL_0159
	CHL-1	Melanoma	Homo sapiens	CVCL_1122
	624-mel	Melanoma	Homo sapiens	CVCL_8054
	NHEM (Normal Human Epidermal Melanocytes)
	SK-MEL-30	Cutaneous melanoma	Homo sapiens	CVCL_0039
	WM115	Melanoma	Homo sapiens	CVCL_0040
	WM35	Melanoma	Homo sapiens	CVCL_0580
	WM3670	Melanoma	Homo sapiens	CVCL_6799
	WM793	Melanoma	Homo sapiens	CVCL_8787
In-vivo Model	When the tumors reached a volume of 80-100 mm³, mice were treated with anti-PD-1 or isotype control antibody (200 ug/mouse) by i.p. injection, every other day for three times. For IFNγ blockade treatment, C57BL/6 mice were treated with anti-IFNγ antibody or isotype control IgG (250 ug/mouse) every other day after tumor cell inoculation.
Response Summary	These findings demonstrate a crucial role of FTO as an m6A demethylase in promoting melanoma tumorigenesis and anti-PD-1 resistance, and suggest that the combination of FTO inhibition with anti-PD-1 blockade reduces the resistance to immunotherapy in melanoma. Knockdown of FTO increases m6A methylation in the critical protumorigenic melanoma cell-intrinsic genes including PD-1 (PDCD1), CXCR4, and Transcription factor SOX-10 (SOX10), leading to increased RNA decay through the m6A reader YTHDF2.

Transcriptional coactivator YAP1 (YAP1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by FTO*
Cell Line	Cerebral cortex	Mus musculus
Treatment: METTL3 (f/f, Emx1-cre) cerebral cortex Control: Wild type cerebral cortex		GSE154992
Regulation		logFC: 6.87E-01 p-value: 5.76E-08
More Results	Click to View More RNA-seq Results

Head and neck squamous carcinoma [ICD-11: 2B6E]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[58]
Responsed Disease	Oral squamous cell carcinoma [ICD-11: 2B6E.0]
Target Regulation	Up regulation
Response Summary	Stable knockdown of FTO inhibited OSCC cell viability, colony formation, and tumor growth. Further, FTO depletion increased Transcriptional coactivator YAP1 (YAP1) m6A modification at mRNA 3'-untranslated region, accelerating the degradation of YAP1 mRNA, a well-documented oncogene promoting OSCC progression.

Ischemic heart disease [ICD-11: BA40-BA6Z]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[59]
Responsed Disease	Ischemic heart disease [ICD-11: BA40-BA6Z]
Target Regulation	Up regulation
Cell Process	Cell apoptosis
In-vitro Model	Neonatal rat ventricular cardiomyocytes (Primary myocyte cells)
In-vivo Model	After anesthesia (50 mg/kg pentobarbital sodium, intraperitoneal injection), the left thorax was cut to expose the heart, and the left anterior descending (LAD) coronary artery was ligated by 7/0 sterile suture. Myocardial ischemia was induced by 30 min of LAD coronary artery ligation and following 2 h of reperfusion. Sham group mice underwent the same surgical procedure without LAD coronary artery ligation.
Response Summary	FTO down-expressed in myocardial IRI mice and hypoxia/reoxygenation (H/R)-induced cardiomyocytes. Moreover, FTO uninstalled the methylation of Transcriptional coactivator YAP1 (YAP1) mRNA, and enforced the stability of Yap1 mRNA.The study reveals the role of FTO in H/R-induced myocardial cell injury via m6A-dependent manner, which provided a new approach to improve myocardial IRI.

Transcriptional enhancer factor TEF-4 (TEAD2)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by FTO*
Cell Line	Cerebral cortex	Mus musculus
Treatment: METTL3 (f/f, Emx1-cre) cerebral cortex Control: Wild type cerebral cortex		GSE154992
Regulation		logFC: 6.75E-01 p-value: 4.59E-03
More Results	Click to View More RNA-seq Results

Liver cancer [ICD-11: 2C12]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[60]
Responsed Disease	Intrahepatic cholangiocarcinoma [ICD-11: 2C12.10]
Target Regulation	Down regulation
Cell Process	Cell cycle
Cell Process	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
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.

Transgelin (SM22alpha)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by FTO*
Cell Line	TPC_1 cell line	Homo sapiens
Treatment: FTO overexpression TPC_1 cells Control: TPC_1 cells		GSE199206
Regulation		logFC: 6.14E-01 p-value: 1.66E-07
More Results	Click to View More RNA-seq Results

Type 2 diabetes mellitus [ICD-11: 5A11]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[61]
Responsed Disease	Type 2 diabetes mellitus [ICD-11: 5A11]
Target Regulation	Down regulation
In-vitro Model	VSMC (Human aortic vascular smooth muscle cells)
Response Summary	FTO knockdown elevated Transgelin (SM22alpha) expression and m6A-binding protein IGF2BP2 enhanced SM22alpha mRNA stability by recognizing and binding to m6A methylation modified mRNA. m6A methylation-mediated elevation of SM22alpha restrained VSMC proliferation and migration and ameliorated intimal hyperplasia in T2DM.

Ubiquitin-like modifier-activating enzyme ATG7 (ATG7)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by FTO*
Cell Line	NB4 cell line	Homo sapiens
Treatment: shFTO NB4 cells Control: shNS NB4 cells		GSE103494
Regulation		logFC: 1.18E+00 p-value: 1.81E-03
More Results	Click to View More RNA-seq Results

Malignant mixed epithelial mesenchymal tumour [ICD-11: 2B5D]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[62]
Responsed Disease	Malignant mixed epithelial mesenchymal tumour of ovary [ICD-11: 2B5D.0]
Target Regulation	Up regulation
Pathway Response	Autophagy			hsa04140
Cell Process	Cell autophagy
In-vitro Model	SK-OV-3	Ovarian serous cystadenocarcinoma	Homo sapiens	CVCL_0532
In-vivo Model	The SKOV3 ovarian cancer cell line was transfected with LV2-1 or LV2-NC. Thereafter, BALB/c nude mice (6-week old) were intraperitoneally injected with SKOV3 cells. The mice were killed after 5 weeks, and the number of ascites was determined.
Response Summary	CircRAB11FIP1 promoted autophagy flux of ovarian cancer through DSC1 and miR-129. CircRAB11FIP1 can serve as the possible marker for EOC diagnosis and treatment. CircRAB11FIP1 regulated the mechanism of autophagy through m6A modification and direct binding to mRNA. CircRAB11FIP1 bound to the mRNA of FTO and promoted its expression. CircRAB11FIP1 directly bound to miR-129 and regulated its targets Ubiquitin-like modifier-activating enzyme ATG7 (ATG7) and ATG14. CircRAB11FIP1 bound to desmocollin 1to facilitate its interaction with ATG101. CircRAB11FIP1 mediated mRNA expression levels of ATG5 and ATG7 depending on m6A.

Obesity [ICD-11: 5B81]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[63]
Responsed Disease	Obesity [ICD-11: 5B81]
Target Regulation	Up regulation
Pathway Response	Autophagy			hsa04140
Cell Process	Autophagy
	Adipogenesis regulation
In-vitro Model	3T3-L1	Normal	Mus musculus	CVCL_0123
	Pig primary preadipocytes (Isolated from cervical subcutaneous adipose tissue of piglets)
In-vivo Model	Mice were maintained at 22 ± 2 ℃ with a humidity of 35 ± 5% under a 12 h light and 12 h dark cycle, with free access to water and food. For the HFD experiment, female control (Fto^flox/flox) and adipose-selective fto knockout (Fabp4-Cre Fto^flox/flox, fto-AKO) mice were fed with high-fat diet (60% fat in calories; Research Diets, D12492) for the desired periods of time, and food intake and body weight were measured every week after weaning (at 3 weeks of age).
Response Summary	Atg5 and Ubiquitin-like modifier-activating enzyme ATG7 (ATG7) were the targets of YTHDF2 (YTH N6-methyladenosine RNA binding protein 2). Upon FTO silencing, Atg5 and Atg7 transcripts with higher m6A levels were captured by YTHDF2, which resulted in mRNA degradation and reduction of protein expression, thus alleviating autophagy and adipogenesis.

Vascular cell adhesion protein 1 (VCAM1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by FTO*
Cell Line	Mouse hippocampus	Mus musculus
Treatment: FTO knockout mice hippocampus Control: Wild type hippocampus		GSE94098
Regulation		logFC: 6.17E-01 p-value: 3.60E-03
More Results	Click to View More RNA-seq Results

Diseases of the circulatory system [ICD-11: BE2Z]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[29]
Responsed Disease	Vascular diseases [ICD-11: BE2Z]
Responsed Drug	Atorvastatin		Approved	Drug Info
Target Regulation	Up regulation
In-vitro Model	THP-1	Childhood acute monocytic leukemia	Homo sapiens	CVCL_0006
	HUVEC-C	Normal	Homo sapiens	CVCL_2959
	HEK293T	Normal	Homo sapiens	CVCL_0063
Response Summary	FTO overexpression significantly upregulated the mRNA and protein levels of Vascular cell adhesion protein 1 (VCAM1) and ICAM-1, downregulated those of KLF2 and eNOS, and strongly attenuated the atorvastatin-mediated induction of KLF2 and eNOS expression. FTO could serve as a novel molecular target to modulate endothelial function in vascular diseases.

Metastasis associated lung adenocarcinoma transcript 1 (MALAT1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by FTO*
Cell Line	NB4 cell line	Homo sapiens
Treatment: shFTO NB4 cells Control: shNS NB4 cells		GSE103494
Regulation		logFC: 8.67E-01 p-value: 5.83E-03
More Results	Click to View More RNA-seq Results

Bladder cancer [ICD-11: 2C94]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[27]
Responsed Disease	Bladder cancer [ICD-11: 2C94]
Target Regulation	Down regulation
Pathway Response	Notch signaling pathway			hsa04330
Cell Process	Cell proliferation
	Cell invasion
	Cell apoptosis
In-vitro Model	HT-1197	Recurrent bladder carcinoma	Homo sapiens	CVCL_1291
	HT-1376	Bladder carcinoma	Homo sapiens	CVCL_1292
In-vivo Model	BALB/cnu/nu mice (4-5 weeks old) were used for the xenograft experiment. The mice were randomly divided into 2 groups (n = 6 for each group) and injected with 5 × 10⁶ HT-1197 cells in control group or FTO plasmid group, respectively.
Response Summary	In bladder cancer, the changes in m6A methylation level mainly appeared at 5' untranslated region (5' UTR) of Metastasis associated lung adenocarcinoma transcript 1 (MALAT1) and NOTCH1 transcripts, and at 3' UTR of CSNK2A2 and ITGA6 transcripts, responding to the overexpression of FTO. SFPQ could influence the FTO-mediated m6A RNA demethylation, eventually affecting the gene expression.

Kidney failure [ICD-11: GB6Z]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[65]
Responsed Disease	Kidney failure [ICD-11: GB6Z]
Target Regulation	Up regulation
In-vitro Model	NIT-1	Insulin tumor	Mus musculus	CVCL_3561
Response Summary	m6A modification is co-regulated by METTL3 and FTO in cadmium-treated cells. Metastasis associated lung adenocarcinoma transcript 1 (MALAT1), LncRNA-PVT1 and m6A modification could be key nodes for cadmium-induced oxidative damage, and highlight their importance as promising preventive and therapeutic targets in cadmium toxicity.

Autophagy protein 5 (ATG5)

Target Gene

Malignant mixed epithelial mesenchymal tumour [ICD-11: 2B5D]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[62]
Responsed Disease	Malignant mixed epithelial mesenchymal tumour of ovary [ICD-11: 2B5D.0]
Target Regulation	Up regulation
Pathway Response	Autophagy			hsa04140
Cell Process	Cell autophagy
In-vitro Model	SK-OV-3	Ovarian serous cystadenocarcinoma	Homo sapiens	CVCL_0532
In-vivo Model	The SKOV3 ovarian cancer cell line was transfected with LV2-1 or LV2-NC. Thereafter, BALB/c nude mice (6-week old) were intraperitoneally injected with SKOV3 cells. The mice were killed after 5 weeks, and the number of ascites was determined.
Response Summary	CircRAB11FIP1 promoted autophagy flux of ovarian cancer through DSC1 and miR-129. CircRAB11FIP1 can serve as the possible marker for EOC diagnosis and treatment. CircRAB11FIP1 regulated the mechanism of autophagy through m6A modification and direct binding to mRNA. CircRAB11FIP1 bound to the mRNA of FTO and promoted its expression. CircRAB11FIP1 directly bound to miR-129 and regulated its targets ATG7 and ATG14. CircRAB11FIP1 bound to desmocollin 1to facilitate its interaction with ATG101. CircRAB11FIP1 mediated mRNA expression levels of Autophagy protein 5 (ATG5) and ATG7 depending on m6A.

Obesity [ICD-11: 5B81]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[63]
Responsed Disease	Obesity [ICD-11: 5B81]
Target Regulation	Up regulation
Pathway Response	Autophagy			hsa04140
Cell Process	Autophagy
	Adipogenesis regulation
In-vitro Model	3T3-L1	Normal	Mus musculus	CVCL_0123
	Pig primary preadipocytes (Isolated from cervical subcutaneous adipose tissue of piglets)
In-vivo Model	Mice were maintained at 22 ± 2 ℃ with a humidity of 35 ± 5% under a 12 h light and 12 h dark cycle, with free access to water and food. For the HFD experiment, female control (Fto^flox/flox) and adipose-selective fto knockout (Fabp4-Cre Fto^flox/flox, fto-AKO) mice were fed with high-fat diet (60% fat in calories; Research Diets, D12492) for the desired periods of time, and food intake and body weight were measured every week after weaning (at 3 weeks of age).
Response Summary	Autophagy protein 5 (ATG5) and Atg7 were the targets of YTHDF2 (YTH N6-methyladenosine RNA binding protein 2). Upon FTO silencing, Atg5 and Atg7 transcripts with higher m6A levels were captured by YTHDF2, which resulted in mRNA degradation and reduction of protein expression, thus alleviating autophagy and adipogenesis.

Autophagy-related protein 101 (ATG101)

Target Gene

Malignant mixed epithelial mesenchymal tumour [ICD-11: 2B5D]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[62]
Responsed Disease	Malignant mixed epithelial mesenchymal tumour of ovary [ICD-11: 2B5D.0]
Target Regulation	Up regulation
Pathway Response	Autophagy			hsa04140
Cell Process	Cell autophagy
In-vitro Model	SK-OV-3	Ovarian serous cystadenocarcinoma	Homo sapiens	CVCL_0532
In-vivo Model	The SKOV3 ovarian cancer cell line was transfected with LV2-1 or LV2-NC. Thereafter, BALB/c nude mice (6-week old) were intraperitoneally injected with SKOV3 cells. The mice were killed after 5 weeks, and the number of ascites was determined.
Response Summary	CircRAB11FIP1 promoted autophagy flux of ovarian cancer through DSC1 and miR-129. CircRAB11FIP1 can serve as the possible marker for EOC diagnosis and treatment. CircRAB11FIP1 regulated the mechanism of autophagy through m6A modification and direct binding to mRNA. CircRAB11FIP1 bound to the mRNA of FTO and promoted its expression. CircRAB11FIP1 directly bound to miR-129 and regulated its targets ATG7 and ATG14. CircRAB11FIP1 bound to desmocollin 1to facilitate its interaction with Autophagy-related protein 101 (ATG101). CircRAB11FIP1 mediated mRNA expression levels of ATG5 and ATG7 depending on m6A.

Beclin 1-associated autophagy-related key regulator (ATG14)

Target Gene

Malignant mixed epithelial mesenchymal tumour [ICD-11: 2B5D]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[62]
Responsed Disease	Malignant mixed epithelial mesenchymal tumour of ovary [ICD-11: 2B5D.0]
Target Regulation	Up regulation
Pathway Response	Autophagy			hsa04140
Cell Process	Cell autophagy
In-vitro Model	SK-OV-3	Ovarian serous cystadenocarcinoma	Homo sapiens	CVCL_0532
In-vivo Model	The SKOV3 ovarian cancer cell line was transfected with LV2-1 or LV2-NC. Thereafter, BALB/c nude mice (6-week old) were intraperitoneally injected with SKOV3 cells. The mice were killed after 5 weeks, and the number of ascites was determined.
Response Summary	CircRAB11FIP1 promoted autophagy flux of ovarian cancer through DSC1 and miR-129. CircRAB11FIP1 can serve as the possible marker for EOC diagnosis and treatment. CircRAB11FIP1 regulated the mechanism of autophagy through m6A modification and direct binding to mRNA. CircRAB11FIP1 bound to the mRNA of FTO and promoted its expression. CircRAB11FIP1 directly bound to miR-129 and regulated its targets ATG7 and Beclin 1-associated autophagy-related key regulator (ATG14). CircRAB11FIP1 bound to desmocollin 1to facilitate its interaction with ATG101. CircRAB11FIP1 mediated mRNA expression levels of ATG5 and ATG7 depending on m6A.

Casein kinase II subunit alpha' (CSNK2A2)

Target Gene

Bladder cancer [ICD-11: 2C94]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[27]
Responsed Disease	Bladder cancer [ICD-11: 2C94]
Target Regulation	Up regulation
Pathway Response	Notch signaling pathway			hsa04330
Cell Process	Cell proliferation
	Cell invasion
	Cell apoptosis
In-vitro Model	HT-1197	Recurrent bladder carcinoma	Homo sapiens	CVCL_1291
	HT-1376	Bladder carcinoma	Homo sapiens	CVCL_1292
In-vivo Model	BALB/cnu/nu mice (4-5 weeks old) were used for the xenograft experiment. The mice were randomly divided into 2 groups (n = 6 for each group) and injected with 5 × 10⁶ HT-1197 cells in control group or FTO plasmid group, respectively.
Response Summary	In bladder cancer, the changes in m6A methylation level mainly appeared at 5' untranslated region (5' UTR) of MALAT1 and NOTCH1 transcripts, and at 3' UTR of Casein kinase II subunit alpha' (CSNK2A2) and ITGA6 transcripts, responding to the overexpression of FTO. SFPQ could influence the FTO-mediated m6A RNA demethylation, eventually affecting the gene expression.

Catenin beta-1 (CTNNB1/Beta-catenin)

Target Gene

Head and neck squamous carcinoma [ICD-11: 2B6E]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[66]
Responsed Disease	Head and neck squamous carcinoma [ICD-11: 2B6E]
Target Regulation	Up regulation
Pathway Response	Adherens junction			hsa04520
Cell Process	Cell proliferation and migration
In-vitro Model	CAL-27	Tongue squamous cell carcinoma	Homo sapiens	CVCL_1107
	FaDu	Hypopharyngeal squamous cell carcinoma	Homo sapiens	CVCL_1218
	Tu 686	Laryngeal squamous cell carcinoma	Homo sapiens	CVCL_4916
	HN-6	Tongue squamous cell carcinoma	Homo sapiens	CVCL_8129
	HEp-2	Endocervical adenocarcinoma	Homo sapiens	CVCL_1906
Response Summary	FTO expression was significantly upregulated in HNSCC datasets and tissues. FTO expression was significantly correlated with Catenin beta-1 (CTNNB1/Beta-catenin) expression. Moreover, it exerted a tumorigenic effect by increasing CTNNB1 expression in an m6A-dependent manner.

Cervical intraepithelial neoplasia [ICD-11: 2E66]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[67]
Responsed Disease	Cervical squamous cell carcinoma [ICD-11: 2E66.2]
Target Regulation	Up regulation
Cell Process	RNA decay
In-vitro Model	C-33 A	Cervical squamous cell carcinoma	Homo sapiens	CVCL_1094
In-vitro Model	SiHa	Cervical squamous cell carcinoma	Homo sapiens	CVCL_0032
In-vivo Model	Either SiHa cells or FTO overexpressed SiHa cells were injected subcutaneously into the right flanks of 4- to 6-week-old female athymic nude mice (CAS, Beijing, China). The mice were divided into four groups (N = 6). After transplantation, tumor size was measured by caliper every other day. Tumor volume was calculated using the formula: volume = (length × width²)/2. When the tumor volumes reached 50 mm³, the animals were treated with intraperitoneal injection of cisplatin (3 mg/kg) every other day for seven times and local irradiation of 8 Gy one time.
Response Summary	The mRNA level of FTO is elevated in cervical squamous cell carcinoma (CSCC) tissues when compared with respective adjacent normal tissues.FTO enhances the chemo-radiotherapy resistance both in vitro and in vivo through regulating expression of Catenin beta-1 (CTNNB1/Beta-catenin) by reducing m6A levels in its mRNA transcripts and in turn increases excision repair cross-complementation group 1 (ERCC1) activity.

Cellular tumor antigen p53 (TP53/p53)

Target Gene

Acute kidney failure [ICD-11: GB60]

In total 2 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[68]
Responsed Disease	Acute kidney failure [ICD-11: GB60]
Responsed Drug	Cisplatin		Approved	Drug Info
Target Regulation	Down regulation
Pathway Response	Apoptosis			hsa04210
Cell Process	Cell apoptosis
In-vitro Model	HK2	Normal	Acipenser baerii	CVCL_YE28
In-vivo Model	Induced AKI in c57BL/6 mice by intraperitoneal cisplatin injection and treated the animal with vehicle or an FTO inhibitor meclofenamic acid (MA) for 3 days.
Response Summary	Meclofenamic acid increased Cellular tumor antigen p53 (TP53/p53) mRNA and protein levels in AKI both in vitro and in vivo, and FTO overexpression reduced p53 expression and reversed the MA-induced p53 increase in cisplatin-induced acute kidney injury Acute kidney injury.
Experiment 2 Reporting the m6A-centered Disease Response of This Target Gene				[68]
Responsed Disease	Acute kidney failure [ICD-11: GB60]
Responsed Drug	Meclofenamic acid		Approved	Drug Info
Target Regulation	Down regulation
Pathway Response	Apoptosis			hsa04210
Cell Process	Cell apoptosis
In-vitro Model	HK2	Normal	Acipenser baerii	CVCL_YE28
In-vivo Model	Induced AKI in c57BL/6 mice by intraperitoneal cisplatin injection and treated the animal with vehicle or an FTO inhibitor meclofenamic acid (MA) for 3 days.
Response Summary	Meclofenamic acid increased Cellular tumor antigen p53 (TP53/p53) mRNA and protein levels in AKI both in vitro and in vivo, and FTO overexpression reduced p53 expression and reversed the MA-induced p53 increase in cisplatin-induced Acute kidney injury.

Chloride intracellular channel protein 4 (CLIC4)

Target Gene

Prostate cancer [ICD-11: 2C82]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[69]
Responsed Disease	Prostate cancer [ICD-11: 2C82]
Target Regulation	Up regulation
In-vitro Model	RWPE-1	Normal	Homo sapiens	CVCL_3791
	PC-3	Prostate carcinoma	Homo sapiens	CVCL_0035
	DU145	Prostate carcinoma	Homo sapiens	CVCL_0105
	LNCaP C4-2	Prostate carcinoma	Homo sapiens	CVCL_4782
In-vivo Model	Approximately 2×10⁶ PCa cells (DU145 transfected with shFTO and shNC) were injected subcutaneously in mice. The tumor volume (V = (0.5lengthwidth²)) was measured with Vernier caliper every week. Ten mice were randomly divided into two groups, 2×10⁶ cells transfected with shFTO and shNC were resuspended with 100 uL PBS and injected into the mouse tail vein to create a metastatic model. After 7 weeks, the mice were anesthetized, and D-luciferin (#D-Luciferin, Apexbio) was injected intraperitoneally, then used the IVIS imaging system (Caliper Life Sciences) to visualize the luciferase signal.
Response Summary	FTO suppresses PCa proliferation and metastasis through reducing the degradation of Chloride intracellular channel protein 4 (CLIC4) mRNA in an m6A dependent manner.

Constitutive NOS (eNOS)

Target Gene

Diseases of the circulatory system [ICD-11: BE2Z]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[29]
Responsed Disease	Vascular diseases [ICD-11: BE2Z]
Responsed Drug	Atorvastatin		Approved	Drug Info
Target Regulation	Down regulation
In-vitro Model	THP-1	Childhood acute monocytic leukemia	Homo sapiens	CVCL_0006
	HUVEC-C	Normal	Homo sapiens	CVCL_2959
	HEK293T	Normal	Homo sapiens	CVCL_0063
Response Summary	FTO overexpression significantly upregulated the mRNA and protein levels of VCAM-1 and ICAM-1, downregulated those of KLF2 and Constitutive NOS (eNOS), and strongly attenuated the atorvastatin-mediated induction of KLF2 and eNOS expression. FTO could serve as a novel molecular target to modulate endothelial function in vascular diseases.

Cyclin-dependent kinase 6 (CDK6)

Target Gene

Bladder cancer [ICD-11: 2C94]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[70]
Responsed Disease	Bladder cancer [ICD-11: 2C94]
Target Regulation	Up regulation
Cell Process	Cell proliferation
	Cell migration
	Cell invasion
In-vitro Model	5637	Bladder carcinoma	Homo sapiens	CVCL_0126
	T24	Bladder carcinoma	Homo sapiens	CVCL_0554
	UM-UC-3	Bladder carcinoma	Homo sapiens	CVCL_1783
In-vivo Model	Approximately 1 × 10⁷ stably transfected T24 cells were subcutaneously injected into BALB/c nude mice. The length (L) and width (W) of the tumours were measured weekly using callipers, while their volume was calculated using the equation: V = (L × W2)/2. After 4 weeks of injections, the mice were euthanised, and the tumour tissues were removed and weighed.
Response Summary	FTO promoted bladder cancer cell proliferation, migration and invasion via the FTO/miR-576/Cyclin-dependent kinase 6 (CDK6) pathways in an m6A-dependent manner.

Cytochrome P450 2C8 (CYP2C8)

Target Gene

Liver cancer [ICD-11: 2C12]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[71]
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
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
In-vitro Model	Huh-7	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0336
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.

Desmocollin-1 (DSC1)

Target Gene

Malignant mixed epithelial mesenchymal tumour [ICD-11: 2B5D]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[62]
Responsed Disease	Malignant mixed epithelial mesenchymal tumour of ovary [ICD-11: 2B5D.0]
Pathway Response	Autophagy			hsa04140
Cell Process	Cell autophagy
In-vitro Model	SK-OV-3	Ovarian serous cystadenocarcinoma	Homo sapiens	CVCL_0532
In-vivo Model	The SKOV3 ovarian cancer cell line was transfected with LV2-1 or LV2-NC. Thereafter, BALB/c nude mice (6-week old) were intraperitoneally injected with SKOV3 cells. The mice were killed after 5 weeks, and the number of ascites was determined.
Response Summary	CircRAB11FIP1 promoted autophagy flux of ovarian cancer through Desmocollin-1 (DSC1) and miR-129. CircRAB11FIP1 can serve as the possible marker for EOC diagnosis and treatment. CircRAB11FIP1 regulated the mechanism of autophagy through m6A modification and direct binding to mRNA. CircRAB11FIP1 bound to the mRNA of FTO and promoted its expression. CircRAB11FIP1 directly bound to miR-129 and regulated its targets ATG7 and ATG14. CircRAB11FIP1 bound to desmocollin 1to facilitate its interaction with ATG101. CircRAB11FIP1 mediated mRNA expression levels of ATG5 and ATG7 depending on m6A.

DNA excision repair protein ERCC-1 (ERCC1)

Target Gene

Cervical intraepithelial neoplasia [ICD-11: 2E66]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[67]
Responsed Disease	Cervical squamous cell carcinoma [ICD-11: 2E66.2]
Target Regulation	Up regulation
Cell Process	RNA decay
In-vitro Model	C-33 A	Cervical squamous cell carcinoma	Homo sapiens	CVCL_1094
In-vitro Model	SiHa	Cervical squamous cell carcinoma	Homo sapiens	CVCL_0032
In-vivo Model	Either SiHa cells or FTO overexpressed SiHa cells were injected subcutaneously into the right flanks of 4- to 6-week-old female athymic nude mice (CAS, Beijing, China). The mice were divided into four groups (N = 6). After transplantation, tumor size was measured by caliper every other day. Tumor volume was calculated using the formula: volume = (length × width²)/2. When the tumor volumes reached 50 mm³, the animals were treated with intraperitoneal injection of cisplatin (3 mg/kg) every other day for seven times and local irradiation of 8 Gy one time.
Response Summary	The mRNA level of FTO is elevated in cervical squamous cell carcinoma (CSCC) tissues when compared with respective adjacent normal tissues.FTO enhances the chemo-radiotherapy resistance both in vitro and in vivo through regulating expression of beta-catenin by reducing m6A levels in its mRNA transcripts and in turn increases DNA excision repair protein ERCC-1 (ERCC1) activity.

DNA polymerase kappa (Pol Kappa/POLK)

Target Gene

Exposure to radiation [ICD-11: PH73]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[72]
Responsed Disease	Exposure to radiation [ICD-11: PH73]
Target Regulation	Up regulation
Cell Process	DNA repair
Cell Process	Nucleotide excision repair (hsa03420)
In-vitro Model	A-375	Amelanotic melanoma	Homo sapiens	CVCL_0132
	U2OS	Osteosarcoma	Homo sapiens	CVCL_0042
	HEK293T	Normal	Homo sapiens	CVCL_0063
	HeLa	Endocervical adenocarcinoma	Homo sapiens	CVCL_0030
	MEF (Mouse embryonic fibroblasts)
	U2OS	Osteosarcoma	Homo sapiens	CVCL_0042
Response Summary	Methylation at the 6 position of adenosine (m6A) in RNA is rapidly (within 2 min) and transiently induced at DNA damage sites in response to ultraviolet irradiation. This modification occurs on numerous poly(A)+ transcripts and is regulated by the methyltransferase METTL3 and the demethylase FTO. DNA DNA polymerase kappa (Pol Kappa/POLK), which has been implicated in both nucleotide excision repair and trans-lesion synthesis, required the catalytic activity of METTL3 for immediate localization to ultraviolet-induced DNA damage sites.

E3 ubiquitin-protein ligase NEDD4-like (NEDD4L)

Target Gene

Solid tumour/cancer [ICD-11: 2A00-2F9Z]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[53]
Responsed Disease	Solid tumour/cancer [ICD-11: 2A00-2F9Z]
Pathway Response	Autophagy			hsa04140
Cell Process	Cellular Processes, Transport and catabolism
	Cell autophagy
In-vitro Model	HaCaT	Normal	Homo sapiens	CVCL_0038
	HEK293T	Normal	Homo sapiens	CVCL_0063
	HeLa	Endocervical adenocarcinoma	Homo sapiens	CVCL_0030
	MEF (Mouse embryonic fibroblasts)
In-vivo Model	As cells (5 million) in Matrigel or As-T (1 million) cells in PBS with or without gene manipulations were injected subcutaneously into the right flanks of female mice (6-8 weeks of age). For treatment with CS1 or CS2, As-T cells (1 million) in PBS were injected subcutaneously into the right flanks of 6-week-old female nude mice.
Response Summary	FTO deletion inhibited arsenic-induced tumorigenesis. Epidermis-specific FTO deletion prevented skin tumorigenesis induced by arsenic and UVB irradiation. E3 ubiquitin-protein ligase NEDD4-like (NEDD4L) was identified as the m6A-modified gene target of FTO. Arsenic stabilizes FTO protein through inhibiting p62-mediated selective autophagy. FTO-mediated dysregulation of mRNA m6A methylation as an epitranscriptomic mechanism to promote arsenic tumorigenicity. Arsenic suppresses p62 expression by downregulating the NF-Kappa-B pathway to upregulate FTO.

Human skin lesions [ICD-11: ME60]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[53]
Responsed Disease	Human skin lesions [ICD-11: ME60]
Pathway Response	Autophagy			hsa04140
Cell Process	Cellular Processes, Transport and catabolism
	Cell autophagy
In-vitro Model	HaCaT	Normal	Homo sapiens	CVCL_0038
	HEK293T	Normal	Homo sapiens	CVCL_0063
	HeLa	Endocervical adenocarcinoma	Homo sapiens	CVCL_0030
	MEF (Mouse embryonic fibroblasts)
In-vivo Model	As cells (5 million) in Matrigel or As-T (1 million) cells in PBS with or without gene manipulations were injected subcutaneously into the right flanks of female mice (6-8 weeks of age). For treatment with CS1 or CS2, As-T cells (1 million) in PBS were injected subcutaneously into the right flanks of 6-week-old female nude mice.
Response Summary	FTO deletion inhibited arsenic-induced tumorigenesis. Epidermis-specific FTO deletion prevented skin tumorigenesis induced by arsenic and UVB irradiation. E3 ubiquitin-protein ligase NEDD4-like (NEDD4L) was identified as the m6A-modified gene target of FTO. Arsenic stabilizes FTO protein through inhibiting p62-mediated selective autophagy. FTO-mediated dysregulation of mRNA m6A methylation as an epitranscriptomic mechanism to promote arsenic tumorigenicity. Arsenic suppresses p62 expression by downregulating the NF-Kappa-B pathway to upregulate FTO.

Estradiol 17-beta-dehydrogenase 11 (HSD17B11)

Target Gene

Esophageal cancer [ICD-11: 2B70]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[73]
Responsed Disease	Esophageal cancer [ICD-11: 2B70]
Target Regulation	Up regulation
Cell Process	Lipid metabolism
In-vitro Model	TE-1	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1759
In-vitro Model	KYSE-510	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1354
In-vivo Model	Nude mice were randomly divided into five groups of six mice each, and the mice in each group were received subcutaneous injections of shFTO, scrambled shNC, FTO OE, and vector KYSE510 cells (5×10⁶ tumor cells/mouse), respectively. The tumor size and weight of mice were measured 1 week later, which was recorded as day 0, and then measured once every other day; and the tumor volumes were calculated using the following formula: (length×width2)/2.When the tumor maximum diameter was close to 15 mm, the mice were euthanized and the tumor tissues were collected for immunohistochemistry analysis.
Response Summary	FTO relys on the reading protein YTHDF1 to affect the translation pathway of the Estradiol 17-beta-dehydrogenase 11 (HSD17B11) gene to regulate the formation of lipid droplets in esophageal cancer cells.

Eukaryotic translation initiation factor 4 gamma 1 (EIF4G1)

Target Gene

Head and neck squamous carcinoma [ICD-11: 2B6E]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[74]
Responsed Disease	Oral squamous cell carcinoma [ICD-11: 2B6E.0]
Target Regulation	Up regulation
Pathway Response	Autophagy	hsa04140
Cell Process	Cell autophagy
Response Summary	Rapamycin inhibited FTO activity, and directly targeted Eukaryotic translation initiation factor 4 gamma 1 (EIF4G1) transcripts and mediated their expression in an m6A-dependent manner in oral squamous cell carcinoma. After FTO silencing, YTHDF2 captured eIF4G1 transcripts containing m6A, resulting in mRNA degradation and decreased expression of eIF4G1 protein, thereby promoting autophagy and reducing tumor occurrence.

Fatty acid synthase (FASN)

Target Gene

Solid tumour/cancer [ICD-11: 2A00-2F9Z]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[75]
Responsed Disease	Solid tumour/cancer [ICD-11: 2A00-2F9Z]
Target Regulation	Down regulation
Cell Process	Deficiency of lipid accumulation
	Cellular apoptosis
In-vitro Model	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
Response Summary	FTO regulates hepatic lipogenesis via FTO-dependent m6A demethylation in Fatty acid synthase (FASN) mRNA and indicate the critical role of FTO-mediated lipid metabolism in the survival of HepG2 cells. This study provides novel insights into a unique RNA epigenetic mechanism by which FTO mediates hepatic lipid accumulation through m6 A modification and indicates that FTO could be a potential target for obesity-related diseases and cancer.

Diabetes [ICD-11: 5A10-5A14]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[18]
Responsed Disease	Diabetes [ICD-11: 5A10-5A14]
Pathway Response	Metabolic pathways			hsa01100
	Fatty acid metabolism			hsa01212
Cell Process	Lipid metabolism
In-vitro Model	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
Response Summary	Glucose Is Involved in the Dynamic Regulation of m6A in Patients With Type 2 Diabetes.high-glucose stimulation enhances FTO expression, which leads to decreased m6A, and the lower m6A induces methyltransferase upregulation; FTO then triggers the mRNA expression of FOXO1, Fatty acid synthase (FASN), G6PC, and DGAT2, and these four genes were correlated with glucose and lipid metabolism.

Obesity [ICD-11: 5B81]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[75]
Responsed Disease	Obesity [ICD-11: 5B81]
Target Regulation	Down regulation
Cell Process	Deficiency of lipid accumulation
	Cellular apoptosis
In-vitro Model	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
Response Summary	FTO regulates hepatic lipogenesis via FTO-dependent m6A demethylation in Fatty acid synthase (FASN) mRNA and indicate the critical role of FTO-mediated lipid metabolism in the survival of HepG2 cells. This study provides novel insights into a unique RNA epigenetic mechanism by which FTO mediates hepatic lipid accumulation through m6 A modification and indicates that FTO could be a potential target for obesity-related diseases and cancer.

Flotillin-2 (FLOT2)

Target Gene

Ovarian dysfunction [ICD-11: 5A80]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[76]
Responsed Disease	Polycystic ovary syndrome [ICD-11: 5A80.1]
Target Regulation	Up regulation
Cell Process	Cell apoptosis
In-vitro Model	KGN	Ovarian granulosa cell tumor	Homo sapiens	CVCL_0375
Response Summary	FTO induced the dysfunctions of GCs by upregulating Flotillin-2 (FLOT2), suggesting that FTO/FLOT2 plays a role in the pathophysiology of polycystic ovarian syndrome.

Forkhead box protein O1 (FOXO1)

Target Gene

Diabetes [ICD-11: 5A10-5A14]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[18]
Responsed Disease	Diabetes [ICD-11: 5A10-5A14]
Cell Process	Lipid metabolism
In-vitro Model	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
Response Summary	Glucose Is Involved in the Dynamic Regulation of m6A in Patients with Type 2 Diabetes. High-glucose stimulation enhances FTO expression, which leads to decreased m6A, and the lower m6A induces methyltransferase upregulation; FTO then triggers the mRNA expression of Forkhead box protein O1 (FOXO1), FASN, G6PC, and DGAT2, and these four genes were correlated with glucose and lipid metabolism.

Glucose-6-phosphatase catalytic subunit 1 (G6PC/G6PC1)

Target Gene

Diabetes [ICD-11: 5A10-5A14]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[18]
Responsed Disease	Diabetes [ICD-11: 5A10-5A14]
Pathway Response	Metabolic pathways			hsa01100
	Glycolysis / Gluconeogenesis			hsa00010
Cell Process	Lipid metabolism
In-vitro Model	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
Response Summary	Glucose Is Involved in the Dynamic Regulation of m6A in Patients With Type 2 Diabetes.high-glucose stimulation enhances FTO expression, which leads to decreased m6A, and the lower m6A induces methyltransferase upregulation; FTO then triggers the mRNA expression of FOXO1, FASN, Glucose-6-phosphatase catalytic subunit 1 (G6PC/G6PC1), and DGAT2, and these four genes were correlated with glucose and lipid metabolism.

Glucose-6-phosphate dehydrogenase (G6PD)

Target Gene

Colorectal cancer [ICD-11: 2B91]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[77]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulation	Up regulation
Pathway Response	Glutathione metabolism			hsa00480
In-vitro Model	LoVo	Colon adenocarcinoma	Homo sapiens	CVCL_0399
	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	HCT 8	Colon adenocarcinoma	Homo sapiens	CVCL_2478
	SW620	Colon adenocarcinoma	Homo sapiens	CVCL_0547
In-vivo Model	For CDX model, nude mice (female, 4-6-week-old) were subcutaneously injected with 5 × 10⁶ HCT116 cells on the both flank. For PDX model, the patient tumors were divided into small pieces and then inoculated on both flank of nude mice. For knockdown FTO mice model, FTO mice model, two weeks after inoculation, the shFTO#3 lenti-virus injected into the tumor for three consecutive days. For combined medication mice model, intraperitoneal injection of Rhein and Olaparib was started one week after inoculation
Response Summary	Targeting FTO significantly suppresses cancer cell growth and enhances chemotherapy sensitivity, which not only mediating the balance of intracellular ROS by regulating Glucose-6-phosphate dehydrogenase (G6PD) expression, but also maintaining genome instability by regulating PARP1 expression. These findings shed light on new molecular mechanisms of CRC development and treatments mediated by m6A modification.

Histone-lysine N-methyltransferase EHMT2 (G9a)

Target Gene

Pain disorders [ICD-11: 8E43]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[78]
Responsed Disease	Neuropathic Pain [ICD-11: 8E43.0]
Target Regulation	Up regulation
In-vitro Model	PC12	Rat adrenal gland pheochromocytoma	Rattus norvegicus	CVCL_0481
In-vivo Model	After the animal was anesthetized with isoflurane, a midline incision in the lower lumbar back region was made and the lumbar articular process was exposed and then removed. The exposed DRG was injected with viral solution (1-1.5 ul in rats and 0.5-1 ul in mice) through a glass micropipette connected to a Hamilton syringe. The pipette was retained for 10 min after injection. Animals showing signs of paresis or other abnormalities were excluded. The injected DRGs were stained with hematoxylin/eosin to examine the integrity of their structure and whether they contained visible leukocytes.
Response Summary	FTO contributes to neuropathic pain through stabilizing nerve injury-induced upregulation of Histone-lysine N-methyltransferase EHMT2 (G9a), a neuropathic pain initiator, in primary sensory neurons.

Homeobox protein Hox-B13 (HOXB13)

Target Gene

Gastric cancer [ICD-11: 2B72]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[79]
Responsed Disease	Gastric cancer [ICD-11: 2B72]
Target Regulation	Down regulation
Pathway Response	PI3K-Akt signaling pathway			hsa04151
Pathway Response	mTOR signaling pathway			hsa04150
Cell Process	Cell proliferation
	Cell migration
	Cell invasion
In-vitro Model	SNU-5	Gastric adenocarcinoma	Homo sapiens	CVCL_0078
	NCI-N87	Gastric tubular adenocarcinoma	Homo sapiens	CVCL_1603
	MKN45	Gastric adenocarcinoma	Homo sapiens	CVCL_0434
	GES-1	Normal	Homo sapiens	CVCL_EQ22
	AGS	Gastric adenocarcinoma	Homo sapiens	CVCL_0139
In-vivo Model	Male nu/nu mice between 4 and 6 weeks of age received subcutaneous injections of equivalent AGS cells expressing either control or LV-HOXB13 within 30 min of harvesting on the right and left flanks.
Response Summary	FTO suppresses Homeobox protein Hox-B13 (HOXB13) methytlation; FTO and HOXB13 expression promotes GC cell proliferation, migration, and invasion. HOXB13 expression intensifies GC invasion through PI3K/AKT/mTOR signaling via IGF-1R.

Endometrial cancer [ICD-11: 2C76]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[80]
Responsed Disease	Endometrial cancer [ICD-11: 2C76]
Target Regulation	Up regulation
Pathway Response	Wnt signaling pathway			hsa04310
In-vitro Model	KLE	Endometrial adenocarcinoma	Homo sapiens	CVCL_1329
In-vitro Model	AN3-CA	Endometrial adenocarcinoma	Homo sapiens	CVCL_0028
In-vivo Model	Female SCID-Beige mice (6 weeks old) were purchased from Vitalriver. AN3CA cells with FTO overexpression or silencing or the appropriate controls (1 × 10⁶) were injected into the lower abdominal cavity of mice (n = 5 mice/group). After 4 weeks, the mice were sacrificed, and tumours were harvested, weighed and photographed.
Response Summary	This study found high expression of FTO in metastatic endometrial cancer and that this action promote both metastasis and invasion in vivo and in vitro. Mechanistically, FTO can catalyse demethylation modification in 3'UTR region of Homeobox protein Hox-B13 (HOXB13) mRNA, thereby abolishing m6A modification recognition with the YTHDF2 protein.

Interleukin enhancer-binding factor 3 (ILF3)

Target Gene

Brain cancer [ICD-11: 2A00]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[81]
Responsed Disease	Glioblastoma [ICD-11: 2A00.00]
Target Regulation	Up regulation
In-vitro Model	GBM1	Glioblastoma	Homo sapiens	CVCL_DG57
	GBM2	Glioblastoma	Homo sapiens	CVCL_DG58
	GBM3	Glioblastoma	Homo sapiens	CVCL_DG59
Response Summary	loss of m6A RNA methylation and increased translation in human glioblastoma cells as well as a role for miRNAs in the modulation of m6A RNA demethylation in genes that are most efficiently translated during glioma stem cells differentiation. Ectopic expression of the RRACH-binding miR-145 induces loss of m6A, formation of FTO/AGO1/Interleukin enhancer-binding factor 3 (ILF3)/miR-145 complexes on a clinically relevant tumor suppressor gene (CLIP3) and significant increase in its nascent translation.

Isocitrate dehydrogenase [NADP] cytoplasmic (IDH/IDH1)

Target Gene

Acute myeloid leukaemia [ICD-11: 2A60]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[82]
Responsed Disease	Acute myeloid leukaemia [ICD-11: 2A60]
Target Regulation	Down regulation
Cell Process	Glutamine metabolism
In-vitro Model	HEK293T	Normal	Homo sapiens	CVCL_0063
Response Summary	1) Isocitrate dehydrogenase [NADP] cytoplasmic (IDH/IDH1) mutant cells, likely via a D2-HG-mediated competitive inhibition of the Alpha-KG-dependent RNA demethylase FTO, display significantly elevated RNA methylation; 2) Deregulated RNA methylation should be considered part of the pathogenesis of IDH-mutant tumors, which alongside with the well-characterized DNA and histone disturbances defines a "hypermethylation triad"; 3) the effects of FTO expression on AML pathogenesis need to be interpreted in the context of IDH1/2 mutation since in this setting FTO activity is probably low, irrespective of its expression level.

Mammalian target of rapamycin complex 1 (mTORC1)

Target Gene

Gastric cancer [ICD-11: 2B72]

In total 3 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[19]
Responsed Disease	Gastric cancer [ICD-11: 2B72]
Responsed Drug	Cisplatin		Approved	Drug Info
Target Regulation	Down regulation
Pathway Response	mTOR signaling pathway			hsa04150
Cell Process	Cell apoptosis
In-vitro Model	AGS	Gastric adenocarcinoma	Homo sapiens	CVCL_0139
In-vitro Model	HGC-27	Gastric carcinoma	Homo sapiens	CVCL_1279
Response Summary	Omeprazole pretreatment could enhance the inhibitory effect of 5-Fu, DDP and TAX on gastric cancer cells. FTO inhibition induced by omeprazole enhanced the activation of Mammalian target of rapamycin complex 1 (mTORC1) signal pathway that inhibited the prosurvival autophagy so as to improve the antitumor efficiency of chemotherapeutic drugs on GC cells. Meanwhile, transcript level of DDIT3, which is an apoptosis-related tumor suppressor gene downstream of mTORC1, was regulated by omeprazole-induced FTO silence through an m6A-dependent mechanism. m6A modification and its eraser FTO plays a role in the improvement of chemosensitivity mediated by proton pump inhibitor omeprazole.
Experiment 2 Reporting the m6A-centered Disease Response of This Target Gene				[19]
Responsed Disease	Gastric cancer [ICD-11: 2B72]
Responsed Drug	Fluorouracil		Approved	Drug Info
Target Regulation	Down regulation
Pathway Response	mTOR signaling pathway			hsa04150
Cell Process	Cell apoptosis
In-vitro Model	AGS	Gastric adenocarcinoma	Homo sapiens	CVCL_0139
In-vitro Model	HGC-27	Gastric carcinoma	Homo sapiens	CVCL_1279
Response Summary	Omeprazole pretreatment could enhance the inhibitory effect of 5-Fu, DDP and TAX on gastric cancer cells. FTO inhibition induced by omeprazole enhanced the activation of Mammalian target of rapamycin complex 1 (mTORC1) signal pathway that inhibited the prosurvival autophagy so as to improve the antitumor efficiency of chemotherapeutic drugs on GC cells. Meanwhile, transcript level of DDIT3, which is an apoptosis-related tumor suppressor gene downstream of mTORC1, was regulated by omeprazole-induced FTO silence through an m6A-dependent mechanism. m6A modification and its eraser FTO plays a role in the improvement of chemosensitivity mediated by proton pump inhibitor omeprazole.
Experiment 3 Reporting the m6A-centered Disease Response of This Target Gene				[19]
Responsed Disease	Gastric cancer [ICD-11: 2B72]
Responsed Drug	Paclitaxel		Approved	Drug Info
Target Regulation	Down regulation
Pathway Response	mTOR signaling pathway			hsa04150
Cell Process	Cell apoptosis
In-vitro Model	AGS	Gastric adenocarcinoma	Homo sapiens	CVCL_0139
In-vitro Model	HGC-27	Gastric carcinoma	Homo sapiens	CVCL_1279
Response Summary	Omeprazole pretreatment could enhance the inhibitory effect of 5-Fu, DDP and TAX on gastric cancer cells. FTO inhibition induced by omeprazole enhanced the activation of Mammalian target of rapamycin complex 1 (mTORC1) signal pathway that inhibited the prosurvival autophagy so as to improve the antitumor efficiency of chemotherapeutic drugs on GC cells. Meanwhile, transcript level of DDIT3, which is an apoptosis-related tumor suppressor gene downstream of mTORC1, was regulated by omeprazole-induced FTO silence through an m6A-dependent mechanism. m6A modification and its eraser FTO plays a role in the improvement of chemosensitivity mediated by proton pump inhibitor omeprazole.

Mammalian target of rapamycin complex 2 (mTORC2)

Target Gene

Visual impairment [ICD-11: 9D90]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[83]
Responsed Disease	Vision impairment [ICD-11: 9D90]
In-vitro Model	HUVEC-C	Normal	Homo sapiens	CVCL_2959
In-vivo Model	After general anesthesia with an intraperitoneal injection of ketamine (80 mg/kg) and xylazine (4 mg/kg), topical application of 0.5% proparacaine ophthalmic solution was conducted. Three sutures (10-0 nylon) were placed intrastromally between the limbus and corneal center at the 4, 8, and 12 o'clock positions. Topical norfloxacin was applied after surgery.
Response Summary	FTO regulates pathological ocular angiogenesis by controlling endothelial cell function in an m6A-YTHDF2-dependent manner. Pathological ocular angiogenesis commonly results in visual impairment or even blindness.

Metastasis-associated protein MTA1 (MTA1)

Target Gene

Colorectal cancer [ICD-11: 2B91]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[84]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulation	Down regulation
Pathway Response	mRNA surveillance pathway			hsa03015
Pathway Response	RNA degradation			hsa03018
Cell Process	RNA stability
In-vitro Model	SW620	Colon adenocarcinoma	Homo sapiens	CVCL_0547
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
	RKO	Colon carcinoma	Homo sapiens	CVCL_0504
	LS174T	Colon adenocarcinoma	Homo sapiens	CVCL_1384
	LoVo	Colon adenocarcinoma	Homo sapiens	CVCL_0399
	HT29	Colon cancer	Mus musculus	CVCL_A8EZ
	HCT 8	Colon adenocarcinoma	Homo sapiens	CVCL_2478
	HCT 15	Colon adenocarcinoma	Homo sapiens	CVCL_0292
	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	DLD-1	Colon adenocarcinoma	Homo sapiens	CVCL_0248
	CW-2	Colon adenocarcinoma	Homo sapiens	CVCL_1151
In-vivo Model	FTO-overexpressing and control cells (2 × 10⁶ suspended in 100 ul PBS) were subcutaneously injected into each mouse.
Response Summary	FTO inhibited CRC metastasis both in vitro and in vivo. FTO exerted a tumor suppressive role by inhibiting Metastasis-associated protein MTA1 (MTA1) expression in an m6A-dependent manner. Methylated MTA1 transcripts were recognized by an m6A "reader", insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2), which then stabilized its mRNA.

Nuclear factor erythroid 2-related factor 2 (NFE2L2)

Target Gene

Male reproductive disorders [ICD-11: VV5Z]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[85]
Responsed Disease	Male reproductive disorders [ICD-11: VV5Z]
Target Regulation	Up regulation
Cell Process	Oxidative stress
	Cell apoptosis
In-vivo Model	Exposed Sprague-Dawley rats to 0, 250, and 500 mg DEHP per kg body weight per day at the prepuberty stage from postnatal day 22 (PND 22) to PND 35 by oral gavage.
Response Summary	DEHP worsened testicular histology, decreased testosterone concentrations, downregulated expression of spermatogenesis inducers, enhanced oxidative stress, inhibited the Nuclear factor erythroid 2-related factor 2 (NFE2L2)-mediated antioxidant pathway, and increased apoptosis in testes. DEHP is a common environmental endocrine disrupting chemical that induces male reproductive disorders. Additionally, DEHP increased global levels of m6A RNA modification and altered the expression of two important RNA methylation modulator genes, FTO and YTHDC2.

Poly [ADP-ribose] polymerase 1 (PARP1)

Target Gene

Colorectal cancer [ICD-11: 2B91]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[77]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulation	Up regulation
Pathway Response	Glutathione metabolism			hsa00480
In-vitro Model	LoVo	Colon adenocarcinoma	Homo sapiens	CVCL_0399
	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	HCT 8	Colon adenocarcinoma	Homo sapiens	CVCL_2478
	SW620	Colon adenocarcinoma	Homo sapiens	CVCL_0547
In-vivo Model	For CDX model, nude mice (female, 4-6-week-old) were subcutaneously injected with 5 × 10⁶ HCT116 cells on the both flank. For PDX model, the patient tumors were divided into small pieces and then inoculated on both flank of nude mice. For knockdown FTO mice model, FTO mice model, two weeks after inoculation, the shFTO#3 lenti-virus injected into the tumor for three consecutive days. For combined medication mice model, intraperitoneal injection of Rhein and Olaparib was started one week after inoculation
Response Summary	Targeting FTO significantly suppresses cancer cell growth and enhances chemotherapy sensitivity, which not only mediating the balance of intracellular ROS by regulating G6PD expression, but also maintaining genome instability by regulating Poly [ADP-ribose] polymerase 1 (PARP1) expression. These findings shed light on new molecular mechanisms of CRC development and treatments mediated by m6A modification.

Programmed cell death 1 (PD-1)

Target Gene

Melanoma [ICD-11: 2C30]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[7]
Responsed Disease	Melanoma [ICD-11: 2C30]
Responsed Drug	PMID31239444-anti-PD1 antibody		Investigative	Drug Info
Target Regulation	Up regulation
Pathway Response	PD-L1 expression and PD-1 checkpoint pathway in cancer			hsa05235
Cell Process	mRNA decay
In-vitro Model	B16-F10	Mouse melanoma	Mus musculus	CVCL_0159
	CHL-1	Melanoma	Homo sapiens	CVCL_1122
	624-mel	Melanoma	Homo sapiens	CVCL_8054
	NHEM (Normal Human Epidermal Melanocytes)
	SK-MEL-30	Cutaneous melanoma	Homo sapiens	CVCL_0039
	WM115	Melanoma	Homo sapiens	CVCL_0040
	WM35	Melanoma	Homo sapiens	CVCL_0580
	WM3670	Melanoma	Homo sapiens	CVCL_6799
	WM793	Melanoma	Homo sapiens	CVCL_8787
In-vivo Model	When the tumors reached a volume of 80-100 mm³, mice were treated with anti-PD-1 or isotype control antibody (200 ug/mouse) by i.p. injection, every other day for three times. For IFNγ blockade treatment, C57BL/6 mice were treated with anti-IFNγ antibody or isotype control IgG (250 ug/mouse) every other day after tumor cell inoculation.
Response Summary	These findings demonstrate a crucial role of FTO as an m6A demethylase in promoting melanoma tumorigenesis and anti-PD-1 resistance, and suggest that the combination of FTO inhibition with anti-PD-1 blockade reduces the resistance to immunotherapy in melanoma. Knockdown of FTO increases m6A methylation in the critical protumorigenic melanoma cell-intrinsic genes including Programmed cell death 1 (PD-1) (PDCD1), CXCR4, and SOX10, leading to increased RNA decay through the m6A reader YTHDF2.

Protein argonaute-1 (AGO1)

Target Gene

Brain cancer [ICD-11: 2A00]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[81]
Responsed Disease	Glioblastoma [ICD-11: 2A00.00]
Target Regulation	Up regulation
In-vitro Model	GBM1	Glioblastoma	Homo sapiens	CVCL_DG57
	GBM2	Glioblastoma	Homo sapiens	CVCL_DG58
	GBM3	Glioblastoma	Homo sapiens	CVCL_DG59
Response Summary	loss of m6A RNA methylation and increased translation in human glioblastoma cells as well as a role for miRNAs in the modulation of m6A RNA demethylation in genes that are most efficiently translated during glioma stem cells differentiation. Ectopic expression of the RRACH-binding miR-145 induces loss of m6A, formation of FTO/Protein argonaute-1 (AGO1)/ILF3/miR-145 complexes on a clinically relevant tumor suppressor gene (CLIP3) and significant increase in its nascent translation.

Protein CBFA2T1 (RUNX1T1)

Target Gene

Obesity [ICD-11: 5B81]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[86]
Responsed Disease	Obesity [ICD-11: 5B81]
Target Regulation	Down regulation
Cell Process	adipogenesis
	Spliceosome (hsa03040)
In-vitro Model	3T3-L1	Normal	Mus musculus	CVCL_0123
Response Summary	FTO-dependent m7A demethylation functions as a novel regulatory mechanism of RNA processing and plays a critical role in the regulation of adipogenesis and obesity. FTO-dependent regulatory role of m6A and SRSF2 in mRNA splicing and adipocyte differentiation. FTO controls exonic splicing of adipogenic regulatory factor Protein CBFA2T1 (RUNX1T1) by regulating m6A levels around splice sites and thereby modulates differentiation.

Protein kinase C-binding protein NELL2 (NELL2)

Target Gene

Lung cancer [ICD-11: 2C25]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[87]
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulation	Up regulation
Cell Process	Cell viability
	Cell migration
	Cell invasion
In-vitro Model	NCI-H460	Lung large cell carcinoma	Homo sapiens	CVCL_0459
	NCI-H23	Lung adenocarcinoma	Homo sapiens	CVCL_1547
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	16HBE14o-	Normal	Homo sapiens	CVCL_0112
In-vivo Model	The nude mice were maintained under pathogen-free conditions and kept under timed lighting conditions mandated by the committee with food and water provided ad libitum. For xenograft experiments, nude mice were injected subcutaneously with 5 × 10⁶ cells resuspended in 0.1 mL PBS. When a tumor was palpable, it was measured every 3 days.
Response Summary	FTO upregulated the expression of E2F1 by inhibiting the m6A modification of E2F1. The FTO/E2F1/Protein kinase C-binding protein NELL2 (NELL2) axis modulated NSCLC cell viability, migration, and invasion in vitro as well as affected NSCLC tumor growth and metastasis in vivo.

Receptor tyrosine-protein kinase erbB-2 (ERBB2)

Target Gene

Oral cavity/oesophagus/stomach in situ carcinoma [ICD-11: 2E60]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[88]
Responsed Disease	Esophageal squamous cell carcinoma [ICD-11: 2B70.1]
Target Regulation	Up regulation
Cell Process	Cell proliferation
	Cell migration
	Cell invasion
In-vitro Model	KYSE-450	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1353
	KYSE-30	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1351
	KYSE-180	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1349
	KYSE-150	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1348
	KYSE-140	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1347
In-vivo Model	For the subcutaneous transplantation model, sh-control, sh-FTO, NC-OE and ERBB2-OE KYSE150 stable cells (6 × 10⁶ per mouse, n = 3 for each group) were diluted to 100 uL PBS + 100 uL Matrigel (BD) and subcutaneously injected to two points in the middle and upper groin of immunodeficient mice to study tumor growth. When the tumor volume reached ~ 1000 mm³ in each group, the nude mice were killed, and the tumors were excised and weighed for histology and further study. The tumor volume was calculated by the formula V = 1/2 × large diameter × (small diameter)2. For a model of lung metastasis in vivo, nude mice were injected with 100 uL WT (wide type), sh-FTO, ERBB2-OE and sh-FTO+ERBB2-OE KYSE150 stable cells (1 × 10⁶ cells per mouse, n = 3 for each group) through tail vein, respectively. Six weeks after injection, the mice were killed and analyzed for metastatic lung tumors.
Response Summary	Knockdown of FTO drastically suppressed the proliferation, migration, and invasion of ESCC cells,and Receptor tyrosine-protein kinase erbB-2 (ERBB2) is the target of FTO, which acts in concert in ESCC tumorigenesis and metastasis.

Retinoic acid receptor alpha (RARA)

Target Gene

Acute myeloid leukaemia [ICD-11: 2A60]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[2]
Responsed Disease	Acute myeloid leukaemia [ICD-11: 2A60]
Responsed Drug	Tretinoin		Approved	Drug Info
Target Regulation	Down regulation
Cell Process	RNA stability
Cell Process	RNA degradation (hsa03018)
In-vitro Model	K-562	Chronic myelogenous leukemia	Homo sapiens	CVCL_0004
	KOCL-48	Childhood acute monocytic leukemia	Homo sapiens	CVCL_6867
	Mono-Mac-6	Adult acute monocytic leukemia	Homo sapiens	CVCL_1426
Response Summary	FTO enhances leukemic oncogene-mediated cell transformation and leukemogenesis, and inhibits all-trans-retinoic acid (ATRA)-induced AML cell differentiation, through regulating expression of targets such as ASB2 and Retinoic acid receptor alpha (RARA) by reducing m6A levels in these mRNA transcripts.

Serine/threonine-protein kinase mTOR (MTOR)

Target Gene

Colorectal cancer [ICD-11: 2B91]

In total 6 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[12]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Responsed Drug	Asparagine inhibitor		Approved	Drug Info
Pathway Response	mTOR signaling pathway			hsa04150
	Autophagy			hsa04140
Cell Process	RNA decay
	Cell growth and death
	Cell autophagy
In-vitro Model	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
Response Summary	In colorectal cancer, Glutaminolysis inhibition upregulated ATF4 expression in an m6A-dependent manner to activate pro-survival autophagy through transcriptional activation of the mTOR inhibitor DDIT4. Determined the relationship between FTO alpha-ketoglutarate dependent dioxygenase (FTO), YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), and ATF4. ATF4 transcriptionally upregulated DDIT4 to suppress Serine/threonine-protein kinase mTOR (MTOR), which induced pro-survival autophagy during glutaminolysis inhibition.
Experiment 2 Reporting the m6A-centered Disease Response of This Target Gene				[12]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Responsed Drug	Chloroquine		Approved	Drug Info
Pathway Response	mTOR signaling pathway			hsa04150
	Autophagy			hsa04140
Cell Process	RNA decay
	Cell growth and death
	Cell autophagy
In-vitro Model	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
Response Summary	In colorectal cancer, Glutaminolysis inhibition upregulated ATF4 expression in an m6A-dependent manner to activate pro-survival autophagy through transcriptional activation of the mTOR inhibitor DDIT4. Determined the relationship between FTO alpha-ketoglutarate dependent dioxygenase (FTO), YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), and ATF4. ATF4 transcriptionally upregulated DDIT4 to suppress Serine/threonine-protein kinase mTOR (MTOR), which induced pro-survival autophagy during glutaminolysis inhibition.
Experiment 3 Reporting the m6A-centered Disease Response of This Target Gene				[12]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Responsed Drug	Meclofenamate sodium		Approved	Drug Info
Pathway Response	mTOR signaling pathway			hsa04150
	Autophagy			hsa04140
Cell Process	RNA decay
	Cell growth and death
	Cell autophagy
In-vitro Model	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
Response Summary	In colorectal cancer, Glutaminolysis inhibition upregulated ATF4 expression in an m6A-dependent manner to activate pro-survival autophagy through transcriptional activation of the mTOR inhibitor DDIT4. Determined the relationship between FTO alpha-ketoglutarate dependent dioxygenase (FTO), YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), and ATF4. Serine/threonine-protein kinase mTOR (MTOR) transcriptionally upregulated DDIT4 to suppress mTOR, which induced pro-survival autophagy during glutaminolysis inhibition.
Experiment 4 Reporting the m6A-centered Disease Response of This Target Gene				[12]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Responsed Drug	Rapamycin		Approved	Drug Info
Pathway Response	mTOR signaling pathway			hsa04150
	Autophagy			hsa04140
Cell Process	RNA decay
	Cell growth and death
	Cell autophagy
In-vitro Model	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
Response Summary	In colorectal cancer, Glutaminolysis inhibition upregulated ATF4 expression in an m6A-dependent manner to activate pro-survival autophagy through transcriptional activation of the mTOR inhibitor DDIT4. Determined the relationship between FTO alpha-ketoglutarate dependent dioxygenase (FTO), YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), and ATF4. Serine/threonine-protein kinase mTOR (MTOR) transcriptionally upregulated DDIT4 to suppress mTOR, which induced pro-survival autophagy during glutaminolysis inhibition.
Experiment 5 Reporting the m6A-centered Disease Response of This Target Gene				[12]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Responsed Drug	CB-839		Phase 2	Drug Info
Pathway Response	mTOR signaling pathway			hsa04150
	Autophagy			hsa04140
Cell Process	RNA decay
	Cell growth and death
	Cell autophagy
In-vitro Model	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
Response Summary	In colorectal cancer, Glutaminolysis inhibition upregulated ATF4 expression in an m6A-dependent manner to activate pro-survival autophagy through transcriptional activation of the mTOR inhibitor DDIT4. Determined the relationship between FTO alpha-ketoglutarate dependent dioxygenase (FTO), YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), and ATF4. Serine/threonine-protein kinase mTOR (MTOR) transcriptionally upregulated DDIT4 to suppress mTOR, which induced pro-survival autophagy during glutaminolysis inhibition.
Experiment 6 Reporting the m6A-centered Disease Response of This Target Gene				[12]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Responsed Drug	GLS-IN-968		Investigative	Drug Info
Pathway Response	mTOR signaling pathway			hsa04150
	Autophagy			hsa04140
Cell Process	RNA decay
	Cell growth and death
	Cell autophagy
In-vitro Model	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
Response Summary	In colorectal cancer, Glutaminolysis inhibition upregulated ATF4 expression in an m6A-dependent manner to activate pro-survival autophagy through transcriptional activation of the mTOR inhibitor DDIT4. Determined the relationship between FTO alpha-ketoglutarate dependent dioxygenase (FTO), YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), and ATF4. ATF4 transcriptionally upregulated DDIT4 to suppress Serine/threonine-protein kinase mTOR (MTOR), which induced pro-survival autophagy during glutaminolysis inhibition.

Signal transducer and activator of transcription 3 (STAT3)

Target Gene

Breast cancer [ICD-11: 2C60]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[89]
Responsed Disease	Breast cancer [ICD-11: 2C60]
Responsed Drug	Doxil		Approved	Drug Info
In-vitro Model	MDA-MB-231	Breast adenocarcinoma	Homo sapiens	CVCL_0062
	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
	Hs 578T	Invasive breast carcinoma	Homo sapiens	CVCL_0332
Response Summary	Decreased doxorubicin resistance by Signal transducer and activator of transcription 3 (STAT3) knockdown was abolished by FTO overexpression and decreased doxorubicin sensitivity by STAT3 overexpression was reversed by FTO knockdown, indicating that FTO was implicated in STAT3-mediated doxorubicin resistance and impairment of doxorubicin sensitivity of BC cells.

Splicing factor, proline- and glutamine-rich (SFPQ)

Target Gene

Bladder cancer [ICD-11: 2C94]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[27]
Responsed Disease	Bladder cancer [ICD-11: 2C94]
Pathway Response	Notch signaling pathway			hsa04330
Cell Process	Cell proliferation
	Cell invasion
	Cell apoptosis
In-vitro Model	HT-1197	Recurrent bladder carcinoma	Homo sapiens	CVCL_1291
	HT-1376	Bladder carcinoma	Homo sapiens	CVCL_1292
In-vivo Model	BALB/cnu/nu mice (4-5 weeks old) were used for the xenograft experiment. The mice were randomly divided into 2 groups (n = 6 for each group) and injected with 5 × 10⁶ HT-1197 cells in control group or FTO plasmid group, respectively.
Response Summary	In bladder cancer, the changes in m6A methylation level mainly appeared at 5' untranslated region (5' UTR) of MALAT1 and NOTCH1 transcripts, and at 3' UTR of CSNK2A2 and ITGA6 transcripts, responding to the overexpression of FTO. Splicing factor, proline- and glutamine-rich (SFPQ) could influence the FTO-mediated m6A RNA demethylation, eventually affecting the gene expression.

SRSF protein kinase 2 (SRPK2)

Target Gene

Obesity [ICD-11: 5B81]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[86]
Responsed Disease	Obesity [ICD-11: 5B81]
Target Regulation	Down regulation
Pathway Response	Spliceosome			hsa03040
Cell Process	adipogenesis
In-vitro Model	3T3-L1	Normal	Mus musculus	CVCL_0123
Response Summary	FTO-dependent m7A demethylation functions as a novel regulatory mechanism of RNA processing and plays a critical role in the regulation of adipogenesis and obesity. FTO-dependent regulatory role of m6A and SRSF protein kinase 2 (SRPK2) in mRNA splicing and adipocyte differentiation. FTO controls exonic splicing of adipogenic regulatory factor RUNX1T1 by regulating m6A levels around splice sites and thereby modulates differentiation.

Suppressor of cytokine signaling 1 (SOCS1)

Target Gene

Chronic kidney disease [ICD-11: GB61]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[90]
Responsed Disease	Chronic kidney disease [ICD-11: GB61.Z]
Target Regulation	Up regulation
Pathway Response	JAK-STAT signaling pathway			hsa04630
In-vitro Model	HEK293T	Normal	Homo sapiens	CVCL_0063
	hMC	Normal	Homo sapiens	CVCL_9Q61
	HK-2 [Human kidney]	Normal	Homo sapiens	CVCL_0302
In-vivo Model	FTO over-expression db/db mice were generated through injecting the tail vein with Fto-overexpression lentivirus at 12 weeks.
Response Summary	Mechanistically, the FTO/Suppressor of cytokine signaling 1 (SOCS1)/JAK-STAT axis promotes diabetic kidney disease(DKD) pathogenesis via promoting inflammation. Moreover, FTO expression is significantly decreased in DKD, and overexpression of FTO can dramatically alleviate kidney inflammation.

Transcription factor E2F1 (E2F1)

Target Gene

Lung cancer [ICD-11: 2C25]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[37]
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Pathway Response	p53 signaling pathway	hsa04115
	Central carbon metabolism in cancer	hsa05230
	PD-L1 expression and PD-1 checkpoint pathway in cancer	hsa05235
Response Summary	This study revealed that m6A methylation is closely related to the poor prognosis of non-small cell lung cancer patients via interference with the TIME, which suggests that m6A plays a role in optimizing individualized immunotherapy management and improving prognosis. The expression levels of METTL3, FTO and YTHDF1 in non-small cell lung cancer were changed. Patients in Cluster 1 had lower immunoscores, higher programmed death-ligand 1 (PD-L1) expression, and shorter overall survival compared to patients in Cluster 2. The hallmarks of the Myelocytomatosis viral oncogene (MYC) targets, Transcription factor E2F1 (E2F1) targets were significantly enriched.

Cervical cancer [ICD-11: 2C77]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[38]
Responsed Disease	Cervical cancer [ICD-11: 2C77]
Target Regulation	Up regulation
Cell Process	Cell proliferation and migration
In-vitro Model	HeLa	Endocervical adenocarcinoma	Homo sapiens	CVCL_0030
In-vitro Model	SiHa	Cervical squamous cell carcinoma	Homo sapiens	CVCL_0032
Response Summary	FTO interacts with transcripts of Transcription factor E2F1 (E2F1) and Myc, inhibition of FTO significantly impairs the translation efficiency of E2F1 and Myc.FTO plays important oncogenic role in regulating cervical cancer cells' proliferation.

Ubiquitin carboxyl-terminal hydrolase 7 (USP7)

Target Gene

Lung cancer [ICD-11: 2C25]

In total 2 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[91]
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Responsed Drug	P22077		Investigative	Drug Info
Target Regulation	Up regulation
Cell Process	Ubiquitination degradation
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	NCI-H522	Lung adenocarcinoma	Homo sapiens	CVCL_1567
	HSAEC (Human small airway epithelial cells)
	RERF-LC-A1	Lung squamous cell carcinoma	Homo sapiens	CVCL_4402
	NCI-H1882	Lung small cell carcinoma	Homo sapiens	CVCL_1504
	NCl-H466 (Human lung cancer cell line)
In-vivo Model	Equal numbers of A549 cells expressing either control or shFTO were injected subcutaneously, within 30 min of harvesting, over the right and left flanks in male nu/nu mice between 4 and 6 weeks of age.
Response Summary	The m6A demethylase FTO promotes the growth of Non-small cell lung cancer cells by increasing the expression of USP7.Genetic knockdown or pharmacological inhibition (P5091 or P22027) of Ubiquitin carboxyl-terminal hydrolase 7 (USP7) reduced the proliferation rate of lung cancer cells and decreased the capacity of colony formation of lung cancer cells in vitro, whereas lung cancer cells growth inhibition by FTO knockdown is restored by overexertion of USP7.
Experiment 2 Reporting the m6A-centered Disease Response of This Target Gene				[91]
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Responsed Drug	P5091		Investigative	Drug Info
Target Regulation	Up regulation
Cell Process	Ubiquitination degradation
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	NCI-H522	Lung adenocarcinoma	Homo sapiens	CVCL_1567
	HSAEC (Human small airway epithelial cells)
	RERF-LC-A1	Lung squamous cell carcinoma	Homo sapiens	CVCL_4402
	NCI-H1882	Lung small cell carcinoma	Homo sapiens	CVCL_1504
	NCl-H466 (Human lung cancer cell line)
In-vivo Model	Equal numbers of A549 cells expressing either control or shFTO were injected subcutaneously, within 30 min of harvesting, over the right and left flanks in male nu/nu mice between 4 and 6 weeks of age.
Response Summary	The m6A demethylase FTO promotes the growth of Non-small cell lung cancer cells by increasing the expression of USP7.Genetic knockdown or pharmacological inhibition (P5091 or P22027) of Ubiquitin carboxyl-terminal hydrolase 7 (USP7) reduced the proliferation rate of lung cancer cells and decreased the capacity of colony formation of lung cancer cells in vitro, whereas lung cancer cells growth inhibition by FTO knockdown is restored by overexertion of USP7.

Deleted in lymphocytic leukemia 2 (DLEU2/LINC00022)

Target Gene

Oral cavity/oesophagus/stomach in situ carcinoma [ICD-11: 2E60]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[16]
Responsed Disease	Esophageal squamous cell carcinoma [ICD-11: 2B70.1]
Target Regulation	Down regulation
Pathway Response	Cell cycle			hsa04110
Pathway Response	Ubiquitin mediated proteolysis			hsa04120
Cell Process	Ubiquitination degradation
	Cell apoptosis
	Decreased G0/G1 phase
In-vitro Model	HET-1A	Normal	Homo sapiens	CVCL_3702
	KYSE-150	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1348
	KYSE-450	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1353
	KYSE-70	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1356
	TE-1	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1759
In-vivo Model	The number of cells inoculated in each mouse was 4 × 10⁶, 1 × 10⁶, 2 × 10⁶ and 1 × 10⁶, respectively.
Response Summary	The elevated FTO in esophageal squamous cell carcinoma decreased m6A methylation of Deleted in lymphocytic leukemia 2 (DLEU2/LINC00022) transcript, leading to the inhibition of LINC00022 decay via the m6A reader YTHDF2.

HOXC13 antisense RNA (HOXC13-AS)

Target Gene

Cervical cancer [ICD-11: 2C77]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[92]
Responsed Disease	Cervical cancer [ICD-11: 2C77]
Target Regulation	Up regulation
Pathway Response	Wnt signaling pathway			hsa04310
Cell Process	Cell proliferation
	Cell invasion
	Epithelial-mesenchymal transition
In-vitro Model	C-33 A	Cervical squamous cell carcinoma	Homo sapiens	CVCL_1094
	C-4-I	Cervical squamous cell carcinoma	Homo sapiens	CVCL_2253
	Ect1/E6E7	Normal	Homo sapiens	CVCL_3679
	HeLa	Endocervical adenocarcinoma	Homo sapiens	CVCL_0030
	SiHa	Cervical squamous cell carcinoma	Homo sapiens	CVCL_0032
Response Summary	FTO-stabilized HOXC13 antisense RNA (HOXC13-AS) epigenetically up-regulated FZD6 and activated Wnt/beta-catenin signaling to drive cervical cancer proliferation, invasion, and EMT, suggesting HOXC13-AS as a potential target for cervical cancer treatment.

Myosin heavy chain associated RNA transcript (MHRT)

Target Gene

Congestive heart failure [ICD-11: BD10]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[93]
Responsed Disease	Congestive heart failure [ICD-11: BD10]
Target Regulation	Up regulation
Cell Process	Cell apoptosis
In-vitro Model	Mouse myocardial cell line (Isolated from heart tissue)
In-vivo Model	The mice were housed under standardized conditions and received normal diet. The mice were randomly divided into 5 groups (n = 6/each group): (1) Control group: normal mice served as control; (2) TAC-HF group: mice were subjected to transverse aortic constriction (TAC) to establish HF mouse model; (3) Sham group: sham-operated mice were subjected the same surgery without the placement of a ligature; (4) Doxorubicin-HF group: mice were intraperitoneally injected with doxorubicin to construct HF mouse model; and (5) PBS: mice were intraperitoneally injected with equal PBS as control.
Response Summary	FTO overexpression inhibits H/R-indcued apoptosis in myocardial cells by regulating m6A modification of Myosin heavy chain associated RNA transcript (MHRT). FTO is a target gene for heart failure treatment.

Pvt1 oncogene (PVT1)

Target Gene

Kidney failure [ICD-11: GB6Z]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[65]
Responsed Disease	Kidney failure [ICD-11: GB6Z]
Target Regulation	Up regulation
In-vitro Model	NIT-1	Insulin tumor	Mus musculus	CVCL_3561
Response Summary	m6A modification is co-regulated by METTL3 and FTO in cadmium-treated cells. LncRNA-MALAT1, Pvt1 oncogene (PVT1) and m6A modification could be key nodes for cadmium-induced oxidative damage, and highlight their importance as promising preventive and therapeutic targets in cadmium toxicity.

microRNA 145 (MIR145)

Target Gene

Brain cancer [ICD-11: 2A00]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[81]
Responsed Disease	Glioblastoma [ICD-11: 2A00.00]
Target Regulation	Up regulation
In-vitro Model	GBM1	Glioblastoma	Homo sapiens	CVCL_DG57
	GBM2	Glioblastoma	Homo sapiens	CVCL_DG58
	GBM3	Glioblastoma	Homo sapiens	CVCL_DG59
Response Summary	loss of m6A RNA methylation and increased translation in human glioblastoma cells as well as a role for miRNAs in the modulation of m6A RNA demethylation in genes that are most efficiently translated during glioma stem cells differentiation. Ectopic expression of the RRACH-binding miR-145 induces loss of m6A, formation of FTO/AGO1/ILF3/microRNA 145 (MIR145) complexes on a clinically relevant tumor suppressor gene (CLIP3) and significant increase in its nascent translation.

microRNA 155 (MIR155)

Target Gene

Brain cancer [ICD-11: 2A00]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[94]
Responsed Disease	Glioma [ICD-11: 2A00.0]
Responsed Drug	Temozolomide		Approved	Drug Info
In-vitro Model	A-172	Glioblastoma	Homo sapiens	CVCL_0131
	HEK293T	Normal	Homo sapiens	CVCL_0063
	U251 (Fibroblasts or fibroblast like cells)
	U87 (A primary glioblastoma cell line)
In-vivo Model	Previously prepared U87 cells (5 × 10⁶ cells, 60 uL) stably infected with miRNA were injected subcutaneously in the right flank of the mice, whereas control U87 cells infected with empty vector were injected in the left flank.
Response Summary	FTO Inhibition Enhances the Antitumor Effect of Temozolomide by Targeting MYC-microRNA 155 (MIR155)/miR-23a Cluster-MXI1 Feedback Circuit in Glioma.

microRNA 23a (MIR23A)

Target Gene

Brain cancer [ICD-11: 2A00]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[94]
Responsed Disease	Glioma [ICD-11: 2A00.0]
Responsed Drug	Temozolomide		Approved	Drug Info
In-vitro Model	A-172	Glioblastoma	Homo sapiens	CVCL_0131
	HEK293T	Normal	Homo sapiens	CVCL_0063
	U251 (Fibroblasts or fibroblast like cells)
	U87 (A primary glioblastoma cell line)
In-vivo Model	Previously prepared U87 cells (5 × 10⁶ cells, 60 uL) stably infected with miRNA were injected subcutaneously in the right flank of the mice, whereas control U87 cells infected with empty vector were injected in the left flank.
Response Summary	FTO Inhibition Enhances the Antitumor Effect of Temozolomide by Targeting MYC-miR-155/microRNA 23a (MIR23A) Cluster-MXI1 Feedback Circuit in Glioma.

microRNA 576 (MIR576)

Target Gene

Bladder cancer [ICD-11: 2C94]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[70]
Responsed Disease	Bladder cancer [ICD-11: 2C94]
Target Regulation	Up regulation
Cell Process	Cell proliferation
	Cell migration
	Cell invasion
In-vitro Model	5637	Bladder carcinoma	Homo sapiens	CVCL_0126
	T24	Bladder carcinoma	Homo sapiens	CVCL_0554
	UM-UC-3	Bladder carcinoma	Homo sapiens	CVCL_1783
In-vivo Model	Approximately 1 × 10⁷ stably transfected T24 cells were subcutaneously injected into BALB/c nude mice. The length (L) and width (W) of the tumours were measured weekly using callipers, while their volume was calculated using the equation: V = (L × W2)/2. After 4 weeks of injections, the mice were euthanised, and the tumour tissues were removed and weighed.
Response Summary	FTO promoted bladder cancer cell proliferation, migration and invasion via the FTO/microRNA 576 (MIR576)/CDK6 pathways in an m6A-dependent manner.

hsa-miR-129-5p

Target Gene

Malignant mixed epithelial mesenchymal tumour [ICD-11: 2B5D]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[62]
Responsed Disease	Malignant mixed epithelial mesenchymal tumour of ovary [ICD-11: 2B5D.0]
Pathway Response	Autophagy			hsa04140
Cell Process	Cell autophagy
In-vitro Model	SK-OV-3	Ovarian serous cystadenocarcinoma	Homo sapiens	CVCL_0532
In-vivo Model	The SKOV3 ovarian cancer cell line was transfected with LV2-1 or LV2-NC. Thereafter, BALB/c nude mice (6-week old) were intraperitoneally injected with SKOV3 cells. The mice were killed after 5 weeks, and the number of ascites was determined.
Response Summary	CircRAB11FIP1 promoted autophagy flux of ovarian cancer through DSC1 and hsa-miR-129-5p. CircRAB11FIP1 can serve as the possible marker for EOC diagnosis and treatment. CircRAB11FIP1 regulated the mechanism of autophagy through m6A modification and direct binding to mRNA. CircRAB11FIP1 bound to the mRNA of FTO and promoted its expression. CircRAB11FIP1 directly bound to miR-129 and regulated its targets ATG7 and ATG14. CircRAB11FIP1 bound to desmocollin 1to facilitate its interaction with ATG101. CircRAB11FIP1 mediated mRNA expression levels of ATG5 and ATG7 depending on m6A.

hsa-miR-181b-3p

Target Gene

Breast cancer [ICD-11: 2C60]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[1]
Responsed Disease	Breast cancer [ICD-11: 2C60]
Target Regulation	Down regulation
Cell Process	Cell invasion and migration
In-vitro Model	T-47D	Invasive breast carcinoma	Homo sapiens	CVCL_0553
	SK-BR-3	Breast adenocarcinoma	Homo sapiens	CVCL_0033
	MDA-MB-453	Breast adenocarcinoma	Homo sapiens	CVCL_0418
	MDA-MB-231	Breast adenocarcinoma	Homo sapiens	CVCL_0062
	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
	MCF-10A	Normal	Homo sapiens	CVCL_0598
	BT-549	Invasive breast carcinoma	Homo sapiens	CVCL_1092
	BT-474	Invasive breast carcinoma	Homo sapiens	CVCL_0179
Response Summary	FTO up-regulated ARL5B by inhibiting hsa-miR-181b-3p. The carcinogenic activity of FTO in promoting the invasion and migration of breast cancer cells via the FTO/miR-181b-3p/ARL5B signaling pathway.

hsa-miR-5581-3p

Target Gene

Bladder cancer [ICD-11: 2C94]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[95]
Responsed Disease	Bladder cancer [ICD-11: 2C94]
Cell Process	Cell migration
Cell Process	cell proliferation
In-vitro Model	UM-UC-3	Bladder carcinoma	Homo sapiens	CVCL_1783
	T24	Bladder carcinoma	Homo sapiens	CVCL_0554
	SV-HUC-1	Normal	Homo sapiens	CVCL_3798
	HEK293T	Normal	Homo sapiens	CVCL_0063
In-vivo Model	Four-week-old male BALB/c nude mice were used for animal experiments. UM-UC3 cells (2×10⁶ cells per mouse) stably overexpressing miR-5581-3p and NC were injected into the mice to establish the subcutaneous implantation model. Tumor size was measured by a caliper every week, and tumor volume was calculated by the formula: V = (width2×length×0.52). As for the tumor metastasis model, UM-UC3 cells (1×10⁶ cells per mouse) were injected into each mouse via the tail vein. The subcutaneous implantation model used 8 nude mice, whereas the tumor metastasis model used 10 nude mice. Assessment of tumor size and observation of metastasis tumors were done via intraperitoneal inoculation with 15mg/mL, XenoLight D-luciferin Potassium Salt (100 uL; PerkinElmer) with the IVIS Spectrum animal imaging Platform (PerkinElmer) in every mouse. Eventually, mice were sacrificed for tumors and metastases.
Response Summary	FTO proved as an N6-methyladenosine (m6A) demethylase in decreasing m6A modification was confirmed to regulate the migration and proliferation in Bca, overexpressing hsa-miR-5581-3p partially rescued the effects of the overexpressing SMAD3 and FTO in BCa cells.

hsa_circ_0005630 (circRAB11FIP1)

Target Gene

Malignant mixed epithelial mesenchymal tumour [ICD-11: 2B5D]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[62]
Responsed Disease	Malignant mixed epithelial mesenchymal tumour of ovary [ICD-11: 2B5D.0]
Target Regulation	Up regulation
Pathway Response	Autophagy			hsa04140
Cell Process	Cell autophagy
In-vitro Model	SK-OV-3	Ovarian serous cystadenocarcinoma	Homo sapiens	CVCL_0532
In-vivo Model	The SKOV3 ovarian cancer cell line was transfected with LV2-1 or LV2-NC. Thereafter, BALB/c nude mice (6-week old) were intraperitoneally injected with SKOV3 cells. The mice were killed after 5 weeks, and the number of ascites was determined.
Response Summary	hsa_circ_0005630 (circRAB11FIP1) promoted autophagy flux of ovarian cancer through DSC1 and miR-129. CircRAB11FIP1 can serve as the possible marker for EOC diagnosis and treatment. CircRAB11FIP1 regulated the mechanism of autophagy through m6A modification and direct binding to mRNA. CircRAB11FIP1 bound to the mRNA of FTO and promoted its expression. CircRAB11FIP1 directly bound to miR-129 and regulated its targets ATG7 and ATG14. CircRAB11FIP1 bound to desmocollin 1to facilitate its interaction with ATG101. CircRAB11FIP1 mediated mRNA expression levels of ATG5 and ATG7 depending on m6A.

AC008440.5 (AC008)

Target Gene

Osteoarthritis [ICD-11: FA05]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[96]
Responsed Disease	Osteoarthritis [ICD-11: FA05]
Target Regulation	Down regulation
In-vitro Model	Chondrocytes (Chondrocytes were isolated from human cartilage and cultured)
Response Summary	FTO-mediated N6-methyladenosine demethylation downregulated AC008440.5 (AC008) transcription, while lower FTO expression led to upregulation of AC008 transcription in OA.

pri-miR-10a

Target Gene

Brain cancer [ICD-11: 2A00]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[57]
Responsed Disease	Glioblastoma [ICD-11: 2A00.00]
Target Regulation	Up regulation
In-vitro Model	U-87MG ATCC	Glioblastoma	Homo sapiens	CVCL_0022
	U251 (Fibroblasts or fibroblast like cells)
	U-118MG	Astrocytoma	Homo sapiens	CVCL_0633
	LN-229	Glioblastoma	Homo sapiens	CVCL_0393
	A-172	Glioblastoma	Homo sapiens	CVCL_0131
In-vivo Model	BALB/c male nude mice were 4 weeks old. GBM cells with stable overexpression or knockdown of FTO and ovNC or shNC were transduced with lentivirus expressing luciferase. The cells were intracranially injected at a density of 5 × 10⁵/10 uL into every mouse to form an orthotopic xenograft model. Coordinates of injection were 1 mm anterior and 2.5 mm right to the bregma, at a depth of 3.5 mm (the right frontal lobes of the mouse). Every 6 days, bioluminescence imaging (IVIS Lumina Series III; PerkinElmer, Waltham, MA) was used to image the mouse. At 8 days, we randomly chose 5 mice from each group to euthanize them, and their brain tissues were fixed with paraformaldehyde for further study. Another 5 mice were used for survival time analysis. For DB2313 (563801; MedKoo) anti-tumor research, male nude mice were subcutaneously injected with 5 × 10⁶ U87MG cells suspended in 0.1 mL PBS. After 7 days, mice were intraperitoneally injected with DB2313 at density of 10 mg/kg/day dissolved in PBS solvent containing 10% DMSO for 7 days. The other group treated with vehicle only was set as the control group.
Response Summary	FTO inhibited growth, migration and invasion of GBM cells in vitro and in vivo.decreased FTO expression could induce the downregulation of MTMR3 expression by modulating the processing of pri-miR-10a in an m6A/HNRNPA2B1-dependent manner in GBM cells. Furthermore, the transcriptional activity of FTO was inhibited by the transcription factor SPI1.

Unspecific Target Gene

Viral infections [ICD-11: 1D9Y]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[98]
Responsed Disease	Viral infections [ICD-11: 1D9Y]
In-vitro Model	HEK293T	Normal	Homo sapiens	CVCL_0063
Response Summary	m6A is the most abundant internal modification described in eukaryotic mRNA and several viral RNA including human respiratory syncytial virus (HRSV) infection. METTL3/METTL14 m6A writer complex plays a negative role in HRSV infections protein synthesis and viral titers, while m6A erasers FTO and ALKBH5 had the opposite effect.

Solid tumour/cancer [ICD-11: 2A00-2F9Z]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[99]
Responsed Disease	Solid tumour/cancer [ICD-11: 2A00-2F9Z]
Pathway Response	PI3K-Akt signaling pathway	hsa04151
	MAPK signaling pathway	hsa04010
	mTOR signaling pathway	hsa04150
Cell Process	Cell apoptosis
Response Summary	FTO was implicated in multiple biological processes, such as cancer cell apoptosis, proliferation, migration, invasion, metastasis, cell-cycle, differentiation, stem cell self-renewal and so on.

Acute myeloid leukaemia [ICD-11: 2A60]

In total 2 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[102]
Responsed Disease	Acute myeloid leukaemia [ICD-11: 2A60]
Responsed Drug	Saikosaponins		Investigative	Drug Info
Cell Process	Cell apoptosis
Cell Process	Cell-cycle
In-vitro Model	C1498	Mouse leukemia	Mus musculus	CVCL_3494
	HL-60	Adult acute myeloid leukemia	Homo sapiens	CVCL_0002
	K-562	Chronic myelogenous leukemia	Homo sapiens	CVCL_0004
	Kasumi-1	Myeloid leukemia with maturation	Homo sapiens	CVCL_0589
	MOLM-13	Adult acute myeloid leukemia	Homo sapiens	CVCL_2119
	MOLM-14	Adult acute myeloid leukemia	Homo sapiens	CVCL_7916
	MV4-11	Childhood acute monocytic leukemia	Homo sapiens	CVCL_0064
	NB4	Acute promyelocytic leukemia	Homo sapiens	CVCL_0005
	SKNO-1	Myeloid leukemia with maturation	Homo sapiens	CVCL_2196
	U-937	Adult acute monocytic leukemia	Homo sapiens	CVCL_0007
In-vivo Model	Upon the development of leukemic disease (established using a white blood cell (WBC) count), 0.1 mg/kg or 0.5 mg/kg of SsD was intraperitoneally injected three times per week for three consecutive weeks.
Response Summary	FTO-dependent m6A RNA methylation mediated the anti-leukemic actions of saikosaponin-d, thereby opening a window to develop SsD as an epitranscriptome-base drug for leukemia therapy. SsD showed a broadly-suppressed acute myeloid leukemia cell proliferation and promoted apoptosis and cell-cycle arrest both in vitro and in vivo.
Experiment 2 Reporting the m6A-centered Disease Response of This Target Gene				[103]
Responsed Disease	Acute myeloid leukaemia [ICD-11: 2A60]
Response Summary	A prevalent eukaryotic N6-methyladensosine (m6A) post-transcriptional mark can be "erased" by the m6A demethylase FTO, which is commonly deregulated in acute myeloid leukemia (AML).

Malignant haematopoietic neoplasm [ICD-11: 2B33]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[105]
Responsed Disease	Leukaemia [ICD-11: 2B33.4]
In-vitro Model	MV4-11	Childhood acute monocytic leukemia	Homo sapiens	CVCL_0064
	Ku812	Chronic myeloid leukemia	Homo sapiens	CVCL_0379
	Kasumi-1	Myeloid leukemia with maturation	Homo sapiens	CVCL_0589
	K-562	Chronic myelogenous leukemia	Homo sapiens	CVCL_0004
In-vivo Model	All mice had free access to food and water throughout the study. To test the oncogenic potential of FTO gene, K562 parental cells were transfected with FTO expression or control vectors for 6 h, and 5.0 × 10⁶ transfected cells were subcutaneously injected into the bilateral flanks of the nude mice. For therapeutic experiments, K562 nilotinibR cells (1.5 × 10⁶) were injected subcutaneously into the bilateral flanks of the nude mice. To retain the resistance phenotypes, these mice received 1 mg/kg nilotinib twice a week for 4 weeks till the tumor approached ~10 mm³. Then the tumor-bearing mice were randomly divided into groups of 3 animals and received intraperitoneal injection of either 5 mg/kg nilotinib, 10 mg/kg rhein alone or their combination in polyethylene glycol 400 (PEG400, Sigma #1546445) and saline (ratio 15:38:47), three injections each week for 5 times in total.
Response Summary	Developing resistant phenotypes during tyrosine kinase inhibitor (TKI) therapy depends on m6A reduction resulting from FTO overexpression in leukemia cells.

Osteosarcoma [ICD-11: 2B51]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[106]
Responsed Disease	Osteosarcoma [ICD-11: 2B51]
In-vitro Model	MG-63	Osteosarcoma	Homo sapiens	CVCL_0426
In-vivo Model	According to the method published previously , exponentially growing MG63 and MG63/DXR were harvested, counted with trypan blue to show cells with at least 95% viability, and then resuspended at a final amount from 5 × 10⁶ to 5 × 10³ in 100 uL Matrigel (Corning, NY, USA) before being injected subcutaneously into 5-week-old female nude mice.The mice were monitored once every 3 days until the 60th day, and euthanized humanely after the experiment
Response Summary	The transcriptome-wide m6A methylome of osteosarcoma cells enriched by chemotherapy, revealing a tight relationship between m6A methylation and the emergence and maintaining of OSCs.

Gastric cancer [ICD-11: 2B72]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[107]
Responsed Disease	Gastric cancer [ICD-11: 2B72]
Response Summary	Aberrant expression of demethylase genes, FTO and ALKBH1, has a distinct prognostic value in Gastric cancer patients, indicating that FTO and ALKBH1 play vital roles in GC progression and metastasis.

Colorectal cancer [ICD-11: 2B91]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[34]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Cell Process	Cell proliferation
Cell Process	Cell apoptosis
In-vitro Model	HCT 8	Colon adenocarcinoma	Homo sapiens	CVCL_2478
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
	SW620	Colon adenocarcinoma	Homo sapiens	CVCL_0547
In-vivo Model	RC cells SW480 at logarithmic growth phase were prepared into cell suspension with a concentration of about 1 × 10⁷/100 L, which was then injected into the left axilla of nude mice with a 1 ml syringe to establish a subcutaneous mouse xenograft model. Once the tumor volume reached about 50 mm³, the nude mice were injected with miR-96 antagomir or NC antagomir (10 nmol once every 5 days for 5 weeks). After 5 weeks, the mice were euthanized, after which the subcutaneous transplanted tumor was removed, and weighed.
Response Summary	miR-96 antagomir could potentially retard the cancerogenesis in colorectal cancer via AMPK subunit alpha-2 (AMPKAlpha2/PRKAA2)-dependent inhibition of FTO and blocking FTO-mediated m6A modification of MYC.

Liver cancer [ICD-11: 2C12]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[111]
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Cell Process	Cell apoptosis
Cell Process	Cell invasion
In-vitro Model	BEL-7402	Endocervical adenocarcinoma	Homo sapiens	CVCL_5492
	BEL-7404	Endocervical adenocarcinoma	Homo sapiens	CVCL_6568
	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
	MHCC97-L	Adult hepatocellular carcinoma	Homo sapiens	CVCL_4973
	LM	Extrarenal rhabdoid tumor of the liver	Homo sapiens	CVCL_B3QF
	QGY-7703	Endocervical adenocarcinoma	Homo sapiens	CVCL_6715
	SMMC-7721	Endocervical adenocarcinoma	Homo sapiens	CVCL_0534
In-vivo Model	Male BALB/c nude mice (5 weeks old) were subcutaneously inoculated in the right axillary fossa with 200 uL (1 × 10⁶ cells) of SIRT1-overexpressing Hep3B cells, SIRT1- and FTO-overexpressing Hep3B cells, shRNA-SIRT1-transfected HepG2 cells, shRNA-SIRT1- and shRNA-FTO-transfected HepG2 cells, and control cells.
Response Summary	SIRT1 destabilizes FTO, steering the m6A of downstream molecules and subsequent mRNA expression in hepatocellular carcinoma tumorigenesis. A crucial component of small ubiquitin-related modifiers (SUMOs) E3 ligase, RANBP2, is activated by SIRT1, and it is indispensable for FTO SUMOylation at Lysine (K)-216 site that promotes FTO degradation.

Lung cancer [ICD-11: 2C25]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[113]
Responsed Disease	Lung adenocarcinoma [ICD-11: 2C25.0]
Cell Process	Cell Progression
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
In-vitro Model	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
Response Summary	FTO facilitates lung adenocarcinoma cell progression by activating cell migration through m6A demethylation.

Ovarian cancer [ICD-11: 2C73]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[114]
Responsed Disease	Ovarian cancer [ICD-11: 2C73]
Target Regulation	Up regulation
Pathway Response	cAMP signaling pathway			hsa04024
In-vitro Model	COV362	Ovarian serous adenocarcinoma	Homo sapiens	CVCL_2420
	HEK293T	Normal	Homo sapiens	CVCL_0063
	OVCAR-5	Ovarian serous adenocarcinoma	Homo sapiens	CVCL_1628
	SK-OV-3	Ovarian serous cystadenocarcinoma	Homo sapiens	CVCL_0532
In-vivo Model	Female nude, athymic, BALB/c-nu/nu mice (6-7 weeks old; Harlan) were injected subcutaneously (s.c.) with serially diluted numbers (5,000, 10,000, or 20,000) of OVCAR5_GFP or OVCAR5_FTO cells mixed with Matrigel (Fisher Scientific). Mice were monitored bi-weekly and time to tumor initiation and tumor growth were recorded.
Response Summary	FTO-Dependent N 6-Methyladenosine Modifications Inhibit Ovarian Cancer Stem Cell Self-Renewal by Blocking cAMP Signaling. cAMP pathway as a new FTO target in CSCs, associated with tumor inhibiting functions, and provide key new information on the role of m6A modifications regulated by FTO in the fine tuning of cellular fate in HGSOC.

Prostate cancer [ICD-11: 2C82]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[115]
Responsed Disease	Prostate cancer [ICD-11: 2C82]
Cell Process	Cell migration
	Cell invasion
In-vitro Model	PC-3	Prostate carcinoma	Homo sapiens	CVCL_0035
	DU145	Prostate carcinoma	Homo sapiens	CVCL_0105
Response Summary	Knockdown of HNRNPA2B1 or FTO prominently inhibited prostate cancer cells migration and invasion in vitro experiment. Determined CBLL1, FTO, YTHDC1, HNRNPA2B1 as crucial m6A regulators of prostate cancer.

Renal cell carcinoma [ICD-11: 2C90]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[117]
Responsed Disease	Renal cell carcinoma of kidney [ICD-11: 2C90.0]
Response Summary	The m6A-demethylases ALKBH5 and FTO are dysregulated in clear cell renal cell carcinoma and could be used as prognostic biomarkers. ALKBH5 mRNA, as well as ALKBH5 and FTO protein expressions, was significantly downregulated in ccRCC compared to normal tissue and most of the other studied tumour entities.

Diabetes [ICD-11: 5A10-5A14]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[120]
Responsed Disease	Diabetes [ICD-11: 5A10-5A14]
Response Summary	The content of m6A was highly associated with the risk of T2DM, and the increased mRNA expression of FTO is responsible for the reduction of m6A, which can further cause the complications of T2DM.

Obesity [ICD-11: 5B81]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[121]
Responsed Disease	Obesity [ICD-11: 5B81]
In-vitro Model	N1E-115	Mouse neuroblastoma	Mus musculus	CVCL_0451
In-vitro Model	NIH 3T3	Normal	Mus musculus	CVCL_0594
In-vivo Model	For high-fat-diet treatment, 3-week-old male mice were randomly divided into three groups: two experimental groups freely fed with HFD of 60% fat, 20% carbohydrate, and 20% protein (Cat#: D12492, Research Diets) or KD of 89.5% fat, 0.1% carbohydrate, and 10.4% protein (Cat#: D12369B, Research Diets), and the control group fed with SD of 10% fat, 70% carbohydrate, and 20% protein (Cat#: D12450B, Research Diets), respectively. The mice were allowed free access to water and food.For fasting treatment, 3-month-old male mice were randomly divided into two groups: the fasting group with only free access to water for 48 h and the control group allowed free access to water and SD.
Response Summary	FTO fails to bind to its own promoter that promotes FTO expression in the hypothalamus of high-fat diet-induced obese and 48-h fasting mice, suggesting a disruption of the stable expression of this gene.ketogenic diet-derived ketone body beta-hydroxybutyrate (BHB) transiently increases FTO expression in both mouse hypothalamus and cultured cells.

Metabolic disorders [ICD-11: 5D2Z]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[122]
Responsed Disease	Metabolic disorders [ICD-11: 5D2Z]
Pathway Response	AMPK signaling pathway			hsa04152
Cell Process	Lipid metabolism
In-vitro Model	C2C12	Normal	Mus musculus	CVCL_0188
In-vivo Model	Sixteen 10-wk-old male C57BL/6 J mice [wild-type (WT) mice] and six 10-wk-old male obese C57BL/6J^ob/ob (OB) mice were purchased from Nanjing Biomedical Research Institute of Nanjing University. WT mice were randomly divided into 2 groups (8 mice/group): normal chow diet (ND) and high-fat diet (HFD) groups. The ND group was fed with a normal chow diet containing10% fat, 20% protein and 70% carbohydrate. The HFD group was fed a HFD containing 45% fat, 20% protein and 35% carbohydrate. OB mice were fed with ND. All mice were housed at 22 ± 1 ℃ under a 12-h light cycle with free access to water and diet during the experiment.
Response Summary	FTO-dependent demethylation of mRNA m6A methylation was involved in the regulation of skeletal muscle lipid accumulation by the AMPK signalling pathway.

Secondary stereotypy [ICD-11: 8A07]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[123]
Responsed Disease	Secondary stereotypy [ICD-11: 8A07]
Response Summary	Inhibition of m6A RNA demethylation by small-molecule drugs, as presented here, has therapeutic potential and provides tools for the identification of disease-modifying m6A RNAs in neurogenesis and neuroregeneration. Small-molecule inhibitors of the RNA m6A demethylases FTO potently support the survival of dopamine neurons.

Alzheimer disease [ICD-11: 8A20]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[124]
Responsed Disease	Alzheimer disease [ICD-11: 8A20]
Cell Process	Synaptic or neuron development and growth
Response Summary	The alterations of m6A RNA methylation in alzheimer's disease and in C57BL/6 mice were investigated using high-throughput sequencing. The expression of the m6A methyltransferase METTL3 was elevated and that of the m6A demethylase FTO was decreased in AD mice.

Neurological disorders due to toxicity [ICD-11: 8D43]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[126]
Responsed Disease	Neurological disorders due to toxicity [ICD-11: 8D43]
Responsed Drug	Arsenite		Phase 2	Drug Info
In-vitro Model	PC-12 Adh	Rat adrenal gland pheochromocytoma	Rattus norvegicus	CVCL_F659
In-vivo Model	The animals were kept in standard laboratory polycarbonate cages in controlled ambient temperature at 23℃ ± 1℃ with relative humidity of 50% ± 10%, and a light-dark cycle of 12/12 h. The mice had free access to standardized pellet food and tap water. After 1-week of habituation, the animals were randomly divided into the following 4 groups: control group, 0.5 mg/l arsenite group, 5 mg/l arsenite group and 50 mg/l arsenite group (n = 16 per group). The mice were exposed to arsenite via drinking water for 6 months.
Response Summary	targeting the m6A demethylase FTO in the prevention or intervention against arsenite-related neurodegenerative diseases.

Ototoxic hearing loss [ICD-11: AB53]

In total 2 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[127]
Responsed Disease	Ototoxic hearing loss [ICD-11: AB53]
Responsed Drug	Cisplatin		Approved	Drug Info
Cell Process	Oxidative stress
	Cell autophagy
In-vitro Model	HEI-OC1	Normal	Mus musculus	CVCL_D899
Response Summary	MA2, which is a highly selective inhibitor of FTO, has a protective effect and improves the viability of HEI-OC1 cells after cisplatin treatment, and they provide new insights into potential therapeutic targets for the amelioration of cisplatin-induced ototoxicity.
Experiment 2 Reporting the m6A-centered Disease Response of This Target Gene				[127]
Responsed Disease	Ototoxic hearing loss [ICD-11: AB53]
Cell Process	Oxidative stress
	Cell autophagy
In-vitro Model	HEI-OC1	Normal	Mus musculus	CVCL_D899
Response Summary	MA2, which is a highly selective inhibitor of FTO, has a protective effect and improves the viability of HEI-OC1 cells after cisplatin treatment, and they provide new insights into potential therapeutic targets for the amelioration of cisplatin-induced ototoxicity.

Cardiomyopathy [ICD-11: BC43]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[128]
Responsed Disease	Diabetic cardiomyopathy [ICD-11: BC43.7]
In-vivo Model	Leptin receptor-deficient (db/db) mice and control mice (db/ +) were purchased from Shanghai Model Organisms Center, which genetic background is C57BL/6J. All mice were used for experiments at 8-12 weeks old and were housed in constant 24 degrees cages with a 12 h alternating light/dark cycle and free access to water and food. To construct a diabetic heart disease model (DCM), mice were continuously fed to 24 weeks of age, then euthanized, hearts collected in 1.5 ml RNase-free centrifuge tubes, immediately immersed in liquid nitrogen to prevent RNA degradation, and finally stored at 80℃. Five pairs of db/db and db/ + heart samples were selected for RNA sequencing, and the remaining samples were saved for validation.
Response Summary	Overexpression of FTO in diabetic cardiomyopathy(DCM) model mice improved cardiac function by reducing myocardial fibrosis and myocyte hypertrophy.

Congestive heart failure [ICD-11: BD10]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[129]
Responsed Disease	Congestive heart failure [ICD-11: BD10]
In-vivo Model	We quantified m6A levels in RNA extracted from failing human (both ischemic and non-ischemic), pig and mouse (post-myocardial infarction ischemic) hearts and compared them to m6A in non-failing human and sham surgical controls respectively. We detected significantly elevated levels of m6A in both total and polyA+ RNA extracted from human, pig and mouse failing left ventricular (LV) explants compared to non-failing or sham.
Response Summary	FTO-dependent cardiac m6A methylome in cardiac contraction during heart failure and provides a novel mechanistic insight into the therapeutic mechanisms of FTO.

Aortic aneurysm or dissection [ICD-11: BD50]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[130]
Responsed Disease	Abdominal aortic aneurysm [ICD-11: BD50.4]
Cell Process	Inflammatory infiltrates
	Neovascularization
In-vitro Model	PBMCs (Human peripheral blood mononuclear cells (PBMCs) are isolated from peripheral blood and identified as any blood cell with a round nucleus)
	SMCs (Aneurysmal smooth muscle cells)
Response Summary	YTHDF3 represented an even greater risk of rupture. Regarding the cellular location, METTL14 seemed to be associated with inflammatory infiltrates and neovascularization. Furthermore, a strong correlation was seen between FTO and aneurysmal smooth muscle cells (SMCs), YTHDF3, and macrophage infiltrate. The results also reveal the important roles of m6A modulators, including YTHDF3, FTO, and METTL14, in the pathogenesis of human human abdominal aortic aneurysm(AAA) and provide a new view on m6A modification in AAA.

Diseases of the circulatory system [ICD-11: BE2Z]

In total 1 item(s) under this disease			Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene			[131]
Responsed Disease	Diseases of the circulatory system [ICD-11: BE2Z]
Responsed Drug	Sunitinib	Approved	Drug Info
In-vitro Model	hiPSCs (Urinary epithelial cell-derived hiPSCs)
	CMECs (Cardiac Microvascular Endothelial Cells )
	CFs (Cardiac Fibroblasts)
Response Summary	The RNA demethylase FTO was downregulated, whereas METTL14 and WTAP were upregulated. Furthermore, gain- and loss-of-function studies substantiated that FTO is cardioprotective in TKI(Sunitinib).

Non-alcoholic fatty liver disease [ICD-11: DB92]

In total 1 item(s) under this disease			Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene			[132]
Responsed Disease	Non-alcoholic fatty liver disease [ICD-11: DB92]
Responsed Drug	Betaine	Approved	Drug Info
In-vivo Model	Eight adult female C57BL/6 mice from the same pool of litters were housed at 22 ± 1 ℃ with 12-h light cycle and were mated with their male siblings. The female mice were fed with a low-fat diet supplemented with betaine from mating and throughout gestation and lactation. Litters were culled to five males per dam. Thirty offspring weaned at the age of day 21 and then were randomly assigned to three groups fed with either a low-fat diet (LF), high-fat diet (HF), or high-fat diet supplemented with betaine (HB) for 6 weeks.
Response Summary	A novel FTO-dependent function of m(6)A is involve in the hepatoprotective effects of betaine. betaine supplementation across adolescence could protect mice from high-fat-induced lipid accumulation NAFLD in the liver. Moreover, FTO-dependent m6A demethylation is affected by betaine. A novel FTO-dependent function of m(6)A may involve in the hepatoprotective effects of betaine.

Liver disease [ICD-11: DB9Z]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[133]
Responsed Disease	Liver disease [ICD-11: DB9Z]
Pathway Response	PPAR signaling pathway	hsa03320
Cell Process	Fatty degeneration
In-vivo Model	A total of 24 male mice were randomly allocated to LFD (low-fat diet), LFDR (low-fat diet + resveratrol), HFD (high-fat diet), and HFDR (high-fat diet + resveratrol) groups for 12 weeks (n = 6/group).
Response Summary	The beneficial effect of resveratrol on lipid metabolism disorder under HFD is due to a decrease of m6A RNA methylation and an increase of PPARalpha mRNA, providing mechanistic insights into the function of resveratrol in alleviating the disturbance of lipid metabolism in mice. The resveratrol in HFD increased the transcript levels of methyltransferase like 3 (METTL3), alkB homolog 5 (ALKBH5), fat mass and obesity associated protein (FTO), and YTH domain family 2 (YTHDF2), whereas it decreased the level of YTH domain family 3 (YTHDF3) and m6A abundance in mice liver.

Menopausal disorder [ICD-11: GA30]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[134]
Responsed Disease	Premature ovarian failure [ICD-11: GA30.6]
Cell Process	Cell proliferation
	Cell apoptosis
In-vitro Model	Hgc (Primary human ovarian granulosa cells)
In-vivo Model	To build the mouse model for POI, cyclophosphamide (CTX) (Sigma, St. Louis, MO) was used a high-dose treatment (120 mg/kg, 2 weeks).
Response Summary	The decreased mRNA and protein expression levels of FTO are responsible for the increase in m6A in POI, which can further increase the risk of complications of POI. FACS was used to measure the levels of proliferation and apoptosis, and siRNA was used to establish FTO and ALKBH5 knockdown cell lines. The m6A content in the RNA from POI patients and POI mice was significantly higher than control groups and that POI was characterized by the content of m6A.

Chronic kidney disease [ICD-11: GB61]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[136]
Responsed Disease	Chronic kidney disease [ICD-11: GB61]
In-vitro Model	THP-1	Childhood acute monocytic leukemia	Homo sapiens	CVCL_0006
	T-lymphocyte cell line (A type of lymphocyte)
Response Summary	Targeting RNA m6A modification is a novel strategy for the treatment of chronic kidney diseases and autophagy. Knockdown of FTO or inhibit the m6A by 3-deazaadenosine blocks the effects of indoxyl sulfate on autophagy activation in cells.

Sex development malformative disorder [ICD-11: LD2A]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[137]
Responsed Disease	Sex development malformative disorder [ICD-11: LD2A]
Pathway Response	MAPK signaling pathway			hsa04010
Cell Process	Cell apoptosis
In-vitro Model	TM3	Normal	Mus musculus	CVCL_4326
Response Summary	The inhibition of FTO-mediated up-regulation of m6A could be involved in MEHP-induced Leydig cell apoptosis.

Ankyrin repeat and SOCS box protein 2 (ASB2)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by FTO*
Cell Line	NB4 cell line	Homo sapiens
Treatment: shFTO NB4 cells Control: shNS NB4 cells		GSE103494
Regulation		logFC: 8.19E-01 p-value: 3.80E-03
More Results	Click to View More RNA-seq Results

Tretinoin [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[2]
Responsed Disease	Acute myeloid leukaemia		ICD-11: 2A60	Disease Info
Target Regulation	Down regulation
Cell Process	RNA stability
Cell Process	RNA degradation (hsa03018)
In-vitro Model	K-562	Chronic myelogenous leukemia	Homo sapiens	CVCL_0004
	KOCL-48	Childhood acute monocytic leukemia	Homo sapiens	CVCL_6867
	Mono-Mac-6	Adult acute monocytic leukemia	Homo sapiens	CVCL_1426
Response Summary	FTO enhances leukemic oncogene-mediated cell transformation and leukemogenesis, and inhibits all-trans-retinoic acid (ATRA)-induced AML cell differentiation, through regulating expression of targets such as Ankyrin repeat and SOCS box protein 2 (ASB2) and RARA by reducing m6A levels in these mRNA transcripts.

ATP-binding cassette sub-family C member 10 (ABCC10)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by FTO*
Cell Line	Mouse hippocampus	Mus musculus
Treatment: FTO knockout mice hippocampus Control: Wild type hippocampus		GSE94098
Regulation		logFC: 6.58E-01 p-value: 2.09E-04
More Results	Click to View More RNA-seq Results

Gefitinib [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[5]
Responsed Disease	Non-small-cell lung carcinoma		ICD-11: 2C25.Y	Disease Info
Target Regulation	Up regulation
Pathway Response	ABC transporters			hsa02010
In-vitro Model	PC-9	Lung adenocarcinoma	Homo sapiens	CVCL_B260
In-vitro Model	NCI-H1975	Lung adenocarcinoma	Homo sapiens	CVCL_1511
In-vivo Model	Mice were randomized into three groups (n = 7/group), 1 × 10⁷ PC9 cells absorbed exosomes were subcutaneously injected into the Bilateral groin of mice. Treatment began 1 week following injection, the mice were intraperitoneally injected with gefitinib (30 mg/kg/day).
Response Summary	Not only FTO knockdown enhanced the gefitinib sensitivity of GR cells but also FTO reduction in donor exosomes alleviated the acquired resistance of recipient non-small cell lung cancer PC9 cells. FTO/YTHDF2/ATP-binding cassette sub-family C member 10 (ABCC10) axis played a role in intercellular transmission of GR cell-derived exosome-mediated gefitinib resistance.

C-X-C chemokine receptor type 4 (CXCR4)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by FTO*
Cell Line	NB4 cell line	Homo sapiens
Treatment: shFTO NB4 cells Control: shNS NB4 cells		GSE103494
Regulation		logFC: 9.72E-01 p-value: 3.86E-03
More Results	Click to View More RNA-seq Results

PMID31239444-anti-PD1 antibody [Investigative]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[7]
Responsed Disease	Melanoma		ICD-11: 2C30	Disease Info
Target Regulation	Up regulation
Pathway Response	PD-L1 expression and PD-1 checkpoint pathway in cancer			hsa05235
Cell Process	mRNA decay
In-vitro Model	B16-F10	Mouse melanoma	Mus musculus	CVCL_0159
	CHL-1	Melanoma	Homo sapiens	CVCL_1122
	624-mel	Melanoma	Homo sapiens	CVCL_8054
	NHEM (Normal Human Epidermal Melanocytes)
	SK-MEL-30	Cutaneous melanoma	Homo sapiens	CVCL_0039
	WM115	Melanoma	Homo sapiens	CVCL_0040
	WM35	Melanoma	Homo sapiens	CVCL_0580
	WM3670	Melanoma	Homo sapiens	CVCL_6799
	WM793	Melanoma	Homo sapiens	CVCL_8787
In-vivo Model	When the tumors reached a volume of 80-100 mm³, mice were treated with anti-PD-1 or isotype control antibody (200 ug/mouse) by i.p. injection, every other day for three times. For IFNγ blockade treatment, C57BL/6 mice were treated with anti-IFNγ antibody or isotype control IgG (250 ug/mouse) every other day after tumor cell inoculation.
Response Summary	These findings demonstrate a crucial role of FTO as an m6A demethylase in promoting melanoma tumorigenesis and anti-PD-1 resistance, and suggest that the combination of FTO inhibition with anti-PD-1 blockade reduces the resistance to immunotherapy in melanoma. Knockdown of FTO increases m6A methylation in the critical protumorigenic melanoma cell-intrinsic genes including PD-1 (PDCD1), C-X-C chemokine receptor type 4 (CXCR4), and SOX10, leading to increased RNA decay through the m6A reader YTHDF2.

CCAAT/enhancer-binding protein alpha (CEBPA)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by FTO*
Cell Line	NB4 cell line	Homo sapiens
Treatment: shFTO NB4 cells Control: shNS NB4 cells		GSE103494
Regulation		logFC: 6.07E-01 p-value: 3.92E-03
More Results	Click to View More RNA-seq Results

R-2HG [Investigative]

In total 2 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[9]
Responsed Disease	Glioma		ICD-11: 2A00.0	Disease Info
Target Regulation	Down regulation
Cell Process	Glutamine metabolism
Cell Process	Cell apoptosis
In-vitro Model	8-MG-BA	Glioblastoma	Homo sapiens	CVCL_1052
	A-172	Glioblastoma	Homo sapiens	CVCL_0131
	DK-MG	Glioblastoma	Homo sapiens	CVCL_1173
	GaMG	Glioblastoma	Homo sapiens	CVCL_1226
	HEL	Erythroleukemia	Homo sapiens	CVCL_0001
	Jurkat	T acute lymphoblastic leukemia	Homo sapiens	CVCL_0065
	KOCL-45	B acute lymphoblastic leukemia	Homo sapiens	CVCL_3993
	KOCL-48	Childhood acute monocytic leukemia	Homo sapiens	CVCL_6867
	KOCL-50	B acute lymphoblastic leukemia	Homo sapiens	CVCL_6866
	KOCL-51	B acute lymphoblastic leukemia	Homo sapiens	CVCL_6865
	KOCL-69	B acute lymphoblastic leukemia	Homo sapiens	CVCL_3995
	KOPN-1	B acute lymphoblastic leukemia	Homo sapiens	CVCL_3937
	LN-18	Glioblastoma	Homo sapiens	CVCL_0392
	LN-229	Glioblastoma	Homo sapiens	CVCL_0393
	MA9.3 (MA9.3)
	MA9.6ITD (MLL-AF9 plus FLT3-ITD)
	MA9.6RAS (MLL-AF9 plus NRasG12D)
	MA9.6 (MLL-AF9)
	MA9.6ITD (MLL-AF9 plus FLT3-ITD)
	MA9.6RAS (MLL-AF9 plus NRasG12D)
	ME-1 [Human leukemia]	Adult acute myeloid leukemia	Homo sapiens	CVCL_2110
	ML-2	Adult acute myeloid leukemia	Homo sapiens	CVCL_1418
	MV4-11	Childhood acute monocytic leukemia	Homo sapiens	CVCL_0064
	NB4	Acute promyelocytic leukemia	Homo sapiens	CVCL_0005
	NOMO-1	Adult acute monocytic leukemia	Homo sapiens	CVCL_1609
	PL21	Familial adenomatous polyposis	Homo sapiens	CVCL_JM48
	T98G	Glioblastoma	Homo sapiens	CVCL_0556
	THP-1	Childhood acute monocytic leukemia	Homo sapiens	CVCL_0006
	U-87MG ATCC	Glioblastoma	Homo sapiens	CVCL_0022
	U-937	Adult acute monocytic leukemia	Homo sapiens	CVCL_0007
In-vivo Model	For R-2HG injection mouse models, sensitive (NOMO-1 and MA9.3ITD) or resistant (MA9.3RAS) cells were injected into NSGS or NRGS intravenously, and then R-2HG (6mg/kg body weight) or PBS were injected once daily through tail vein for 12 consecutive days starting from day 11 post xeno-transplantation.
Response Summary	This work demonstrates anti-tumor effects of 2HG in inhibiting proliferation/survival of FTO-high cancer cells via targeting FTO/m6A/MYC/CCAAT/enhancer-binding protein alpha (CEBPA) signaling.High levels of FTO sensitize leukemia cells to R-2HG, whereas hyperactivation of MYC signaling confers resistance that can be reversed by the inhibition of MYC signaling. R-2HG also displays anti-tumor activity in glioma. High levels of FTO sensitize leukemic cells to R-2HG, whereas hyperactivation of MYC signaling confers resistance that can be reversed by the inhibition of MYC signaling.
Experiment 2 Reporting the m6A-centered Drug Response of This Target Gene				[9]
Responsed Disease	Leukaemia		ICD-11: 2B33.4	Disease Info
Target Regulation	Down regulation
Cell Process	Glutamine metabolism
Cell Process	Cell apoptosis
In-vitro Model	8-MG-BA	Glioblastoma	Homo sapiens	CVCL_1052
	A-172	Glioblastoma	Homo sapiens	CVCL_0131
	DK-MG	Glioblastoma	Homo sapiens	CVCL_1173
	GaMG	Glioblastoma	Homo sapiens	CVCL_1226
	HEL	Erythroleukemia	Homo sapiens	CVCL_0001
	Jurkat	T acute lymphoblastic leukemia	Homo sapiens	CVCL_0065
	KOCL-45	B acute lymphoblastic leukemia	Homo sapiens	CVCL_3993
	KOCL-48	Childhood acute monocytic leukemia	Homo sapiens	CVCL_6867
	KOCL-50	B acute lymphoblastic leukemia	Homo sapiens	CVCL_6866
	KOCL-51	B acute lymphoblastic leukemia	Homo sapiens	CVCL_6865
	KOCL-69	B acute lymphoblastic leukemia	Homo sapiens	CVCL_3995
	KOPN-1	B acute lymphoblastic leukemia	Homo sapiens	CVCL_3937
	LN-18	Glioblastoma	Homo sapiens	CVCL_0392
	LN-229	Glioblastoma	Homo sapiens	CVCL_0393
	MA9.3 (MA9.3)
	MA9.6ITD (MLL-AF9 plus FLT3-ITD)
	MA9.6RAS (MLL-AF9 plus NRasG12D)
	MA9.6 (MLL-AF9)
	MA9.6ITD (MLL-AF9 plus FLT3-ITD)
	MA9.6RAS (MLL-AF9 plus NRasG12D)
	ME-1 [Human leukemia]	Adult acute myeloid leukemia	Homo sapiens	CVCL_2110
	ML-2	Adult acute myeloid leukemia	Homo sapiens	CVCL_1418
	MV4-11	Childhood acute monocytic leukemia	Homo sapiens	CVCL_0064
	NB4	Acute promyelocytic leukemia	Homo sapiens	CVCL_0005
	NOMO-1	Adult acute monocytic leukemia	Homo sapiens	CVCL_1609
	PL21	Familial adenomatous polyposis	Homo sapiens	CVCL_JM48
	T98G	Glioblastoma	Homo sapiens	CVCL_0556
	THP-1	Childhood acute monocytic leukemia	Homo sapiens	CVCL_0006
	U-87MG ATCC	Glioblastoma	Homo sapiens	CVCL_0022
	U-937	Adult acute monocytic leukemia	Homo sapiens	CVCL_0007
In-vivo Model	For R-2HG injection mouse models, sensitive (NOMO-1 and MA9.3ITD) or resistant (MA9.3RAS) cells were injected into NSGS or NRGS intravenously, and then R-2HG (6mg/kg body weight) or PBS were injected once daily through tail vein for 12 consecutive days starting from day 11 post xeno-transplantation.
Response Summary	This work demonstrates anti-tumor effects of 2HG in inhibiting proliferation/survival of FTO-high cancer cells via targeting FTO/m6A/MYC/CCAAT/enhancer-binding protein alpha (CEBPA) signaling.High levels of FTO sensitize leukemia cells to R-2HG, whereas hyperactivation of MYC signaling confers resistance that can be reversed by the inhibition of MYC signaling. R-2HG also displays anti-tumor activity in glioma. High levels of FTO sensitize leukemic cells to R-2HG, whereas hyperactivation of MYC signaling confers resistance that can be reversed by the inhibition of MYC signaling.

Cyclic AMP-dependent transcription factor ATF-4 (ATF4)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by FTO*
Cell Line	253J cell line	Homo sapiens
Treatment: siFTO 253J cells Control: 253J cells		GSE150239
Regulation		logFC: -1.42E+00 p-value: 2.68E-47
More Results	Click to View More RNA-seq Results

Asparagine inhibitor [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[12]
Responsed Disease	Colorectal cancer		ICD-11: 2B91	Disease Info
Pathway Response	mTOR signaling pathway			hsa04150
Cell Process	RNA decay
	Cell growth and death
	Cell autophagy
In-vitro Model	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
Response Summary	In colorectal cancer, Glutaminolysis inhibition upregulated ATF4 expression in an m6A-dependent manner to activate pro-survival autophagy through transcriptional activation of the mTOR inhibitor DDIT4. Determined the relationship between FTO alpha-ketoglutarate dependent dioxygenase (FTO), YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), and ATF4. ATF4 transcriptionally upregulated DDIT4 to suppress Cyclic AMP-dependent transcription factor ATF-4 (ATF4), which induced pro-survival autophagy during glutaminolysis inhibition.

Chloroquine [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[12]
Responsed Disease	Colorectal cancer		ICD-11: 2B91	Disease Info
Pathway Response	mTOR signaling pathway			hsa04150
Cell Process	RNA decay
	Cell growth and death
	Cell autophagy
In-vitro Model	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
Response Summary	In colorectal cancer, Glutaminolysis inhibition upregulated ATF4 expression in an m6A-dependent manner to activate pro-survival autophagy through transcriptional activation of the mTOR inhibitor DDIT4. Determined the relationship between FTO alpha-ketoglutarate dependent dioxygenase (FTO), YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), and ATF4. ATF4 transcriptionally upregulated DDIT4 to suppress Cyclic AMP-dependent transcription factor ATF-4 (ATF4), which induced pro-survival autophagy during glutaminolysis inhibition.

Meclofenamate sodium [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[12]
Responsed Disease	Colorectal cancer		ICD-11: 2B91	Disease Info
Pathway Response	mTOR signaling pathway			hsa04150
Cell Process	RNA decay
	Cell growth and death
	Cell autophagy
In-vitro Model	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
Response Summary	In colorectal cancer, Glutaminolysis inhibition upregulated ATF4 expression in an m6A-dependent manner to activate pro-survival autophagy through transcriptional activation of the mTOR inhibitor DDIT4. Determined the relationship between FTO alpha-ketoglutarate dependent dioxygenase (FTO), YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), and ATF4. Cyclic AMP-dependent transcription factor ATF-4 (ATF4) transcriptionally upregulated DDIT4 to suppress mTOR, which induced pro-survival autophagy during glutaminolysis inhibition.

Rapamycin [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[12]
Responsed Disease	Colorectal cancer		ICD-11: 2B91	Disease Info
Pathway Response	mTOR signaling pathway			hsa04150
Cell Process	RNA decay
	Cell growth and death
	Cell autophagy
In-vitro Model	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
Response Summary	In colorectal cancer, Glutaminolysis inhibition upregulated ATF4 expression in an m6A-dependent manner to activate pro-survival autophagy through transcriptional activation of the mTOR inhibitor DDIT4. Determined the relationship between FTO alpha-ketoglutarate dependent dioxygenase (FTO), YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), and ATF4. Cyclic AMP-dependent transcription factor ATF-4 (ATF4) transcriptionally upregulated DDIT4 to suppress mTOR, which induced pro-survival autophagy during glutaminolysis inhibition.

CB-839 [Phase 2]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[12]
Responsed Disease	Colorectal cancer		ICD-11: 2B91	Disease Info
Pathway Response	mTOR signaling pathway			hsa04150
Cell Process	RNA decay
	Cell growth and death
	Cell autophagy
In-vitro Model	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
Response Summary	In colorectal cancer, Glutaminolysis inhibition upregulated ATF4 expression in an m6A-dependent manner to activate pro-survival autophagy through transcriptional activation of the mTOR inhibitor DDIT4. Determined the relationship between FTO alpha-ketoglutarate dependent dioxygenase (FTO), YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), and ATF4. Cyclic AMP-dependent transcription factor ATF-4 (ATF4) transcriptionally upregulated DDIT4 to suppress mTOR, which induced pro-survival autophagy during glutaminolysis inhibition.

GLS-IN-968 [Investigative]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[12]
Responsed Disease	Colorectal cancer		ICD-11: 2B91	Disease Info
Pathway Response	mTOR signaling pathway			hsa04150
Cell Process	RNA decay
	Cell growth and death
	Cell autophagy
In-vitro Model	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
Response Summary	In colorectal cancer, Glutaminolysis inhibition upregulated ATF4 expression in an m6A-dependent manner to activate pro-survival autophagy through transcriptional activation of the mTOR inhibitor DDIT4. Determined the relationship between FTO alpha-ketoglutarate dependent dioxygenase (FTO), YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), and ATF4. ATF4 transcriptionally upregulated DDIT4 to suppress Cyclic AMP-dependent transcription factor ATF-4 (ATF4), which induced pro-survival autophagy during glutaminolysis inhibition.

Cyclin-A2 (CCNA2)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by FTO*
Cell Line	Cerebral cortex	Mus musculus
Treatment: METTL3 (f/f, Emx1-cre) cerebral cortex Control: Wild type cerebral cortex		GSE154992
Regulation		logFC: 7.89E-01 p-value: 6.22E-11
More Results	Click to View More RNA-seq Results

Epigallocatechin gallate [Phase 3]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[13]
Responsed Disease	Obesity		ICD-11: 5B81	Disease Info
Target Regulation	Up regulation
Pathway Response	Cell cycle			hsa04110
Cell Process	Adipogenesis
In-vitro Model	3T3-L1	Normal	Mus musculus	CVCL_0123
Response Summary	m6A-dependent Cyclin-A2 (CCNA2) and CDK2 expressions mediated by FTO and YTHDF2 contributed to EGCG-induced adipogenesis inhibition.

Cyclin-dependent kinase 2 (CDK2)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by FTO*
Cell Line	B16-OVA cell line	Mus musculus
Treatment: shFTO B16-OVA cells Control: shNC B16-OVA cells		GSE154952
Regulation		logFC: 7.39E-01 p-value: 1.49E-28
More Results	Click to View More RNA-seq Results

Epigallocatechin gallate [Phase 3]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[13]
Responsed Disease	Obesity		ICD-11: 5B81	Disease Info
Target Regulation	Up regulation
Pathway Response	Cell cycle			hsa04110
Cell Process	Adipogenesis
In-vitro Model	3T3-L1	Normal	Mus musculus	CVCL_0123
Response Summary	m6A-dependent CCNA2 and Cyclin-dependent kinase 2 (CDK2) expressions mediated by FTO and YTHDF2 contributed to EGCG-induced adipogenesis inhibition.

DNA damage-inducible transcript 3 protein (DDIT3/CHOP)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by FTO*
Cell Line	NB4 cell line	Homo sapiens
Treatment: shFTO NB4 cells Control: shNS NB4 cells		GSE103494
Regulation		logFC: 7.94E-01 p-value: 7.54E-04
More Results	Click to View More RNA-seq Results

Cisplatin [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[19]
Responsed Disease	Gastric cancer		ICD-11: 2B72	Disease Info
Target Regulation	Down regulation
Pathway Response	mTOR signaling pathway			hsa04150
	Apoptosis			hsa04210
Cell Process	Cell apoptosis
In-vitro Model	AGS	Gastric adenocarcinoma	Homo sapiens	CVCL_0139
	HGC-27	Gastric carcinoma	Homo sapiens	CVCL_1279
Response Summary	Omeprazole pretreatment could enhance the inhibitory effect of 5-Fu, DDP and TAX on gastric cancer cells. FTO inhibition induced by omeprazole enhanced the activation of mTORC1 signal pathway that inhibited the prosurvival autophagy so as to improve the antitumor efficiency of chemotherapeutic drugs on GC cells. Meanwhile, transcript level of DNA damage-inducible transcript 3 protein (DDIT3), which is an apoptosis-related tumor suppressor gene downstream of mTORC1, was regulated by omeprazole-induced FTO silence through an m6A-dependent mechanism. m6A modification and its eraser FTO plays a role in the improvement of chemosensitivity mediated by proton pump inhibitor omeprazole.

Fluorouracil [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[19]
Responsed Disease	Gastric cancer		ICD-11: 2B72	Disease Info
Target Regulation	Down regulation
Pathway Response	mTOR signaling pathway			hsa04150
	Apoptosis			hsa04210
Cell Process	Cell apoptosis
In-vitro Model	AGS	Gastric adenocarcinoma	Homo sapiens	CVCL_0139
	HGC-27	Gastric carcinoma	Homo sapiens	CVCL_1279
Response Summary	Omeprazole pretreatment could enhance the inhibitory effect of 5-Fu, DDP and TAX on gastric cancer cells. FTO inhibition induced by omeprazole enhanced the activation of mTORC1 signal pathway that inhibited the prosurvival autophagy so as to improve the antitumor efficiency of chemotherapeutic drugs on GC cells. Meanwhile, transcript level of DNA damage-inducible transcript 3 protein (DDIT3), which is an apoptosis-related tumor suppressor gene downstream of mTORC1, was regulated by omeprazole-induced FTO silence through an m6A-dependent mechanism. m6A modification and its eraser FTO plays a role in the improvement of chemosensitivity mediated by proton pump inhibitor omeprazole.

Paclitaxel [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[19]
Responsed Disease	Gastric cancer		ICD-11: 2B72	Disease Info
Target Regulation	Down regulation
Pathway Response	mTOR signaling pathway			hsa04150
	Apoptosis			hsa04210
Cell Process	Cell apoptosis
In-vitro Model	AGS	Gastric adenocarcinoma	Homo sapiens	CVCL_0139
	HGC-27	Gastric carcinoma	Homo sapiens	CVCL_1279
Response Summary	Omeprazole pretreatment could enhance the inhibitory effect of 5-Fu, DDP and TAX on gastric cancer cells. FTO inhibition induced by omeprazole enhanced the activation of mTORC1 signal pathway that inhibited the prosurvival autophagy so as to improve the antitumor efficiency of chemotherapeutic drugs on GC cells. Meanwhile, transcript level of DNA damage-inducible transcript 3 protein (DDIT3), which is an apoptosis-related tumor suppressor gene downstream of mTORC1, was regulated by omeprazole-induced FTO silence through an m6A-dependent mechanism. m6A modification and its eraser FTO plays a role in the improvement of chemosensitivity mediated by proton pump inhibitor omeprazole.

Frizzled-10 (FZD10)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by FTO*
Cell Line	Mouse hippocampus	Mus musculus
Treatment: FTO knockout mice hippocampus Control: Wild type hippocampus		GSE94098
Regulation		logFC: -6.03E-01 p-value: 7.74E-04
More Results	Click to View More RNA-seq Results

PARPi [Investigative]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[21]
Responsed Disease	Malignant mixed epithelial mesenchymal tumour of ovary		ICD-11: 2B5D.0	Disease Info
Target Regulation	Down regulation
Pathway Response	Wnt signaling pathway			hsa04310
In-vitro Model	UWB1.289	Ovarian carcinoma	Homo sapiens	CVCL_B079
In-vitro Model	PEO1	Ovarian cystadenocarcinoma	Homo sapiens	CVCL_2686
In-vivo Model	2 × 10⁷ PARP inhibitor resistant PEO1 cells were suspended in 200 uL PBS : Matrigel (1:1) unilaterally injected subcutaneously into the right dorsal flank of 6-8 week-old female immunocompromised non-obese diabetic/severe combined immunodeficiency (NOD/SCID) gamma (NSG) mice. When the average tumor size reached ~100 mm3, the mice were then randomized into four groups and treated with vehicle control, Olaparib (50 mg/kg), XAV939 (5 mg/kg) or a combination daily for 18 days.
Response Summary	Downregulation of m6A demethylases FTO and ALKBH5 was sufficient to increase Frizzled-10 (FZD10) mRNA m6A modification and reduce PARPi sensitivity, the finding elucidates a novel regulatory mechanism of PARPi resistance in EOC by showing that m6A modification of FZD10 mRNA contributes to PARPi resistance in BRCA-deficient EOC cells via upregulation of Wnt/Bete-catenin pathway.

Heat shock factor protein 1 (HSF1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by FTO*
Cell Line	NB4 cell line	Homo sapiens
Treatment: shFTO NB4 cells Control: shNS NB4 cells		GSE103494
Regulation		logFC: -7.09E-01 p-value: 1.48E-02
More Results	Click to View More RNA-seq Results

Bortezomib [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[25]
Responsed Disease	Multiple myeloma		ICD-11: 2A83.1	Disease Info
Target Regulation	Up regulation
In-vitro Model	RPMI-8226	Plasma cell myeloma	Homo sapiens	CVCL_0014
In-vitro Model	MM1.R	Plasma cell myeloma	Homo sapiens	CVCL_8794
In-vivo Model	A total of 3×10⁶ RPMI8226/MM1R-Luc cells were intravenously injected into NCG mice to establish a disseminated human MM xenograft model. The in vivo antitumor effect of the FTO inhibitor MA2 combined with or without the first-line chemotherapeutic agent BTZ was evaluated as follows: 3 days post xenotransplantation, MA2 (20 mg/kg), or vehicle control was injected intraperitoneally (i.p.) daily for 10 days, and BTZ was injected intraperitoneally on days 1, 4, 8, and 11. Mouse serum was collected at specified time points during the treatment, and the tumor burden was monitored by detecting myeloma cell-secreted Lambda light chains via a Human Lambda ELISA Kit (Bethyl Laboratories, No. E88-116). Tumor development was monitored weekly after treatment with an in vivo imaging system (IVIS, SI Imaging, Lago, and LagoX). Luciferin (150 mg/kg, YEASEN, Shanghai, China) was injected intraperitoneally into the mice.
Response Summary	FTO significantly promotes MM cell proliferation, migration, and invasion by targeting Heat shock factor protein 1 (HSF1)/HSPs in a YTHDF2-dependent manner. FTO inhibition, especially when combined with bortezomib (BTZ) treatment, synergistically inhibited myeloma bone tumor formation and extramedullary spread in NCG mice.

Intercellular adhesion molecule 1 (ICAM1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by FTO*
Cell Line	NB4 cell line	Homo sapiens
Treatment: shFTO NB4 cells Control: shNS NB4 cells		GSE103494
Regulation		logFC: 1.83E+00 p-value: 2.17E-03
More Results	Click to View More RNA-seq Results

Atorvastatin [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[29]
Responsed Disease	Vascular diseases		ICD-11: BE2Z	Disease Info
Target Regulation	Up regulation
In-vitro Model	THP-1	Childhood acute monocytic leukemia	Homo sapiens	CVCL_0006
	HUVEC-C	Normal	Homo sapiens	CVCL_2959
	HEK293T	Normal	Homo sapiens	CVCL_0063
Response Summary	FTO overexpression significantly upregulated the mRNA and protein levels of VCAM-1 and Intercellular adhesion molecule 1 (ICAM1), downregulated those of KLF2 and eNOS, and strongly attenuated the atorvastatin-mediated induction of KLF2 and eNOS expression. FTO could serve as a novel molecular target to modulate endothelial function in vascular diseases.

Krueppel-like factor 2 (KLF2)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by FTO*
Cell Line	B16F10 cell line	Mus musculus
Treatment: FTO knockout B16F10 cells Control: B16F10 cells		GSE134388
Regulation		logFC: -1.68E+00 p-value: 3.25E-02
More Results	Click to View More RNA-seq Results

Atorvastatin [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[29]
Responsed Disease	Vascular diseases		ICD-11: BE2Z	Disease Info
Target Regulation	Down regulation
In-vitro Model	THP-1	Childhood acute monocytic leukemia	Homo sapiens	CVCL_0006
	HUVEC-C	Normal	Homo sapiens	CVCL_2959
	HEK293T	Normal	Homo sapiens	CVCL_0063
Response Summary	FTO overexpression significantly upregulated the mRNA and protein levels of VCAM-1 and ICAM-1, downregulated those of Krueppel-like factor 2 (KLF2) and eNOS, and strongly attenuated the atorvastatin-mediated induction of KLF2 and eNOS expression. FTO could serve as a novel molecular target to modulate endothelial function in vascular diseases.

Myc proto-oncogene protein (MYC)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by FTO*
Cell Line	NB4 cell line	Homo sapiens
Treatment: shFTO NB4 cells Control: shNS NB4 cells		GSE103494
Regulation		logFC: -6.81E-01 p-value: 3.45E-03
More Results	Click to View More RNA-seq Results

R-2HG [Investigative]

In total 2 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[9]
Responsed Disease	Glioma		ICD-11: 2A00.0	Disease Info
Target Regulation	Down regulation
Cell Process	Glutamine metabolism
Cell Process	Cell apoptosis
In-vitro Model	8-MG-BA	Glioblastoma	Homo sapiens	CVCL_1052
	A-172	Glioblastoma	Homo sapiens	CVCL_0131
	DK-MG	Glioblastoma	Homo sapiens	CVCL_1173
	GaMG	Glioblastoma	Homo sapiens	CVCL_1226
	HEL	Erythroleukemia	Homo sapiens	CVCL_0001
	Jurkat	T acute lymphoblastic leukemia	Homo sapiens	CVCL_0065
	KOCL-45	B acute lymphoblastic leukemia	Homo sapiens	CVCL_3993
	KOCL-48	Childhood acute monocytic leukemia	Homo sapiens	CVCL_6867
	KOCL-50	B acute lymphoblastic leukemia	Homo sapiens	CVCL_6866
	KOCL-51	B acute lymphoblastic leukemia	Homo sapiens	CVCL_6865
	KOCL-69	B acute lymphoblastic leukemia	Homo sapiens	CVCL_3995
	KOPN-1	B acute lymphoblastic leukemia	Homo sapiens	CVCL_3937
	LN-18	Glioblastoma	Homo sapiens	CVCL_0392
	LN-229	Glioblastoma	Homo sapiens	CVCL_0393
	MA9.3 (MA9.3)
	MA9.6ITD (MLL-AF9 plus FLT3-ITD)
	MA9.6RAS (MLL-AF9 plus NRasG12D)
	MA9.6 (MLL-AF9)
	MA9.6ITD (MLL-AF9 plus FLT3-ITD)
	MA9.6RAS (MLL-AF9 plus NRasG12D)
	ME-1 [Human leukemia]	Adult acute myeloid leukemia	Homo sapiens	CVCL_2110
	ML-2	Adult acute myeloid leukemia	Homo sapiens	CVCL_1418
	MV4-11	Childhood acute monocytic leukemia	Homo sapiens	CVCL_0064
	NB4	Acute promyelocytic leukemia	Homo sapiens	CVCL_0005
	NOMO-1	Adult acute monocytic leukemia	Homo sapiens	CVCL_1609
	PL21	Familial adenomatous polyposis	Homo sapiens	CVCL_JM48
	T98G	Glioblastoma	Homo sapiens	CVCL_0556
	THP-1	Childhood acute monocytic leukemia	Homo sapiens	CVCL_0006
	U-87MG ATCC	Glioblastoma	Homo sapiens	CVCL_0022
	U-937	Adult acute monocytic leukemia	Homo sapiens	CVCL_0007
In-vivo Model	For R-2HG injection mouse models, sensitive (NOMO-1 and MA9.3ITD) or resistant (MA9.3RAS) cells were injected into NSGS or NRGS intravenously, and then R-2HG (6mg/kg body weight) or PBS were injected once daily through tail vein for 12 consecutive days starting from day 11 post xeno-transplantation.
Response Summary	This work demonstrates anti-tumor effects of 2HG in inhibiting proliferation/survival of FTO-high cancer cells via targeting FTO/m6A/Myc proto-oncogene protein (MYC)/CEBPA signaling.High levels of FTO sensitize leukemia cells to R-2HG, whereas hyperactivation of MYC signaling confers resistance that can be reversed by the inhibition of MYC signaling. R-2HG also displays anti-tumor activity in glioma. High levels of FTO sensitize leukemic cells to R-2HG, whereas hyperactivation of MYC signaling confers resistance that can be reversed by the inhibition of MYC signaling.
Experiment 2 Reporting the m6A-centered Drug Response of This Target Gene				[9]
Responsed Disease	Leukaemia		ICD-11: 2B33.4	Disease Info
Target Regulation	Down regulation
Cell Process	Glutamine metabolism
Cell Process	Cell apoptosis
In-vitro Model	8-MG-BA	Glioblastoma	Homo sapiens	CVCL_1052
	A-172	Glioblastoma	Homo sapiens	CVCL_0131
	DK-MG	Glioblastoma	Homo sapiens	CVCL_1173
	GaMG	Glioblastoma	Homo sapiens	CVCL_1226
	HEL	Erythroleukemia	Homo sapiens	CVCL_0001
	Jurkat	T acute lymphoblastic leukemia	Homo sapiens	CVCL_0065
	KOCL-45	B acute lymphoblastic leukemia	Homo sapiens	CVCL_3993
	KOCL-48	Childhood acute monocytic leukemia	Homo sapiens	CVCL_6867
	KOCL-50	B acute lymphoblastic leukemia	Homo sapiens	CVCL_6866
	KOCL-51	B acute lymphoblastic leukemia	Homo sapiens	CVCL_6865
	KOCL-69	B acute lymphoblastic leukemia	Homo sapiens	CVCL_3995
	KOPN-1	B acute lymphoblastic leukemia	Homo sapiens	CVCL_3937
	LN-18	Glioblastoma	Homo sapiens	CVCL_0392
	LN-229	Glioblastoma	Homo sapiens	CVCL_0393
	MA9.3 (MA9.3)
	MA9.6ITD (MLL-AF9 plus FLT3-ITD)
	MA9.6RAS (MLL-AF9 plus NRasG12D)
	MA9.6 (MLL-AF9)
	MA9.6ITD (MLL-AF9 plus FLT3-ITD)
	MA9.6RAS (MLL-AF9 plus NRasG12D)
	ME-1 [Human leukemia]	Adult acute myeloid leukemia	Homo sapiens	CVCL_2110
	ML-2	Adult acute myeloid leukemia	Homo sapiens	CVCL_1418
	MV4-11	Childhood acute monocytic leukemia	Homo sapiens	CVCL_0064
	NB4	Acute promyelocytic leukemia	Homo sapiens	CVCL_0005
	NOMO-1	Adult acute monocytic leukemia	Homo sapiens	CVCL_1609
	PL21	Familial adenomatous polyposis	Homo sapiens	CVCL_JM48
	T98G	Glioblastoma	Homo sapiens	CVCL_0556
	THP-1	Childhood acute monocytic leukemia	Homo sapiens	CVCL_0006
	U-87MG ATCC	Glioblastoma	Homo sapiens	CVCL_0022
	U-937	Adult acute monocytic leukemia	Homo sapiens	CVCL_0007
In-vivo Model	For R-2HG injection mouse models, sensitive (NOMO-1 and MA9.3ITD) or resistant (MA9.3RAS) cells were injected into NSGS or NRGS intravenously, and then R-2HG (6mg/kg body weight) or PBS were injected once daily through tail vein for 12 consecutive days starting from day 11 post xeno-transplantation.
Response Summary	This work demonstrates anti-tumor effects of 2HG in inhibiting proliferation/survival of FTO-high cancer cells via targeting FTO/m6A/Myc proto-oncogene protein (MYC)/CEBPA signaling.High levels of FTO sensitize leukemia cells to R-2HG, whereas hyperactivation of MYC signaling confers resistance that can be reversed by the inhibition of MYC signaling. R-2HG also displays anti-tumor activity in glioma. High levels of FTO sensitize leukemic cells to R-2HG, whereas hyperactivation of MYC signaling confers resistance that can be reversed by the inhibition of MYC signaling.

Neutral amino acid transporter B(0) (SLC1A5)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by FTO*
Cell Line	253J cell line	Homo sapiens
Treatment: siFTO 253J cells Control: 253J cells		GSE150239
Regulation		logFC: -1.02E+00 p-value: 5.80E-30
More Results	Click to View More RNA-seq Results

GLS-IN-968 [Investigative]

In total 1 item(s) under this drug			Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene			[41]
Responsed Disease	Renal cell carcinoma	ICD-11: 2C90	Disease Info
Target Regulation	Up regulation
Pathway Response	Central carbon metabolism in cancer		hsa05230
	HIF-1 signaling pathway		hsa04066
	Central carbon metabolism in cancer		hsa05230
	Metabolic pathways		hsa01100
	VEGF signaling pathway		hsa04370
In-vitro Model	UMRC2-vec (CCRCC isogenic cell lines that are VHL-deficient)
Response Summary	Genetic inactivation of FTO using multiple orthogonal approaches revealed that FTO inhibition selectively reduces the growth and survival of VHL-deficient cells in vitro and in vivo. Integrated analysis of transcriptome-wide m6A-seq and mRNA-seq analysis identified the glutamine transporter Neutral amino acid transporter B(0) (SLC1A5) as an FTO target that promotes metabolic reprogramming and survival of VHL-deficient ccRCC cells. GLS1 inhibitors that target mitochondrial glutaminase and the conversion of glutamine to glutamate are currently being evaluated in early-phase clinical trials in ccRCC. These findings identify FTO as a potential HIF-independent therapeutic target for the treatment of VHL-deficient renal cell carcinoma.

PDH kinase 1 (PDK1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by FTO*
Cell Line	NB4 cell line	Homo sapiens
Treatment: shFTO NB4 cells Control: shNS NB4 cells		GSE103494
Regulation		logFC: -7.19E-01 p-value: 8.18E-03
More Results	Click to View More RNA-seq Results

Temozolomide [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[43]
Responsed Disease	Glioblastoma		ICD-11: 2A00.00	Disease Info
Target Regulation	Up regulation
Pathway Response	Citrate cycle			hsa00020
	Central carbon metabolism in cancer			hsa05230
Cell Process	Aerobic glycolysis
	Cell apoptosis
In-vitro Model	LN-18	Glioblastoma	Homo sapiens	CVCL_0392
	LN-229	Glioblastoma	Homo sapiens	CVCL_0393
	SHG-44	Astrocytoma	Homo sapiens	CVCL_6728
	U251 (Fibroblasts or fibroblast like cells)
	U87 (A primary glioblastoma cell line)
Response Summary	Long noncoding RNA just proximal to X-inactive specific transcript facilitates aerobic glycolysis and temozolomide chemoresistance by promoting stability of PDH kinase 1 (PDK1) mRNA in an m6A-dependent manner in glioblastoma multiforme cells. JPX interacted with N6-methyladenosine (m6A) demethylase FTO alpha-ketoglutarate dependent dioxygenase (FTO) and enhanced FTO-mediated PDK1 mRNA demethylation.

Serine/threonine-protein kinase ULK1 (ULK1/ATG1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by FTO*
Cell Line	253J cell line	Homo sapiens
Treatment: siFTO 253J cells Control: 253J cells		GSE150239
Regulation		logFC: -6.13E-01 p-value: 1.25E-06
More Results	Click to View More RNA-seq Results

Cisplatin [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[54]
Responsed Disease	Gastric cancer		ICD-11: 2B72	Disease Info
Target Regulation	Up regulation
In-vitro Model	GES-1	Normal	Homo sapiens	CVCL_EQ22
In-vitro Model	SGC-7901	Gastric carcinoma	Homo sapiens	CVCL_0520
In-vivo Model	A total of 5 × 10⁶ cells in 200 ul PBS were injected subcutaneously into the flanks of nude mice. After injection, cisplatin treatment was initiated on day 5. Mice were injected with 5 mg/kg cisplatin or PBS solution in the abdominal cavity once a week for 3?weeks.
Response Summary	Knockdown of FTO reversed cisplatin resistance of SGC-7901/DDP cells both in vitro and in vivo, which was attributed to the inhibition of Serine/threonine-protein kinase ULK1 (ULK1)-mediated autophagy. These findings indicate that the FTO/ULK1 axis exerts crucial roles in cisplatin resistance of gastric cancer.

Superoxide dismutase [Mn], mitochondrial (SOD2)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by FTO*
Cell Line	NB4 cell line	Homo sapiens
Treatment: shFTO NB4 cells Control: shNS NB4 cells		GSE103494
Regulation		logFC: 8.09E-01 p-value: 6.85E-03
More Results	Click to View More RNA-seq Results

Bortezomib [Approved]

In total 1 item(s) under this drug			Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene			[55]
Responsed Disease	Multiple myeloma	ICD-11: 2A83.1	Disease Info
Target Regulation	Down regulation
Response Summary	FTO promotes Bortezomib resistance via m6A-dependent destabilization of Superoxide dismutase [Mn], mitochondrial (SOD2) expression in multiple myeloma.

Transcription factor SOX-10 (SOX10)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by FTO*
Cell Line	Cerebral cortex	Mus musculus
Treatment: METTL3 (f/f, Emx1-cre) cerebral cortex Control: Wild type cerebral cortex		GSE154992
Regulation		logFC: -8.13E-01 p-value: 2.61E-03
More Results	Click to View More RNA-seq Results

PMID31239444-anti-PD1 antibody [Investigative]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[7]
Responsed Disease	Melanoma		ICD-11: 2C30	Disease Info
Target Regulation	Up regulation
Pathway Response	PD-L1 expression and PD-1 checkpoint pathway in cancer			hsa05235
Cell Process	mRNA decay
In-vitro Model	B16-F10	Mouse melanoma	Mus musculus	CVCL_0159
	CHL-1	Melanoma	Homo sapiens	CVCL_1122
	624-mel	Melanoma	Homo sapiens	CVCL_8054
	NHEM (Normal Human Epidermal Melanocytes)
	SK-MEL-30	Cutaneous melanoma	Homo sapiens	CVCL_0039
	WM115	Melanoma	Homo sapiens	CVCL_0040
	WM35	Melanoma	Homo sapiens	CVCL_0580
	WM3670	Melanoma	Homo sapiens	CVCL_6799
	WM793	Melanoma	Homo sapiens	CVCL_8787
In-vivo Model	When the tumors reached a volume of 80-100 mm³, mice were treated with anti-PD-1 or isotype control antibody (200 ug/mouse) by i.p. injection, every other day for three times. For IFNγ blockade treatment, C57BL/6 mice were treated with anti-IFNγ antibody or isotype control IgG (250 ug/mouse) every other day after tumor cell inoculation.
Response Summary	These findings demonstrate a crucial role of FTO as an m6A demethylase in promoting melanoma tumorigenesis and anti-PD-1 resistance, and suggest that the combination of FTO inhibition with anti-PD-1 blockade reduces the resistance to immunotherapy in melanoma. Knockdown of FTO increases m6A methylation in the critical protumorigenic melanoma cell-intrinsic genes including PD-1 (PDCD1), CXCR4, and Transcription factor SOX-10 (SOX10), leading to increased RNA decay through the m6A reader YTHDF2.

Vascular cell adhesion protein 1 (VCAM1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by FTO*
Cell Line	Mouse hippocampus	Mus musculus
Treatment: FTO knockout mice hippocampus Control: Wild type hippocampus		GSE94098
Regulation		logFC: 6.17E-01 p-value: 3.60E-03
More Results	Click to View More RNA-seq Results

Atorvastatin [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[29]
Responsed Disease	Vascular diseases		ICD-11: BE2Z	Disease Info
Target Regulation	Up regulation
In-vitro Model	THP-1	Childhood acute monocytic leukemia	Homo sapiens	CVCL_0006
	HUVEC-C	Normal	Homo sapiens	CVCL_2959
	HEK293T	Normal	Homo sapiens	CVCL_0063
Response Summary	FTO overexpression significantly upregulated the mRNA and protein levels of Vascular cell adhesion protein 1 (VCAM1) and ICAM-1, downregulated those of KLF2 and eNOS, and strongly attenuated the atorvastatin-mediated induction of KLF2 and eNOS expression. FTO could serve as a novel molecular target to modulate endothelial function in vascular diseases.

Cellular tumor antigen p53 (TP53/p53)

Target Gene

Cisplatin [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[68]
Responsed Disease	Acute kidney failure		ICD-11: GB60	Disease Info
Target Regulation	Down regulation
Pathway Response	Apoptosis			hsa04210
Cell Process	Cell apoptosis
In-vitro Model	HK2	Normal	Acipenser baerii	CVCL_YE28
In-vivo Model	Induced AKI in c57BL/6 mice by intraperitoneal cisplatin injection and treated the animal with vehicle or an FTO inhibitor meclofenamic acid (MA) for 3 days.
Response Summary	Meclofenamic acid increased Cellular tumor antigen p53 (TP53/p53) mRNA and protein levels in AKI both in vitro and in vivo, and FTO overexpression reduced p53 expression and reversed the MA-induced p53 increase in cisplatin-induced acute kidney injury Acute kidney injury.

Meclofenamic acid [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[68]
Responsed Disease	Acute kidney failure		ICD-11: GB60	Disease Info
Target Regulation	Down regulation
Pathway Response	Apoptosis			hsa04210
Cell Process	Cell apoptosis
In-vitro Model	HK2	Normal	Acipenser baerii	CVCL_YE28
In-vivo Model	Induced AKI in c57BL/6 mice by intraperitoneal cisplatin injection and treated the animal with vehicle or an FTO inhibitor meclofenamic acid (MA) for 3 days.
Response Summary	Meclofenamic acid increased Cellular tumor antigen p53 (TP53/p53) mRNA and protein levels in AKI both in vitro and in vivo, and FTO overexpression reduced p53 expression and reversed the MA-induced p53 increase in cisplatin-induced Acute kidney injury.

Constitutive NOS (eNOS)

Target Gene

Atorvastatin [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[29]
Responsed Disease	Vascular diseases		ICD-11: BE2Z	Disease Info
Target Regulation	Down regulation
In-vitro Model	THP-1	Childhood acute monocytic leukemia	Homo sapiens	CVCL_0006
	HUVEC-C	Normal	Homo sapiens	CVCL_2959
	HEK293T	Normal	Homo sapiens	CVCL_0063
Response Summary	FTO overexpression significantly upregulated the mRNA and protein levels of VCAM-1 and ICAM-1, downregulated those of KLF2 and Constitutive NOS (eNOS), and strongly attenuated the atorvastatin-mediated induction of KLF2 and eNOS expression. FTO could serve as a novel molecular target to modulate endothelial function in vascular diseases.

Mammalian target of rapamycin complex 1 (mTORC1)

Target Gene

Cisplatin [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[19]
Responsed Disease	Gastric cancer		ICD-11: 2B72	Disease Info
Target Regulation	Down regulation
Pathway Response	mTOR signaling pathway			hsa04150
Cell Process	Cell apoptosis
In-vitro Model	AGS	Gastric adenocarcinoma	Homo sapiens	CVCL_0139
In-vitro Model	HGC-27	Gastric carcinoma	Homo sapiens	CVCL_1279
Response Summary	Omeprazole pretreatment could enhance the inhibitory effect of 5-Fu, DDP and TAX on gastric cancer cells. FTO inhibition induced by omeprazole enhanced the activation of Mammalian target of rapamycin complex 1 (mTORC1) signal pathway that inhibited the prosurvival autophagy so as to improve the antitumor efficiency of chemotherapeutic drugs on GC cells. Meanwhile, transcript level of DDIT3, which is an apoptosis-related tumor suppressor gene downstream of mTORC1, was regulated by omeprazole-induced FTO silence through an m6A-dependent mechanism. m6A modification and its eraser FTO plays a role in the improvement of chemosensitivity mediated by proton pump inhibitor omeprazole.

Fluorouracil [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[19]
Responsed Disease	Gastric cancer		ICD-11: 2B72	Disease Info
Target Regulation	Down regulation
Pathway Response	mTOR signaling pathway			hsa04150
Cell Process	Cell apoptosis
In-vitro Model	AGS	Gastric adenocarcinoma	Homo sapiens	CVCL_0139
In-vitro Model	HGC-27	Gastric carcinoma	Homo sapiens	CVCL_1279
Response Summary	Omeprazole pretreatment could enhance the inhibitory effect of 5-Fu, DDP and TAX on gastric cancer cells. FTO inhibition induced by omeprazole enhanced the activation of Mammalian target of rapamycin complex 1 (mTORC1) signal pathway that inhibited the prosurvival autophagy so as to improve the antitumor efficiency of chemotherapeutic drugs on GC cells. Meanwhile, transcript level of DDIT3, which is an apoptosis-related tumor suppressor gene downstream of mTORC1, was regulated by omeprazole-induced FTO silence through an m6A-dependent mechanism. m6A modification and its eraser FTO plays a role in the improvement of chemosensitivity mediated by proton pump inhibitor omeprazole.

Paclitaxel [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[19]
Responsed Disease	Gastric cancer		ICD-11: 2B72	Disease Info
Target Regulation	Down regulation
Pathway Response	mTOR signaling pathway			hsa04150
Cell Process	Cell apoptosis
In-vitro Model	AGS	Gastric adenocarcinoma	Homo sapiens	CVCL_0139
In-vitro Model	HGC-27	Gastric carcinoma	Homo sapiens	CVCL_1279
Response Summary	Omeprazole pretreatment could enhance the inhibitory effect of 5-Fu, DDP and TAX on gastric cancer cells. FTO inhibition induced by omeprazole enhanced the activation of Mammalian target of rapamycin complex 1 (mTORC1) signal pathway that inhibited the prosurvival autophagy so as to improve the antitumor efficiency of chemotherapeutic drugs on GC cells. Meanwhile, transcript level of DDIT3, which is an apoptosis-related tumor suppressor gene downstream of mTORC1, was regulated by omeprazole-induced FTO silence through an m6A-dependent mechanism. m6A modification and its eraser FTO plays a role in the improvement of chemosensitivity mediated by proton pump inhibitor omeprazole.

Programmed cell death 1 (PD-1)

Target Gene

PMID31239444-anti-PD1 antibody [Investigative]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[7]
Responsed Disease	Melanoma		ICD-11: 2C30	Disease Info
Target Regulation	Up regulation
Pathway Response	PD-L1 expression and PD-1 checkpoint pathway in cancer			hsa05235
Cell Process	mRNA decay
In-vitro Model	B16-F10	Mouse melanoma	Mus musculus	CVCL_0159
	CHL-1	Melanoma	Homo sapiens	CVCL_1122
	624-mel	Melanoma	Homo sapiens	CVCL_8054
	NHEM (Normal Human Epidermal Melanocytes)
	SK-MEL-30	Cutaneous melanoma	Homo sapiens	CVCL_0039
	WM115	Melanoma	Homo sapiens	CVCL_0040
	WM35	Melanoma	Homo sapiens	CVCL_0580
	WM3670	Melanoma	Homo sapiens	CVCL_6799
	WM793	Melanoma	Homo sapiens	CVCL_8787
In-vivo Model	When the tumors reached a volume of 80-100 mm³, mice were treated with anti-PD-1 or isotype control antibody (200 ug/mouse) by i.p. injection, every other day for three times. For IFNγ blockade treatment, C57BL/6 mice were treated with anti-IFNγ antibody or isotype control IgG (250 ug/mouse) every other day after tumor cell inoculation.
Response Summary	These findings demonstrate a crucial role of FTO as an m6A demethylase in promoting melanoma tumorigenesis and anti-PD-1 resistance, and suggest that the combination of FTO inhibition with anti-PD-1 blockade reduces the resistance to immunotherapy in melanoma. Knockdown of FTO increases m6A methylation in the critical protumorigenic melanoma cell-intrinsic genes including Programmed cell death 1 (PD-1) (PDCD1), CXCR4, and SOX10, leading to increased RNA decay through the m6A reader YTHDF2.

Retinoic acid receptor alpha (RARA)

Target Gene

Tretinoin [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[2]
Responsed Disease	Acute myeloid leukaemia		ICD-11: 2A60	Disease Info
Target Regulation	Down regulation
Cell Process	RNA stability
Cell Process	RNA degradation (hsa03018)
In-vitro Model	K-562	Chronic myelogenous leukemia	Homo sapiens	CVCL_0004
	KOCL-48	Childhood acute monocytic leukemia	Homo sapiens	CVCL_6867
	Mono-Mac-6	Adult acute monocytic leukemia	Homo sapiens	CVCL_1426
Response Summary	FTO enhances leukemic oncogene-mediated cell transformation and leukemogenesis, and inhibits all-trans-retinoic acid (ATRA)-induced AML cell differentiation, through regulating expression of targets such as ASB2 and Retinoic acid receptor alpha (RARA) by reducing m6A levels in these mRNA transcripts.

Serine/threonine-protein kinase mTOR (MTOR)

Target Gene

Asparagine inhibitor [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[12]
Responsed Disease	Colorectal cancer		ICD-11: 2B91	Disease Info
Pathway Response	mTOR signaling pathway			hsa04150
	Autophagy			hsa04140
Cell Process	RNA decay
	Cell growth and death
	Cell autophagy
In-vitro Model	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
Response Summary	In colorectal cancer, Glutaminolysis inhibition upregulated ATF4 expression in an m6A-dependent manner to activate pro-survival autophagy through transcriptional activation of the mTOR inhibitor DDIT4. Determined the relationship between FTO alpha-ketoglutarate dependent dioxygenase (FTO), YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), and ATF4. ATF4 transcriptionally upregulated DDIT4 to suppress Serine/threonine-protein kinase mTOR (MTOR), which induced pro-survival autophagy during glutaminolysis inhibition.

Chloroquine [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[12]
Responsed Disease	Colorectal cancer		ICD-11: 2B91	Disease Info
Pathway Response	mTOR signaling pathway			hsa04150
	Autophagy			hsa04140
Cell Process	RNA decay
	Cell growth and death
	Cell autophagy
In-vitro Model	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
Response Summary	In colorectal cancer, Glutaminolysis inhibition upregulated ATF4 expression in an m6A-dependent manner to activate pro-survival autophagy through transcriptional activation of the mTOR inhibitor DDIT4. Determined the relationship between FTO alpha-ketoglutarate dependent dioxygenase (FTO), YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), and ATF4. ATF4 transcriptionally upregulated DDIT4 to suppress Serine/threonine-protein kinase mTOR (MTOR), which induced pro-survival autophagy during glutaminolysis inhibition.

Meclofenamate sodium [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[12]
Responsed Disease	Colorectal cancer		ICD-11: 2B91	Disease Info
Pathway Response	mTOR signaling pathway			hsa04150
	Autophagy			hsa04140
Cell Process	RNA decay
	Cell growth and death
	Cell autophagy
In-vitro Model	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
Response Summary	In colorectal cancer, Glutaminolysis inhibition upregulated ATF4 expression in an m6A-dependent manner to activate pro-survival autophagy through transcriptional activation of the mTOR inhibitor DDIT4. Determined the relationship between FTO alpha-ketoglutarate dependent dioxygenase (FTO), YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), and ATF4. Serine/threonine-protein kinase mTOR (MTOR) transcriptionally upregulated DDIT4 to suppress mTOR, which induced pro-survival autophagy during glutaminolysis inhibition.

Rapamycin [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[12]
Responsed Disease	Colorectal cancer		ICD-11: 2B91	Disease Info
Pathway Response	mTOR signaling pathway			hsa04150
	Autophagy			hsa04140
Cell Process	RNA decay
	Cell growth and death
	Cell autophagy
In-vitro Model	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
Response Summary	In colorectal cancer, Glutaminolysis inhibition upregulated ATF4 expression in an m6A-dependent manner to activate pro-survival autophagy through transcriptional activation of the mTOR inhibitor DDIT4. Determined the relationship between FTO alpha-ketoglutarate dependent dioxygenase (FTO), YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), and ATF4. Serine/threonine-protein kinase mTOR (MTOR) transcriptionally upregulated DDIT4 to suppress mTOR, which induced pro-survival autophagy during glutaminolysis inhibition.

CB-839 [Phase 2]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[12]
Responsed Disease	Colorectal cancer		ICD-11: 2B91	Disease Info
Pathway Response	mTOR signaling pathway			hsa04150
	Autophagy			hsa04140
Cell Process	RNA decay
	Cell growth and death
	Cell autophagy
In-vitro Model	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
Response Summary	In colorectal cancer, Glutaminolysis inhibition upregulated ATF4 expression in an m6A-dependent manner to activate pro-survival autophagy through transcriptional activation of the mTOR inhibitor DDIT4. Determined the relationship between FTO alpha-ketoglutarate dependent dioxygenase (FTO), YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), and ATF4. Serine/threonine-protein kinase mTOR (MTOR) transcriptionally upregulated DDIT4 to suppress mTOR, which induced pro-survival autophagy during glutaminolysis inhibition.

GLS-IN-968 [Investigative]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[12]
Responsed Disease	Colorectal cancer		ICD-11: 2B91	Disease Info
Pathway Response	mTOR signaling pathway			hsa04150
	Autophagy			hsa04140
Cell Process	RNA decay
	Cell growth and death
	Cell autophagy
In-vitro Model	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
Response Summary	In colorectal cancer, Glutaminolysis inhibition upregulated ATF4 expression in an m6A-dependent manner to activate pro-survival autophagy through transcriptional activation of the mTOR inhibitor DDIT4. Determined the relationship between FTO alpha-ketoglutarate dependent dioxygenase (FTO), YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), and ATF4. ATF4 transcriptionally upregulated DDIT4 to suppress Serine/threonine-protein kinase mTOR (MTOR), which induced pro-survival autophagy during glutaminolysis inhibition.

Signal transducer and activator of transcription 3 (STAT3)

Target Gene

Doxil [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[89]
Responsed Disease	Breast cancer		ICD-11: 2C60	Disease Info
In-vitro Model	MDA-MB-231	Breast adenocarcinoma	Homo sapiens	CVCL_0062
	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
	Hs 578T	Invasive breast carcinoma	Homo sapiens	CVCL_0332
Response Summary	Decreased doxorubicin resistance by Signal transducer and activator of transcription 3 (STAT3) knockdown was abolished by FTO overexpression and decreased doxorubicin sensitivity by STAT3 overexpression was reversed by FTO knockdown, indicating that FTO was implicated in STAT3-mediated doxorubicin resistance and impairment of doxorubicin sensitivity of BC cells.

Ubiquitin carboxyl-terminal hydrolase 7 (USP7)

Target Gene

P22077 [Investigative]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[91]
Responsed Disease	Non-small-cell lung carcinoma		ICD-11: 2C25.Y	Disease Info
Target Regulation	Up regulation
Cell Process	Ubiquitination degradation
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	NCI-H522	Lung adenocarcinoma	Homo sapiens	CVCL_1567
	HSAEC (Human small airway epithelial cells)
	RERF-LC-A1	Lung squamous cell carcinoma	Homo sapiens	CVCL_4402
	NCI-H1882	Lung small cell carcinoma	Homo sapiens	CVCL_1504
	NCl-H466 (Human lung cancer cell line)
In-vivo Model	Equal numbers of A549 cells expressing either control or shFTO were injected subcutaneously, within 30 min of harvesting, over the right and left flanks in male nu/nu mice between 4 and 6 weeks of age.
Response Summary	The m6A demethylase FTO promotes the growth of Non-small cell lung cancer cells by increasing the expression of USP7.Genetic knockdown or pharmacological inhibition (P5091 or P22027) of Ubiquitin carboxyl-terminal hydrolase 7 (USP7) reduced the proliferation rate of lung cancer cells and decreased the capacity of colony formation of lung cancer cells in vitro, whereas lung cancer cells growth inhibition by FTO knockdown is restored by overexertion of USP7.

P5091 [Investigative]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[91]
Responsed Disease	Non-small-cell lung carcinoma		ICD-11: 2C25.Y	Disease Info
Target Regulation	Up regulation
Cell Process	Ubiquitination degradation
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	NCI-H522	Lung adenocarcinoma	Homo sapiens	CVCL_1567
	HSAEC (Human small airway epithelial cells)
	RERF-LC-A1	Lung squamous cell carcinoma	Homo sapiens	CVCL_4402
	NCI-H1882	Lung small cell carcinoma	Homo sapiens	CVCL_1504
	NCl-H466 (Human lung cancer cell line)
In-vivo Model	Equal numbers of A549 cells expressing either control or shFTO were injected subcutaneously, within 30 min of harvesting, over the right and left flanks in male nu/nu mice between 4 and 6 weeks of age.
Response Summary	The m6A demethylase FTO promotes the growth of Non-small cell lung cancer cells by increasing the expression of USP7.Genetic knockdown or pharmacological inhibition (P5091 or P22027) of Ubiquitin carboxyl-terminal hydrolase 7 (USP7) reduced the proliferation rate of lung cancer cells and decreased the capacity of colony formation of lung cancer cells in vitro, whereas lung cancer cells growth inhibition by FTO knockdown is restored by overexertion of USP7.

microRNA 155 (MIR155)

Target Gene

Temozolomide [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[94]
Responsed Disease	Glioma		ICD-11: 2A00.0	Disease Info
In-vitro Model	A-172	Glioblastoma	Homo sapiens	CVCL_0131
	HEK293T	Normal	Homo sapiens	CVCL_0063
	U251 (Fibroblasts or fibroblast like cells)
	U87 (A primary glioblastoma cell line)
In-vivo Model	Previously prepared U87 cells (5 × 10⁶ cells, 60 uL) stably infected with miRNA were injected subcutaneously in the right flank of the mice, whereas control U87 cells infected with empty vector were injected in the left flank.
Response Summary	FTO Inhibition Enhances the Antitumor Effect of Temozolomide by Targeting MYC-microRNA 155 (MIR155)/miR-23a Cluster-MXI1 Feedback Circuit in Glioma.

microRNA 23a (MIR23A)

Target Gene

Temozolomide [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[94]
Responsed Disease	Glioma		ICD-11: 2A00.0	Disease Info
In-vitro Model	A-172	Glioblastoma	Homo sapiens	CVCL_0131
	HEK293T	Normal	Homo sapiens	CVCL_0063
	U251 (Fibroblasts or fibroblast like cells)
	U87 (A primary glioblastoma cell line)
In-vivo Model	Previously prepared U87 cells (5 × 10⁶ cells, 60 uL) stably infected with miRNA were injected subcutaneously in the right flank of the mice, whereas control U87 cells infected with empty vector were injected in the left flank.
Response Summary	FTO Inhibition Enhances the Antitumor Effect of Temozolomide by Targeting MYC-miR-155/microRNA 23a (MIR23A) Cluster-MXI1 Feedback Circuit in Glioma.

Unspecific Target Gene

Arsenite [Phase 2]

In total 2 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[97]
Cell Process	Cell apoptosis
In-vitro Model	HBE (Human bronchial epithelial cell line)
Response Summary	m6A modification on RNA was significantly increased in arsenite-transformed cells and this modification was synergistically regulated by METTL3, METTL14, WTAP and FTO. Demonstrated the significant role of m6A in the prevention of tumor occurrence and progression induced by arsenite.
Experiment 2 Reporting the m6A-centered Drug Response of This Target Gene				[126]
Responsed Disease	Neurological disorders due to toxicity		ICD-11: 8D43	Disease Info
In-vitro Model	PC-12 Adh	Rat adrenal gland pheochromocytoma	Rattus norvegicus	CVCL_F659
In-vivo Model	The animals were kept in standard laboratory polycarbonate cages in controlled ambient temperature at 23℃ ± 1℃ with relative humidity of 50% ± 10%, and a light-dark cycle of 12/12 h. The mice had free access to standardized pellet food and tap water. After 1-week of habituation, the animals were randomly divided into the following 4 groups: control group, 0.5 mg/l arsenite group, 5 mg/l arsenite group and 50 mg/l arsenite group (n = 16 per group). The mice were exposed to arsenite via drinking water for 6 months.
Response Summary	targeting the m6A demethylase FTO in the prevention or intervention against arsenite-related neurodegenerative diseases.

Saikosaponins [Investigative]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[102]
Responsed Disease	Acute myeloid leukaemia		ICD-11: 2A60	Disease Info
Cell Process	Cell apoptosis
Cell Process	Cell-cycle
In-vitro Model	C1498	Mouse leukemia	Mus musculus	CVCL_3494
	HL-60	Adult acute myeloid leukemia	Homo sapiens	CVCL_0002
	K-562	Chronic myelogenous leukemia	Homo sapiens	CVCL_0004
	Kasumi-1	Myeloid leukemia with maturation	Homo sapiens	CVCL_0589
	MOLM-13	Adult acute myeloid leukemia	Homo sapiens	CVCL_2119
	MOLM-14	Adult acute myeloid leukemia	Homo sapiens	CVCL_7916
	MV4-11	Childhood acute monocytic leukemia	Homo sapiens	CVCL_0064
	NB4	Acute promyelocytic leukemia	Homo sapiens	CVCL_0005
	SKNO-1	Myeloid leukemia with maturation	Homo sapiens	CVCL_2196
	U-937	Adult acute monocytic leukemia	Homo sapiens	CVCL_0007
In-vivo Model	Upon the development of leukemic disease (established using a white blood cell (WBC) count), 0.1 mg/kg or 0.5 mg/kg of SsD was intraperitoneally injected three times per week for three consecutive weeks.
Response Summary	FTO-dependent m6A RNA methylation mediated the anti-leukemic actions of saikosaponin-d, thereby opening a window to develop SsD as an epitranscriptome-base drug for leukemia therapy. SsD showed a broadly-suppressed acute myeloid leukemia cell proliferation and promoted apoptosis and cell-cycle arrest both in vitro and in vivo.

Cisplatin [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[127]
Responsed Disease	Ototoxic hearing loss		ICD-11: AB53	Disease Info
Cell Process	Oxidative stress
	Cell autophagy
In-vitro Model	HEI-OC1	Normal	Mus musculus	CVCL_D899
Response Summary	MA2, which is a highly selective inhibitor of FTO, has a protective effect and improves the viability of HEI-OC1 cells after cisplatin treatment, and they provide new insights into potential therapeutic targets for the amelioration of cisplatin-induced ototoxicity.

Sunitinib [Approved]

In total 1 item(s) under this drug			Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene			[131]
Responsed Disease	Diseases of the circulatory system	ICD-11: BE2Z	Disease Info
In-vitro Model	hiPSCs (Urinary epithelial cell-derived hiPSCs)
	CMECs (Cardiac Microvascular Endothelial Cells )
	CFs (Cardiac Fibroblasts)
Response Summary	The RNA demethylase FTO was downregulated, whereas METTL14 and WTAP were upregulated. Furthermore, gain- and loss-of-function studies substantiated that FTO is cardioprotective in TKI(Sunitinib).

Betaine [Approved]

In total 1 item(s) under this drug			Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene			[132]
Responsed Disease	Non-alcoholic fatty liver disease	ICD-11: DB92	Disease Info
In-vivo Model	Eight adult female C57BL/6 mice from the same pool of litters were housed at 22 ± 1 ℃ with 12-h light cycle and were mated with their male siblings. The female mice were fed with a low-fat diet supplemented with betaine from mating and throughout gestation and lactation. Litters were culled to five males per dam. Thirty offspring weaned at the age of day 21 and then were randomly assigned to three groups fed with either a low-fat diet (LF), high-fat diet (HF), or high-fat diet supplemented with betaine (HB) for 6 weeks.
Response Summary	A novel FTO-dependent function of m(6)A is involve in the hepatoprotective effects of betaine. betaine supplementation across adolescence could protect mice from high-fat-induced lipid accumulation NAFLD in the liver. Moreover, FTO-dependent m6A demethylation is affected by betaine. A novel FTO-dependent function of m(6)A may involve in the hepatoprotective effects of betaine.

Click to View Potential Drug Response of This Regulator

Xenobiotics Compound(s) Regulating the m6A Methylation Regulator

Compound Name	MA2	Approved
Synonyms	Ethyl ester form of meclofenamic acid (MA) Click to Show/Hide
Description	MA2, which is a highly selective inhibitor of FTO, has a protective effect and improves the viability of HEI-OC1 cells after cisplatin treatment, and they provide new insights into potential therapeutic targets for the amelioration of cisplatin-inducedototoxicity.	[127]
Compound Name	Rapamycin	Approved
Synonyms	Rapamune; Rapamycin (Sirolimus); AY-22989; Rapammune; sirolimusum; WY-090217; RAPA; Antibiotic AY 22989; AY 22989; UNII-W36ZG6FT64; CCRIS 9024; CHEBI:9168; SILA 9268A; W36ZG6FT64; HSDB 7284; C51H79NO13; NSC 226080; DE-109; NCGC00021305-05; DSSTox_CID_3582; DSSTox_RID_77091; DSSTox_GSID_23582; Cypher; Supralimus; Wy 090217; Perceiva; RAP; RPM; Rapamycin from Streptomyces hygroscopicus; SIIA 9268A; LCP-Siro; MS-R001; Rapamune (TN); Rapamycin (TN); Sirolimus (RAPAMUNE); Rapamycin C-7, analog 4; Sirolimus (USAN/INN); Sirolimus [USAN:BAN:INN]; Sirolimus, Rapamune,Rapamycin; Heptadecahydro-9,27-dihydroxy-3-[(1R)-2-[(1S,3R,4R)-4-hydroxy; 23,27-Epoxy-3H-pyrido(2,1-c)(1,4)oxaazacyclohentriacontine; 23,27-Epoxy-3H-pyrido[2,1-c][1,4]oxaazacyclohentriacontine; 23,27-epoxy-3H-pyrido[2,1-c][1,4]oxaazacyclohentriacontine-1,5,11,28,29; 3H-pyrido(2,1-c)(1,4)oxaazacyclohentriacontine-1,5,11,28,29(4H,6H,31H)-pentone; Sirolimus (MTOR inhibitor) Click to Show/Hide
External link	CID: 5284616 TTD: D03LJR DrugBank: DB00877
Description	The m6A changes caused by FTO influence the stability of ULK1 transcripts, likely through a YTHDF2-dependent manner.Under both basal and rapamycin-induced autophagy conditions, depletion of FTO significantly reduced the formation of GFP-LC3B puncta. The level ofp62/SQSTM1 (an autophagy substrate) was higher in FTO-knockdown cells than that in control cells. FTO specifically upregulates the ULK1 protein abundance. ULK1 mRNA undergoes m6A modification in the 3'-UTR and the m6A-marked ULK1 transcripts can further be targeted for degradation by YTHDF2.	[138]
Compound Name	Meclofenamic Acid	Approved
Synonyms	Arquel; Meclofenamate; Acide meclofenamique; Acido meclofenamico; Acidum meclofenamicum; Meclophenamic acid; CL 583; INF 4668; Acide meclofenamique [INN-French]; Acido meclofenamico [INN-Spanish]; Acidum meclofenamicum [INN-Latin]; INF-4668; Meclomen (free acid); Meclofenamic acid (USAN/INN); Meclofenamic acid [USAN:INN:BAN]; N-(2,6-Dichloro-3-methylphenyl)anthranilic acid; N-(2,6-Dichloro-m-tolyl)anthranilic acid; N-(3-Methyl-2,6-dichlorophenyl)anthranilic acid; 2-((2,6-Dichloro-3-methylphenyl)amino)benzoic acid; 2-(2,6-Dichloro-3-methylphenyl)aminobenzoic acid; 2-(2,6-dichloro-3-methylanilino)benzoic acid; 2-[(2,6-dichloro-3-methylphenyl)amino]benzoic acid Click to Show/Hide
External link	CID: 4037 TTD: D08IFL DrugBank: DB00939
Description	Genetic depletion and pharmacological inhibition of FTO dramatically attenuate leukemia stem/initiating cell self-renewal and reprogram immune response by suppressing expression of immune checkpoint genes, especiallyLILRB4. FTO inhibitors, such as rhein, meclofenamic acid (MA), MO-I-500, fluorescein, and R-2HG, can inhibitacute myeloid leukemia cell viability. CS1 and CS2 displayed a much higher efficacy in inhibiting AML cell viability.	[30]
Compound Name	Fluorescite	Approved
Synonyms	Funduscein-25; Ak-fluor 10%; Ak-fluor 25%; Fluorescite Click to Show/Hide
External link	CID: 16850 TTD: D07FUJ DrugBank: DB00693
Description	Genetic depletion and pharmacological inhibition of FTO dramatically attenuate leukemia stem/initiating cell self-renewal and reprogram immune response by suppressing expression of immune checkpoint genes, especiallyLILRB4. FTO inhibitors, such as rhein, meclofenamic acid (MA), MO-I-500, fluorescein, and R-2HG, can inhibitacute myeloid leukemia cell viability. CS1 and CS2 displayed a much higher efficacy in inhibiting AML cell viability.	[30]
Compound Name	Comtan	Approved
Synonyms	Comtan; Comtess; Entacapona; Entacaponum; Novartis brand of entacapone; Orion brand of entacapone; KB475572; OR 611; COM-998; Comtan (TN); Entacapona [INN-Spanish]; Entacapone [USAN:INN]; Entacaponum [INN-Latin]; OR-611; Stalevo (TN); Entacapone (JAN/USAN/INN); N,N-diethyl-2-cyano-3-(3,4-dihydroxy-5-nitrophenyl) acrylamide; (2E)-2-cyano-3-(3,4-dihydroxy-5-nitrophenyl)-N,N-diethylprop-2-enamide; (E)-2-Cyano-3-(3,4-dihydroxy-5-nitrophenyl)-N,N-diethyl-2-propenamide; (E)-2-cyano-3-(3,4-dihydroxy-5-nitro-phenyl)-N,N-diethyl-prop-2-enamide; (E)-2-cyano-3-(3,4-dihydroxy-5-nitrophenyl)-N,N-diethylprop-2-enamide; (E)-alpha-Cyano-N,N-diethyl-3,4-dihydroxy-5-nitrocinnamamide; 2-Cyano-N,N-diethyl-3-(3,4-dihydroxy-5-nitrophenyl)propenamide Click to Show/Hide
External link	CID: 5281081 TTD: D0J1VY DrugBank: DB00494
Description	Studies of the aberrant expression of m6A mediators inbreast cancer revealed that they were associated with different BC subtypes and functions, such as proliferation, apoptosis, stemness, the cell cycle, migration, and metastasis, through several factors and signaling pathways, such asBcl-2 and the PI3K/Akt pathway, among others. Fat mass and obesity-associated protein (FTO) was identified as the first m6A demethylase, and a series of inhibitors that target FTO were reported to have potential for the treatment of BC by inhibiting cell proliferation and promoting apoptosis.	[4]
Compound Name	Berberine	Phase 4
Synonyms	Berberin; Umbellatine; UNII-0I8Y3P32UF; 0I8Y3P32UF; CHEBI:16118; EINECS 218-229-1; Berberal; BRN 3570374; ST055798; 9,10-Dimethoxy-2,3-(methylenedioxy)-7,8,13,13a-tetrahydroberbinium; Benzo(g)-1,3-benzodioxolo(5,6-a)quinolizinium, 5,6-dihydro-9,10-dimethoxy-; 9,10-dimethoxy-5,6-dihydro[1,3]dioxolo[4,5-g]isoquino[3,2-a]isoquinolin-7-ium; Berbamine sulphate acid; CHEMBL12089; 7,8,13,13a-tetradehydro-9,10-dimethoxy-2,3-(methylenedioxy)berbinium; BERBINIUM, 7,8,13,13a-TETRAHYDRO-9,10-DIMETHOXY-2,3-(METHYLE Click to Show/Hide
External link	CID: 2353 TTD: D0W8WB DrugBank: DB04115
Description	Berberine effectively decreased m6A methylation by decreasing beta-catenin and subsequently increased FTO suggests a role of Berberine in modulating stemness and malignant behaviors incolorectal cancer.	[110]
Compound Name	Bisantrene	Phase 3
Synonyms	Bisantrenum; CL 216942; CHEMBL25336; NSC 337766; 39C34M111K; N-[(E)-[10-[(E)-(4,5-dihydro-1H-imidazol-2-ylhydrazinylidene)methyl]anthracen-9-yl]methylideneamino]-4,5-dihydro-1H-imidazol-2-amine; 9,10-Bis((2-(4,5-dihydro-1H-imidazol-2-yl)hydrazono)methyl)anthracene; Bisantrene [INN]; Bisantrenum [INN-Latin]; 9,10-Bis(2-(4,5-dihydro-1H-imidazol-2-yl)hydrazono)methyl)anthracene; Bisantreno [INN-Spanish]; NSC337766; NSC-337766; BRN 0966309; 9,10-Anthracenedicarboxaldehyde, bis((4,5-dihydro-1H-imidazol-2-yl)hydrazone)-; 9,10-Anthracendicarbaldehyde bis(2-imidazolin-2-ylhydrazon); 9,10-Anthracenedicarboxaldehyde, bis[(4,5-dihydro-1H-imidazol-2-yl)hydrazone], dihydrochloride; SCHEMBL8906393; 9,10-bis((E)-(2-(4,5-dihydro-1H-imidazol-2-yl)hydrazono)methyl)anthracene; EX-A2382; ZINC1550957; BDBM50060768; CCG-35603; MFCD01743164; CS-6132; AS-75775; N-[(E)-[10-[(E)-(4,5-dihydro-1H-imidazol-2-ylhydrazono)methyl]-9-anthryl]methyleneamino]-4,5-dihydro-1H-imidazol-2-amine; HY-100875; 186B342; BRD-K64298650-300-01-5; 9,10-Anthracenedicarboxaldehyde Bis(2-imidazolin-2-yl-hydrazone); 9,10-Anthracenedicarbaldehyde bis(4,5-dihydro-1H-imidazol-2-ylhydrazone); anthracene-9,10 bis-carbaldehyde 4,5-dihydro-1H-imidazol-2-ylhydrazone; 9,10-anthracenedicarboxaldehyde Bis[(4,5-dihydro-1H-imidazol-2yl)hydrazone); 9,10-Anthracenedicarboxaldehyde, bis(4,5-dihydro-1H-imidazol-2-ylhydrazone),dihydrochloride; N-Anthracen-9-yl methylene N''-[(bis)4,5-dihydro-1H-imidazole-2-yl)-hydrazine; N-Anthracen-bis-9,10-ylmethylene-N''-(4,5-dihydro-1H-imidazol-2-yl)-hydrazine(bisantrene); 10-imino(4,5-dihydro-1H-2-imidazolamine)methyl-9-anthrylmethan-(4,5-dihydro-1H-2-imidazolamine)imine; Bis((4,5-dihydro-1H-imidazol-2-yl)hydrazone)-9,10-anthracenedicarboxaldehyde dihydrochloride; x N-4,5-dihydro-1H-2-imidazolamine-10-iminomethyl-9-anthrylmethanimine-4,5-dihydro-1H-2-imidazolamine (Bisantrene) Click to Show/Hide
External link	CID: 5351322
Description	Genetic depletion and pharmacological inhibition of FTO dramatically attenuate leukemia stem/initiating cell self-renewal and reprogram immune response by suppressing expression of immune checkpoint genes, especiallyLILRB4. FTO inhibitors, such as rhein, meclofenamic acid (MA), MO-I-500, fluorescein, and R-2HG, can inhibitacute myeloid leukemia cell viability. CS1 and CS2 displayed a much higher efficacy in inhibiting AML cell viability.	[30]
Compound Name	Brequinar	Phase 2
Synonyms	6-Fluoro-2-(2'-fluoro-[1,1'-biphenyl]-4-yl)-3-methylquinoline-4-carboxylic acid; brequinarum [Latin]; Brequinar [INN]; Biphenquinate; 6-fluoro-2-(2'-fluorobiphenyl-4-yl)-3-methylquinoline-4-carboxylic acid; Brequinarum [INN-Latin]; UNII-5XL19F49H6; C23H15F2NO2; NSC-368390; NSC 368390; 6-fluoro-2-[4-(2-fluorophenyl)phenyl]-3-methylquinoline-4-carboxylic acid; PHEZJEYUWHETKO-UHFFFAOYSA-N; Dup 785; 5XL19F49H6; 6-FLUORO-2-(2'-FLUORO-1,1'-BIPHENYL-4-YL)-3-METHYLQUINOLINE-4-CARBOXYLIC ACID; brequinarum Click to Show/Hide
External link	CID: 57030 TTD: D0N3XT DrugBank: DB03523
Description	Genetic depletion and pharmacological inhibition of FTO dramatically attenuate leukemia stem/initiating cell self-renewal and reprogram immune response by suppressing expression of immune checkpoint genes, especiallyLILRB4. FTO inhibitors, such as rhein, meclofenamic acid (MA), MO-I-500, fluorescein, and R-2HG, can inhibitacute myeloid leukemia cell viability. CS1 and CS2 displayed a much higher efficacy in inhibiting AML cell viability.	[30]
Compound Name	3DZA	Terminated
Synonyms	Cc3Ado; BW-91Y78; 3DZA; 4-Amino-1-beta-D-ribofuranosyl-1H-imidazo[4,5-c]pyridine Click to Show/Hide
External link	CID: 23190 TTD: D0I7TN
Description	Studies of the aberrant expression of m6A mediators inbreast cancer revealed that they were associated with different BC subtypes and functions, such as proliferation, apoptosis, stemness, the cell cycle, migration, and metastasis, through several factors and signaling pathways, such asBcl-2 and the PI3K/Akt pathway, among others. Fat mass and obesity-associated protein (FTO) was identified as the first m6A demethylase, and a series of inhibitors that target FTO were reported to have potential for the treatment of BC by inhibiting cell proliferation and promoting apoptosis.	[4]
Compound Name	FB23	Investigative
Synonyms	FB23; 2243736-35-6; 2-[[2,6-bis(chloranyl)-4-(3,5-dimethyl-1,2-oxazol-4-yl)phenyl]amino]benzoic acid; CHEMBL4572939; SCHEMBL23261118; BCP33227; EX-A3402; FB-23;FB 23; s6291; HY-137187; CS-0136974; A936869; 2-[[2,6-Dichloro-4-(3,5-dimethyl-4-isoxazolyl)phenyl]amino]benzoic acid; 8S3 Click to Show/Hide
External link	CID: 138393314
Activity	IC50 = 60 nM	[139]
Compound Name	(Z)-3-(3,4-dihydroxy-5-nitrophenyl)-2-pyrazin-2-ylprop-2-enenitrile	Investigative
Synonyms	CHEMBL4448030; SCHEMBL20100848 Click to Show/Hide
External link	CID: 137283544
Activity	IC50 <= 250 nM	[140]
Compound Name	5-[(Z)-1-cyano-2-(3,4-dihydroxy-5-nitrophenyl)ethenyl]pyrazine-2-carboxylic acid	Investigative
Synonyms	CHEMBL4563060; SCHEMBL21932996 Click to Show/Hide
External link	CID: 140868191
Activity	IC50 <= 300 nM	[140]
Compound Name	2,6-dichloro-4-(3,5-dimethyl-1,2-oxazol-4-yl)-N-[2-(2H-tetrazol-5-yl)phenyl]aniline	Investigative
Synonyms	CHEMBL4532629 Click to Show/Hide
External link	CID: 148272910
Activity	IC50 = 400 nM	[139]
Compound Name	(Z)-3-(3,4-dihydroxy-5-nitrophenyl)-2-pyrimidin-4-ylprop-2-enenitrile	Investigative
Synonyms	CHEMBL4527360; SCHEMBL20100853 Click to Show/Hide
External link	CID: 137283546
Activity	IC50 <= 500 nM	[140]
Compound Name	(Z)-3-amino-2-cyano-3-(3,4-dihydroxy-5-nitrophenyl)-N,N-diethylprop-2-enamide	Investigative
Synonyms	CHEMBL4567049; SCHEMBL20100829 Click to Show/Hide
External link	CID: 134463668
Activity	IC50 <= 500 nM	[140]
Compound Name	(Z)-2-cyano-3-(3,4-dihydroxy-5-nitrophenyl)-3-hydroxy-N-(1,3-thiazol-2-yl)prop-2-enamide	Investigative
Synonyms	CHEMBL4435468; SCHEMBL20100862 Click to Show/Hide
External link	CID: 134463699
Activity	IC50 <= 500 nM	[140]
Compound Name	(Z)-2-cyano-3-(3,4-dihydroxy-5-nitrophenyl)-N,N-diethyl-3-hydroxyprop-2-enamide	Investigative
Synonyms	CHEMBL4461072; SCHEMBL20100822 Click to Show/Hide
External link	CID: 134463661
Activity	IC50 <= 500 nM	[140]
Compound Name	(E)-3-(3,4-dihydroxy-5-nitrophenyl)-3-hydroxy-2-pyrimidin-4-ylprop-2-enenitrile	Investigative
Synonyms	CHEMBL4467308; SCHEMBL20100828 Click to Show/Hide
External link	CID: 137283530
Activity	IC50 <= 500 nM	[140]
Compound Name	(E)-3-(3,4-dihydroxy-5-nitrophenyl)-3-hydroxy-2-pyrazin-2-ylprop-2-enenitrile	Investigative
Synonyms	CHEMBL4529597; SCHEMBL20100823 Click to Show/Hide
External link	CID: 137283525
Activity	IC50 <= 500 nM	[140]
Compound Name	2-[2,6-Dichloro-4-(3,5-dihydroxyphenyl)anilino]benzoic acid	Investigative
Synonyms	CHEMBL4563024 Click to Show/Hide
External link	CID: 153457709
Activity	IC50 = 700 nM	[139]
Compound Name	(Z)-2-(azetidine-1-carbonyl)-3-(3,4-dihydroxy-5-nitrophenyl)-3-hydroxyprop-2-enenitrile	Investigative
Synonyms	CHEMBL4458750; SCHEMBL20100880 Click to Show/Hide
External link	CID: 134463713
Activity	IC50 <= 750 nM	[140]
Compound Name	5-[(E)-1-cyano-2-(3,4-dihydroxy-5-nitrophenyl)-2-hydroxyethenyl]pyrazine-2-carboxylic acid	Investigative
Synonyms	CHEMBL4463923; SCHEMBL21933009 Click to Show/Hide
External link	CID: 140868246
Activity	IC50 <= 750 nM	[140]
Compound Name	(Z)-3-amino-3-(3,4-dihydroxy-5-nitrophenyl)-2-(piperidine-1-carbonyl)prop-2-enenitrile	Investigative
Synonyms	CHEMBL4590326; SCHEMBL20100883 Click to Show/Hide
External link	CID: 134463716
Activity	IC50 <= 750 nM	[140]
Compound Name	(E)-3-(3,4-dihydroxy-5-nitrophenyl)-3-hydroxy-2-pyridin-2-ylprop-2-enenitrile	Investigative
Synonyms	CHEMBL4569935; SCHEMBL20100854 Click to Show/Hide
External link	CID: 137283547
Activity	IC50 <= 750 nM	[140]
Compound Name	Beta-hydroxybutyrate	Investigative
Synonyms	3-hydroxybutanoate; beta-hydroxybutyrate; beta-hydroxybutanoate; 3-OH butyrate; 3-OH-butyrate; beta-hydroxy-n-butyrate; UNII-FG2UN5EP9V; FG2UN5EP9V; DL-3-Hydroxybutyrate; DTXSID9040976; CHEBI:37054; BDBM50270275; Butanoic acid, 3-hydroxy-, ION(1-); Q27117026; 151-03-1 Click to Show/Hide
External link	CID: 3541112 DrugBank: DB03568
Description	FTO fails to bind to its own promoter that promotes FTO expression in the hypothalamus ofhigh-fat diet-induced obese and 48-h fasting mice, suggesting a disruption of the stable expression of this gene.ketogenic diet-derived ketone body beta-hydroxybutyrate (BHB) transiently increases FTO expression in both mouse hypothalamus and cultured cells.	[121]
Compound Name	FB23-2	Investigative
Synonyms	FB23-2; 2243736-45-8; 2-((2,6-Dichloro-4-(3,5-dimethylisoxazol-4-yl)phenyl)amino)-N-hydroxybenzamide; 2-[2,6-dichloro-4-(3,5-dimethyl-1,2-oxazol-4-yl)anilino]-N-hydroxybenzamide; CHEMBL4567838; SCHEMBL23261120; BCP31164; EX-A3403; MFCD32174281; s8837; HY-127103; CS-0093102; FB23-2(FTO Demethylase inhibitor FB23-2); D81008; A936868; FB-23-2; FB 23-2; FB232; FB-232; FB 232; 2-{[2,6-Dichloro-4-(3,5-dimethyl-1,2-oxazol-4-yl)phenyl]amino}-N-hydroxybenzamide Click to Show/Hide
External link	CID: 138454779
Description	FTO is a druggable target and that targeting FTO by small-molecule inhibitors(FB23 and FB23-2) holds potential to treatacute myeloid leukemia.	[104]
Compound Name	DEHP	Investigative
Synonyms	DEHP; 117-81-7; BIS(2-ETHYLHEXYL)PHTHALATE; Di(2-ethylhexyl)phthalate; Di(2-ethylhexyl) phthalate; Diethylhexyl phthalate; 2-Ethylhexyl phthalate; Di-sec-octyl phthalate; Octyl phthalate; Fleximel; Octoil; Ethylhexyl phthalate; Palatinol AH; Celluflex DOP; Vestinol AH; Bisoflex DOP; Kodaflex DOP; Staflex DOP; Truflex DOP; Flexol DOP; Vinicizer 80; Bisoflex 81; Eviplast 80; Eviplast 81; Hercoflex 260; RC plasticizer DOP; Compound 889; Witcizer 312; Platinol dop; Di-2-ethylhexyl phthalate; Nuoplaz dop; Platinol ah; Hatcol dop; Reomol dop; Pittsburgh PX-138; Sansocizer DOP; Ergoplast FDO; Monocizer DOP; Plasthall DOP; Flexol plasticizer DOP; Mollan O; Jayflex DOP; Sicol 150; Ergoplast FDO-S; Di(2-ethylhexyl)orthophthalate; Good-rite gp 264; Reomol D 79P; Bis(2-ethylhexyl) benzene-1,2-dicarboxylate; Di(ethylhexyl) phthalate; Bis(ethylhexyl) phthalate; Rcra waste number U028; Px-138; Phthalic acid dioctyl ester; NCI-C52733; Di(2-ethylhexyl) o-phthalate; Phthalic acid di(2-ethylhexyl) ester; 1,2-Benzenedicarboxylic acid, bis(2-ethylhexyl) ester; DOP; Bis(2-ethylhexyl) 1,2-benzenedicarboxylate; UNII-C42K0PH13C; Bis(2-ethylhexyl) o-phthalate; Phthalic acid, bis(2-ethylhexyl) ester; CHEBI:17747; 1,2-Benzenedicarboxylic acid bis(2-ethylhexyl) ester; Benzenedicarboxylic acid, bis(2-ethylhexyl) ester; Phthalic Acid Bis(2-ethylhexyl) Ester; Bis-(2-ethylhexyl)ester kyseliny ftalove; C42K0PH13C; 1,2-Benzenedicarboxylic acid, 1,2-bis(2-ethylhexyl) ester; DTXSID5020607; Etalon; Bis-(2-ethylhexyl)ester kyseliny ftalove [Czech]; Di-(2-ethylhexyl) phthalate; BIS-(2-ETHYLHEXYL) PHTHALATE; NCGC00091499-05; Sconamoll DOP; Diacizer DOP; Kodaflex DEHP; 15495-94-0; Etalon (plasticizer); Sansocizer R 8000; Caswell No. 392K; Dioctylphthalate; Behp; Di-2-ethylhexylphthalate; Diplast O; ESBO-D 82; Ergoplast FDO; Ergoplast FDO-S; Etalon; Phthalic acid, bis-2-ethylhexyl ester; DOF [Russian plasticizer]; SMR000777878; CCRIS 237; Ethyl hexyl phthalate; HSDB 339; Di(2-ethylhexyl) orthophthalate; Bis-(2-ethylhexyl)ester kyseliny ftalove (czech); EINECS 204-211-0; NSC 17069; Diethylhexylphthalate (Bis-(2-ethylhexyl) Phthalate); RCRA waste no. U028; Union carbide flexol 380; EPA Pesticide Chemical Code 295200; BRN 1890696; AI3-04273; DAF 68; Palatinol DOP; Polycizer DOP; Merrol DOP; Palatinol AH-L; Hatco DOP; Vinycizer 80; Di(2-ethylhexyl)phthalate (DEHP); N-Dioctyl phthalate; MFCD00009493; Corflex 400; Dioctyl phthalate, 99%; DSSTox_CID_607; 1, bis(ethylhexyl) ester; Epitope ID:140107; EC 204-211-0; WLN: 8OVR BVO8; Di(2-Ethylhexyl phthalate); DSSTox_RID_75688; DSSTox_GSID_20607; SCHEMBL20271; 14C -DEHP; 8033-53-2; MLS001333173; MLS001333174; MLS002454397; Dioctyl phthalate, >=99.5%; 1,2-Benzenedicarboxylic acid, bis-(1-ethylhexyl) ester; CHEMBL1242017; SCHEMBL21733281; HMS2233C15; HMS3374J09; AMY40790; HY-B1945; NSC17069; Tox21_400084; Bis(2-ethylhexyl)ester phthalic acid; NSC-17069; s3360; AKOS024318875; Bis(2-ethylhexyl) phthalate-[13C6]; Phthalic acid bis(2-ethylhexyl ester); MCULE-4692716107; NCGC00091499-01; NCGC00091499-02; NCGC00091499-04; NCGC00091499-06; NCGC00091499-07; CAS-117-81-7; I887; Bis(2-ethylhexyl) 1, 2-benzenedicarboxylate; CS-0014050; FT-0624576; FT-0663286; P0297; WLN: 4Y2 & 1OVR BVO1Y4 & 2; Bis(2-ethylhexyl) phthalate, Selectophore(TM); C03690; A937603; Q418492; 1,2-Benzenedicarboxylic acid bis-(1-ethylhexyl) ester; benzene-1,2-dicarboxylic acid bis(2-ethylhexyl) ester; BRD-A89471977-001-05-2; Bis(2-ethylhexyl) phthalate 100 microg/mL in Methanol; Bis(2-ethylhexyl) phthalate 5000 microg/mL in Methanol; F0001-0292; Bis(2-ethylhexyl) phthalate, SAJ first grade, >=98.0%; Bis(2-ethylhexyl) phthalate, PESTANAL(R), analytical standard; Phthalic acid, bis-2-ethylhexyl ester 10 microg/mL in Cyclohexane; Plastic additive 01, European Pharmacopoeia (EP) Reference Standard; Bis(2-ethylhexyl) phthalate, certified reference material, TraceCERT(R); Plastic additive 14, United States Pharmacopeia (USP) Reference Standard; 1,2-Benzenedicarboxylic acid, bis(2-ethylhexyl) ester, labeled with carbon-14; 50885-87-5; 82208-43-3 Click to Show/Hide
External link	CID: 8343
Description	DEHP worsened testicular histology, decreased testosterone concentrations, downregulated expression of spermatogenesis inducers, enhanced oxidative stress, inhibited theNrf2-mediated antioxidant pathway, and increased apoptosis in testes. DEHP is a common environmental endocrine disrupting chemical that inducesmale reproductive disorders. Additionally, DEHP increased global levels of m6A RNA modification and altered the expression of two important RNA methylation modulator genes, FTO and YTHDC2.	[85]
Compound Name	Rhein	Investigative
Synonyms	Monorhein; Rheic acid; Rhubarb Yellow; Cassic acid; 4,5-Dihydroxyanthraquinone-2-carboxylic acid; Chrysazin-3-carboxylic acid; 4,5-dihydroxy-9,10-dioxo-9,10-dihydroanthracene-2-carboxylic acid; NSC 38629; Rheinic acid; 1,8-Dihydroxyanthraquinone-3-carboxylic acid; dipropionyl rhein; 1,8-Dihydroxy-3-carboxyanthraquinone; UNII-YM64C2P6UX; Rhein(Monorhein); 2-Anthracenecarboxylic acid, 9,10-dihydro-4,5-dihydroxy-9,10-dioxo-; CCRIS 5129; 9,10-Dihydro-4,5-dihydroxy-9,10-dioxo-2-anthracenecarboxylic acid; C15H8O6 Click to Show/Hide
External link	CID: 10168 TTD: D0M2TY DrugBank: DB13174
Description	Genetic depletion and pharmacological inhibition of FTO dramatically attenuate leukemia stem/initiating cell self-renewal and reprogram immune response by suppressing expression of immune checkpoint genes, especiallyLILRB4. FTO inhibitors, such as rhein, meclofenamic acid (MA), MO-I-500, fluorescein, and R-2HG, can inhibitacute myeloid leukemia cell viability. CS1 and CS2 displayed a much higher efficacy in inhibiting AML cell viability.	[30]
Compound Name	MO-I-500	Investigative
Description	Genetic depletion and pharmacological inhibition of FTO dramatically attenuate leukemia stem/initiating cell self-renewal and reprogram immune response by suppressing expression of immune checkpoint genes, especiallyLILRB4. FTO inhibitors, such as rhein, meclofenamic acid (MA), MO-I-500, fluorescein, and R-2HG, can inhibitacute myeloid leukemia cell viability. CS1 and CS2 displayed a much higher efficacy in inhibiting AML cell viability.	[30]
Compound Name	R-2HG	Investigative
Synonyms	(R)-2-Hydroxypentanedioic acid; 13095-47-1; D-2-Hydroxyglutaric acid; (R)-2-hydroxyglutaric acid; (R)-Hydroxyglutarate; (R)-2-hydroxyglutarate; Pentanedioic acid, 2-hydroxy-, (2R)-; CHEMBL1614745; CHEBI:32796; D-2-Hydroxyglutarate; Glutaric acid, 2-hydroxy-; d-alpha-hydroxyglutaric acid; D-Hydroxyglutarate; 2HG; D-a-Hydroxyglutarate; 2-hydroxy-D-Glutarate; (R)-a-Hydroxyglutarate; delta-2-Hydroxyglutarate; D-a-Hydroxyglutaric acid; 2-hydroxy-delta-Glutarate; D-; A-Hydroxyglutaric acid; (2R)-hydroxyglutaric acid; 2-hydroxy-D-Glutaric acid; (R)-alpha-Hydroxyglutarate; delta-alpha-Hydroxyglutarate; SCHEMBL8032; (R)-a-Hydroxyglutaric acid; delta-2-Hydroxyglutaric acid; (R)-2-hydroxy-Pentanedioate; 2-hydroxy-delta-Glutaric acid; (R)-alpha-Hydroxyglutaric acid; delta-alpha-Hydroxyglutaric acid; (R)-2-hydroxy-Pentanedioic acid; DTXSID80897218; ZINC402968; BDBM50361471; AKOS027325193; FD21404; BS-50252; HY-113038; CS-0059411; C01087; 93397C3E-3CE9-4FEA-A2ED-8F6FA59A1FEA; Q27104222; Z2217110365; 636-67-9 Click to Show/Hide
External link	CID: 439391
Description	Genetic depletion and pharmacological inhibition of FTO dramatically attenuate leukemia stem/initiating cell self-renewal and reprogram immune response by suppressing expression of immune checkpoint genes, especiallyLILRB4. FTO inhibitors, such as rhein, meclofenamic acid (MA), MO-I-500, fluorescein, and R-2HG, can inhibitacute myeloid leukemia cell viability. CS1 and CS2 displayed a much higher efficacy in inhibiting AML cell viability.	[30]
Compound Name	Mehp	Investigative
Synonyms	Mehp; Mono(2-ethylhexyl) phthalate; PHTHALIC ACID MONO-2-ETHYLHEXYL ESTER; Mono(2-ethylhexyl)phthalate; 2-Ethylhexyl hydrogen phthalate; Monoethylhexyl phthalate; MONO-2-ETHYLHEXYL PHTHALATE; Mono-(2-ethylhexyl)phthalate; 2-(2-ethylhexoxycarbonyl)benzoic acid; (2-Ethylhexyl) hydrogen phthalate; 1,2-Benzenedicarboxylic acid, mono(2-ethylhexyl) ester; 2-{[(2-ethylhexyl)oxy]carbonyl}benzoic acid; Monoethylhexyl phthalic acid; Phthalic acid, mono-(2-ethylhexyl) ester; CHEBI:17243; PHTHALIC ACID MONOOCTYL ESTER; Phthalic acid mono-2-ethylhexylester; Phthalic acid, mono-2-ethylhexyl ester; NCGC00090773-04; 1276197-22-8; BAR 1; Phthalate, mono(2-ethylhexyl); CCRIS 1742; 2-([(2-Ethylhexyl)oxy]carbonyl)benzoic acid; rac Mono(ethylhexyl) Phthalate-d4; EINECS 224-477-1; mono(ethylhexyl) phthalate; mono-ethylhexyl; Mono-(2-ethylhexyl) phthalate; rac Mono(ethylhexyl) Phthalate; monoethylhexylphthalate; mono-ethylhexylphthalate; DSSTox_CID_5680; Phthalic acid, 2-ethylhexyl ester (6CI,7CI); DSSTox_RID_77879; DSSTox_GSID_25680; phthalicacidmonoethylhexylester; phthalicacid,2-ethylhexylester; SCHEMBL472689; mono-(2-ethyl)hexyl phthalate; PHTHALICACIDMONOETHYLHEXYL; CHEMBL1867438; DTXSID2025680; Monoethylhexyl phthalate (mEHP); phthalic acid, 2-ethylhexyl ester; Mono-(2-ethylhexyl) phthalate-d4; ACT03365; Tox21_400076; MFCD00041500; AKOS015902975; CS-W019178; HY-W018392; 2-(2-ethylhexyloxycarbonyl)benzoic acid; PHTHALICACIDMONO-2-ETHYLEXYLESTER; NCGC00090773-01; NCGC00090773-02; NCGC00090773-03; NCGC00090773-05; NCGC00090773-06; DS-16446; CAS-4376-20-9; DB-007821; 2-[(2S)-2-ethylhexoxy]carbonylbenzoic acid; FT-0600523; Phthalic acid mono-2-ethylhexyl ester liquid; Phthalic acid mono-2-ethylhexyl ester, 97%; W6291; C03343; Phthalic acid hydrogen 1-(2-ethylhexyl) ester; 2-([(2-Ethylhexyl)oxy]carbonyl)benzoic acid #; A826416; Phthalic acid 1-hydrogen 2-(2-ethylhexyl) ester; phthalic acid mono-2-ethylhexyl ester, AldrichCPR; 1,2-benzenedicarboxylicacid,mono(2-ethylhexyl)ester; BRD-A18246003-001-01-1; Q26841225; 1,2-Benzenedicarboxylic acid, mono(2-ethylhexyl) ester (9CI); Phthalic acid, mono-2-ethylhexyl ester 100 microg/mL in Acetonitrile Click to Show/Hide
External link	CID: 20393
Description	The inhibition of FTO-mediated up-regulation of m6A could be involved in MEHP-inducedLeydig cell apoptosis.	[137]
Compound Name	Cycloleucine	Investigative
Synonyms	1-Aminocyclopentanecarboxylic acid; 52-52-8; 1-Aminocyclopentane-1-carboxylic acid; Cycloleucin; 1-Amino-1-cyclopentanecarboxylic acid; 1-Amino-1-carboxycyclopentane; 1-Amino-cyclopentanecarboxylic acid; CYCLO-LEUCINE; Cyclopentanecarboxylic acid, 1-amino-; NSC 1026; CB 1639; X 201; UNII-0TQU7668EI; 1-Aminocyclopentanecarboxylate; HSDB 5195; WR 14,997; NSC1026; 1-amino cyclopentane carboxylic acid; EINECS 200-144-6; BRN 0636626; aminocyclopentanecarboxylic acid; Cyclopentanecarboxylic acid, 1-amino-, L-; AI3-26442 Click to Show/Hide
External link	CID: 2901 TTD: D0P0GT DrugBank: DB04620
Description	Studies of the aberrant expression of m6A mediators inbreast cancer revealed that they were associated with different BC subtypes and functions, such as proliferation, apoptosis, stemness, the cell cycle, migration, and metastasis, through several factors and signaling pathways, such asBcl-2 and the PI3K/Akt pathway, among others. Fat mass and obesity-associated protein (FTO) was identified as the first m6A demethylase, and a series of inhibitors that target FTO were reported to have potential for the treatment of BC by inhibiting cell proliferation and promoting apoptosis.	[4]
Compound Name	4-amino-3-quinolinecarboxylic acid	Investigative
Synonyms	4-amino-3-quinolinecarboxylic acid; 4-Amino-quinoline-3-carboxylic acid; 3-Quinolinecarboxylicacid, 4-amino-; 4-aminoquinoline-3-carboxylic; SCHEMBL436714; DTXSID10470018; BBL031107; MFCD08705653; STK660776; ZINC14982158; AKOS002326679; MCULE-8408161492; SB67440; VS-10248; DB-081679; BB 0222277; CS-0248109; FT-0748901; Y9812; EN300-39148; J-514466; F2183-0223; Z398556732 Click to Show/Hide
External link	CID: 11651286
Description	Inhibition of m6A RNA demethylation by small-molecule drugs, as presented here, has therapeutic potential and provides tools for the identification of disease-modifying m6A RNAs inneurogenesis and neuroregeneration. Small-molecule inhibitors of the RNA m6A demethylases FTO potently support the survival of dopamine neurons.	[123]

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Ref 53	Autophagy of the m(6)A mRNA demethylase FTO is impaired by low-level arsenic exposure to promote tumorigenesis. Nat Commun. 2021 Apr 12;12(1):2183. doi: 10.1038/s41467-021-22469-6.
Ref 54	M(6) A demethylase fat mass and obesity-associated protein regulates cisplatin resistance of gastric cancer by modulating autophagy activation through ULK1. Cancer Sci. 2022 Jun 22. doi: 10.1111/cas.15469. Online ahead of print.
Ref 55	FTO promotes Bortezomib resistance via m6A-dependent destabilization of SOD2 expression in multiple myeloma. Cancer Gene Ther. 2022 Feb 10. doi: 10.1038/s41417-022-00429-6. Online ahead of print.
Ref 56	m(6)A RNA demethylase FTO promotes the growth, migration and invasion of pancreatic cancer cells through inhibiting TFPI-2. Epigenetics. 2022 Apr 11:1-15. doi: 10.1080/15592294.2022.2061117. Online ahead of print.
Ref 57	SPI1-induced?downregulation of FTO promotes GBM progression by regulating pri-miR-10a processing in an m6A-dependent manner. Mol Ther Nucleic Acids. 2022 Jan 1;27:699-717. doi: 10.1016/j.omtn.2021.12.035. eCollection 2022 Mar 8.
Ref 58	FTO demethylates YAP mRNA promoting oral squamous cell carcinoma tumorigenesis. Neoplasma. 2022 Jan;69(1):71-79. doi: 10.4149/neo_2021_210716N967. Epub 2021 Nov 16.
Ref 59	m(6)A demethylase FTO regulates the apoptosis and inflammation of cardiomyocytes via YAP1 in ischemia-reperfusion injury. Bioengineered. 2022 Mar;13(3):5443-5452. doi: 10.1080/21655979.2022.2030572.
Ref 60	Downregulation of Fat Mass and Obesity Associated (FTO) Promotes the Progression of Intrahepatic Cholangiocarcinoma. Front Oncol. 2019 May 9;9:369. doi: 10.3389/fonc.2019.00369. eCollection 2019.
Ref 61	M(6)A methylation-mediated elevation of SM22Alpha?inhibits the proliferation and migration of?vascular smooth muscle cells and ameliorates?intimal hyperplasia in type 2 diabetes mellitus. Biol Chem. 2021 Dec 7;403(3):317-329. doi: 10.1515/hsz-2021-0296. Print 2022 Feb 23.
Ref 62	CircRAB11FIP1 promoted autophagy flux of ovarian cancer through DSC1 and miR-129. Cell Death Dis. 2021 Feb 26;12(2):219. doi: 10.1038/s41419-021-03486-1.
Ref 63	m(6)A mRNA methylation controls autophagy and adipogenesis by targeting Atg5 and Atg7. Autophagy. 2020 Jul;16(7):1221-1235. doi: 10.1080/15548627.2019.1659617. Epub 2019 Aug 26.
Ref 64	FTO modifies the m6A level of MALAT and promotes bladder cancer progression. Clin Transl Med. 2021 Feb;11(2):e310. doi: 10.1002/ctm2.310.
Ref 65	Changes and relationship of N(6)-methyladenosine modification and long non-coding RNAs in oxidative damage induced by cadmium in pancreatic Beta-cells. Toxicol Lett. 2021 Jun 1;343:56-66. doi: 10.1016/j.toxlet.2021.02.014. Epub 2021 Feb 24.
Ref 66	The RNA N6-Methyladenosine Demethylase FTO Promotes Head and Neck Squamous Cell Carcinoma Proliferation and Migration by Increasing CTNNB1. Int J Gen Med. 2021 Nov 24;14:8785-8795. doi: 10.2147/IJGM.S339095. eCollection 2021.
Ref 67	FTO regulates the chemo-radiotherapy resistance of cervical squamous cell carcinoma (CSCC) by targeting Beta-catenin through mRNA demethylation. Mol Carcinog. 2018 May;57(5):590-597. doi: 10.1002/mc.22782. Epub 2018 Feb 1.
Ref 68	Meclofenamic acid promotes cisplatin-induced acute kidney injury by inhibiting fat mass and obesity-associated protein-mediated m(6)A abrogation in RNA. J Biol Chem. 2019 Nov 8;294(45):16908-16917. doi: 10.1074/jbc.RA119.011009. Epub 2019 Oct 2.
Ref 69	N6-methyladenosine demethylase FTO suppressed prostate cancer progression by maintaining CLIC4 mRNA stability. Cell Death Discov. 2022 Apr 9;8(1):184. doi: 10.1038/s41420-022-01003-7.
Ref 70	FTO promotes tumour proliferation in bladder cancer via the FTO/miR-576/CDK6 axis in an m6A-dependent manner. Cell Death Discov. 2021 Nov 1;7(1):329. doi: 10.1038/s41420-021-00724-5.
Ref 71	Methylation of adenosine at the N(6) position post-transcriptionally regulates hepatic P450s expression. Biochem Pharmacol. 2020 Jan;171:113697. doi: 10.1016/j.bcp.2019.113697. Epub 2019 Nov 7.
Ref 72	RNA m(6)A methylation regulates the ultraviolet-induced DNA damage response. Nature. 2017 Mar 23;543(7646):573-576. doi: 10.1038/nature21671. Epub 2017 Mar 15.
Ref 73	m6A demethylase FTO promotes tumor progression via regulation of lipid metabolism in esophageal cancer. Cell Biosci. 2022 May 14;12(1):60. doi: 10.1186/s13578-022-00798-3.
Ref 74	N6-methyladenosine demethyltransferase FTO-mediated autophagy in malignant development of oral squamous cell carcinoma. Oncogene. 2021 Jun;40(22):3885-3898. doi: 10.1038/s41388-021-01820-7. Epub 2021 May 10.
Ref 75	Fat mass and obesity-associated protein regulates lipogenesis via m(6) A modification in fatty acid synthase mRNA. Cell Biol Int. 2021 Feb;45(2):334-344. doi: 10.1002/cbin.11490. Epub 2020 Nov 8.
Ref 76	N6-methyladenosine Demethylase FTO Induces the Dysfunctions of Ovarian Granulosa Cells by Upregulating Flotillin 2. Reprod Sci. 2022 Apr;29(4):1305-1315. doi: 10.1007/s43032-021-00664-6. Epub 2021 Jul 12.
Ref 77	FTO promotes colorectal cancer progression and chemotherapy resistance via demethylating G6PD/PARP1. Clin Transl Med. 2022 Mar;12(3):e772. doi: 10.1002/ctm2.772.
Ref 78	N(6)-Methyladenosine Demethylase FTO Contributes to Neuropathic Pain by Stabilizing G9a Expression in Primary Sensory Neurons. Adv Sci (Weinh). 2020 May 27;7(13):1902402. doi: 10.1002/advs.201902402. eCollection 2020 Jul.
Ref 79	HOXB13 promotes gastric cancer cell migration and invasion via IGF-1R upregulation and subsequent activation of PI3K/AKT/mTOR signaling pathway. Life Sci. 2021 Aug 1;278:119522. doi: 10.1016/j.lfs.2021.119522. Epub 2021 Apr 21.
Ref 80	FTO demethylates m6A modifications in HOXB13 mRNA and promotes endometrial cancer metastasis by activating the WNT signalling pathway. RNA Biol. 2021 Sep;18(9):1265-1278. doi: 10.1080/15476286.2020.1841458. Epub 2020 Nov 5.
Ref 81	miRNA-mediated loss of m6A increases nascent translation in glioblastoma. PLoS Genet. 2021 Mar 8;17(3):e1009086. doi: 10.1371/journal.pgen.1009086. eCollection 2021 Mar.
Ref 82	IDH Mutation, Competitive Inhibition of FTO, and RNA Methylation. Cancer Cell. 2017 May 8;31(5):619-620. doi: 10.1016/j.ccell.2017.04.001.
Ref 83	FTO regulates ocular angiogenesis via m(6)A-YTHDF2-dependent mechanism. Exp Eye Res. 2020 Aug;197:108107. doi: 10.1016/j.exer.2020.108107. Epub 2020 Jun 9.
Ref 84	FTO downregulation mediated by hypoxia facilitates colorectal cancer metastasis. Oncogene. 2021 Aug;40(33):5168-5181. doi: 10.1038/s41388-021-01916-0. Epub 2021 Jul 3.
Ref 85	Increased m6A RNA modification is related to the inhibition of the Nrf2-mediated antioxidant response in di-(2-ethylhexyl) phthalate-induced prepubertal testicular injury. Environ Pollut. 2020 Apr;259:113911. doi: 10.1016/j.envpol.2020.113911. Epub 2020 Jan 6.
Ref 86	FTO-dependent demethylation of N6-methyladenosine regulates mRNA splicing and is required for adipogenesis. Cell Res. 2014 Dec;24(12):1403-19. doi: 10.1038/cr.2014.151. Epub 2014 Nov 21.
Ref 87	m6A demethylase FTO induces NELL2 expression by inhibiting E2F1 m6A modification leading to metastasis of non-small cell lung cancer. Mol Ther Oncolytics. 2021 Apr 29;21:367-376. doi: 10.1016/j.omto.2021.04.011. eCollection 2021 Jun 25.
Ref 88	FTO mediated ERBB2 demethylation promotes tumor progression in esophageal squamous cell carcinoma cells. Clin Exp Metastasis. 2022 Aug;39(4):623-639. doi: 10.1007/s10585-022-10169-4. Epub 2022 May 7.
Ref 89	Fat mass and obesity-associated protein (FTO) mediates signal transducer and activator of transcription 3 (STAT3)-drived resistance of breast cancer to doxorubicin. Bioengineered. 2021 Dec;12(1):1874-1889. doi: 10.1080/21655979.2021.1924544.
Ref 90	FTO-mediated m(6) A modification of SOCS1 mRNA promotes the progression of diabetic kidney disease. Clin Transl Med. 2022 Jun;12(6):e942. doi: 10.1002/ctm2.942.
Ref 91	The m6A demethylase FTO promotes the growth of lung cancer cells by regulating the m6A level of USP7 mRNA. Biochem Biophys Res Commun. 2019 May 7;512(3):479-485. doi: 10.1016/j.bbrc.2019.03.093. Epub 2019 Mar 21.
Ref 92	FTO-stabilized lncRNA HOXC13-AS epigenetically upregulated FZD6 and activated Wnt/Beta-catenin signaling to drive cervical cancer proliferation, invasion, and EMT. J BUON. 2021 Jul-Aug;26(4):1279-1291.
Ref 93	FTO overexpression inhibits apoptosis of hypoxia/reoxygenation-treated myocardial cells by regulating m6A modification of Mhrt. Mol Cell Biochem. 2021 May;476(5):2171-2179. doi: 10.1007/s11010-021-04069-6. Epub 2021 Feb 6.
Ref 94	FTO Inhibition Enhances the Antitumor Effect of Temozolomide by Targeting MYC-miR-155/23a Cluster-MXI1 Feedback Circuit in Glioma. Cancer Res. 2020 Sep 15;80(18):3945-3958. doi: 10.1158/0008-5472.CAN-20-0132. Epub 2020 Jul 17.
Ref 95	SMAD3 and FTO are involved in miR-5581-3p-mediated inhibition of cell migration and proliferation in bladder cancer. Cell Death Discov. 2022 Apr 13;8(1):199. doi: 10.1038/s41420-022-01010-8.
Ref 96	m(6)A-mediated upregulation of AC008 promotes osteoarthritis progression through the miR-328-3p?AQP1/ANKH axis. Exp Mol Med. 2021 Nov;53(11):1723-1734. doi: 10.1038/s12276-021-00696-7. Epub 2021 Nov 4.
Ref 97	N(6)-methyladenosine mediates the cellular proliferation and apoptosis via microRNAs in arsenite-transformed cells. Toxicol Lett. 2018 Aug;292:1-11. doi: 10.1016/j.toxlet.2018.04.018. Epub 2018 Apr 20.
Ref 98	N(6) -Methyladenosine Negatively Regulates Human Respiratory Syncytial Virus Replication. Front Cell Dev Biol. 2021 Oct 4;9:739445. doi: 10.3389/fcell.2021.739445. eCollection 2021.
Ref 99	The Potential Role of N6-Methyladenosine (m6A) Demethylase Fat Mass and Obesity-Associated Gene (FTO) in Human Cancers. Onco Targets Ther. 2020 Dec 15;13:12845-12856. doi: 10.2147/OTT.S283417. eCollection 2020.
Ref 100	Roles of N6-Methyladenosine Demethylase FTO in Malignant Tumors Progression. Onco Targets Ther. 2021 Sep 16;14:4837-4846. doi: 10.2147/OTT.S329232. eCollection 2021.
Ref 101	Downregulation of the FTO m(6)A RNA demethylase promotes EMT-mediated progression of epithelial tumors and sensitivity to Wnt inhibitors. Nat Cancer. 2021 Jun;2(6):611-628. doi: 10.1038/s43018-021-00223-7. Epub 2021 Jun 23.
Ref 102	Saikosaponin D exhibits anti-leukemic activity by targeting FTO/m(6)A signaling. Theranostics. 2021 Mar 31;11(12):5831-5846. doi: 10.7150/thno.55574. eCollection 2021.
Ref 103	The Yin and Yang of RNA Methylation: An Imbalance of Erasers Enhances Sensitivity to FTO Demethylase Small-Molecule Targeting in Leukemia Stem Cells. Cancer Cell. 2019 Apr 15;35(4):540-541. doi: 10.1016/j.ccell.2019.03.011.
Ref 104	Small-Molecule Targeting of Oncogenic FTO Demethylase in Acute Myeloid Leukemia. Cancer Cell. 2019 Apr 15;35(4):677-691.e10. doi: 10.1016/j.ccell.2019.03.006.
Ref 105	A dynamic N(6)-methyladenosine methylome regulates intrinsic and acquired resistance to tyrosine kinase inhibitors. Cell Res. 2018 Nov;28(11):1062-1076. doi: 10.1038/s41422-018-0097-4. Epub 2018 Oct 8.
Ref 106	Integrated analysis of transcriptome-wide m(6)A methylome of osteosarcoma stem cells enriched by chemotherapy. Epigenomics. 2019 Nov 1;11(15):1693-1715. doi: 10.2217/epi-2019-0262. Epub 2019 Oct 25.
Ref 107	Expression of Demethylase Genes, FTO and ALKBH1, Is Associated with Prognosis of Gastric Cancer. Dig Dis Sci. 2019 Jun;64(6):1503-1513. doi: 10.1007/s10620-018-5452-2. Epub 2019 Jan 14.
Ref 108	Gene Polymorphisms of m6A Erasers FTO and ALKBH1 Associated with Susceptibility to Gastric Cancer. Pharmgenomics Pers Med. 2022 May 31;15:547-559. doi: 10.2147/PGPM.S360912. eCollection 2022.
Ref 109	To Develop and Validate the Combination of RNA Methylation Regulators for the Prognosis of Patients with Gastric Cancer. Onco Targets Ther. 2020 Oct 23;13:10785-10795. doi: 10.2147/OTT.S276239. eCollection 2020.
Ref 110	Berberine Suppresses Stemness and Tumorigenicity of Colorectal Cancer Stem-Like Cells by Inhibiting m(6)A Methylation. Front Oncol. 2021 Nov 15;11:775418. doi: 10.3389/fonc.2021.775418. eCollection 2021.
Ref 111	SIRT1 Regulates N(6) -Methyladenosine RNA Modification in Hepatocarcinogenesis by Inducing RANBP2-Dependent FTO SUMOylation. Hepatology. 2020 Dec;72(6):2029-2050. doi: 10.1002/hep.31222. Epub 2020 Oct 22.
Ref 112	Fat mass and obesity-associated protein promotes the tumorigenesis and development of liver cancer. Oncol Lett. 2020 Aug;20(2):1409-1417. doi: 10.3892/ol.2020.11673. Epub 2020 May 25.
Ref 113	FTO Facilitates Lung Adenocarcinoma Cell Progression by Activating Cell Migration Through mRNA Demethylation. Onco Targets Ther. 2020 Feb 18;13:1461-1470. doi: 10.2147/OTT.S231914. eCollection 2020.
Ref 114	FTO-Dependent N (6)-Methyladenosine Modifications Inhibit Ovarian Cancer Stem Cell Self-Renewal by Blocking cAMP Signaling. Cancer Res. 2020 Aug 15;80(16):3200-3214. doi: 10.1158/0008-5472.CAN-19-4044. Epub 2020 Jun 30.
Ref 115	RNA m6A Methylation Regulators Multi-Omics Analysis in Prostate Cancer. Front Genet. 2021 Nov 26;12:768041. doi: 10.3389/fgene.2021.768041. eCollection 2021.
Ref 116	The FTO m(6)A demethylase inhibits the invasion and migration of prostate cancer cells by regulating total m(6)A levels. Life Sci. 2021 Apr 15;271:119180. doi: 10.1016/j.lfs.2021.119180. Epub 2021 Feb 8.
Ref 117	The N(6) -methyladenosine (m(6) A) erasers alkylation repair homologue 5 (ALKBH5) and fat mass and obesity-associated protein (FTO) are prognostic biomarkers in patients with clear cell renal carcinoma. BJU Int. 2020 Apr;125(4):617-624. doi: 10.1111/bju.15019. Epub 2020 Feb 17.
Ref 118	MiR-155 regulates m(6)A level and cell progression by targeting FTO in clear cell renal cell carcinoma. Cell Signal. 2022 Mar;91:110217. doi: 10.1016/j.cellsig.2021.110217. Epub 2021 Dec 16.
Ref 119	Interplay between RNA Methylation Eraser FTO and Writer METTL3 in Renal Clear Cell Carcinoma Patient Survival. Recent Pat Anticancer Drug Discov. 2021;16(3):363-376. doi: 10.2174/1574892816666210204125155.
Ref 120	Decreased N(6)-methyladenosine in peripheral blood RNA from diabetic patients is associated with FTO expression rather than ALKBH5. J Clin Endocrinol Metab. 2015 Jan;100(1):E148-54. doi: 10.1210/jc.2014-1893.
Ref 121	FTO is a transcriptional repressor to auto-regulate its own gene and potentially associated with homeostasis of body weight. J Mol Cell Biol. 2019 Feb 1;11(2):118-132. doi: 10.1093/jmcb/mjy028.
Ref 122	AMPK regulates lipid accumulation in skeletal muscle cells through FTO-dependent demethylation of N(6)-methyladenosine. Sci Rep. 2017 Feb 8;7:41606. doi: 10.1038/srep41606.
Ref 123	Small-Molecule Inhibitors of the RNA M6A Demethylases FTO Potently Support the Survival of Dopamine Neurons. Int J Mol Sci. 2021 Apr 26;22(9):4537. doi: 10.3390/ijms22094537.
Ref 124	Abnormality of m6A mRNA Methylation Is Involved in Alzheimer's Disease. Front Neurosci. 2020 Feb 28;14:98. doi: 10.3389/fnins.2020.00098. eCollection 2020.
Ref 125	Streptozotocin-Induced Astrocyte Mitochondrial Dysfunction Is Ameliorated by FTO Inhibitor MO-I-500. ACS Chem Neurosci. 2021 Oct 20;12(20):3818-3828. doi: 10.1021/acschemneuro.1c00063. Epub 2021 Sep 7.
Ref 126	m6A Demethylase FTO Regulates Dopaminergic Neurotransmission Deficits Caused by Arsenite. Toxicol Sci. 2018 Oct 1;165(2):431-446. doi: 10.1093/toxsci/kfy172.
Ref 127	Meclofenamic Acid Reduces Reactive Oxygen Species Accumulation and Apoptosis, Inhibits Excessive Autophagy, and Protects Hair Cell-Like HEI-OC1 Cells From Cisplatin-Induced Damage. Front Cell Neurosci. 2018 May 23;12:139. doi: 10.3389/fncel.2018.00139. eCollection 2018.
Ref 128	Changes in N6-Methyladenosine Modification Modulate Diabetic Cardiomyopathy by Reducing Myocardial Fibrosis and Myocyte Hypertrophy. Front Cell Dev Biol. 2021 Jul 21;9:702579. doi: 10.3389/fcell.2021.702579. eCollection 2021.
Ref 129	FTO-Dependent N(6)-Methyladenosine Regulates Cardiac Function During Remodeling and Repair. Circulation. 2019 Jan 22;139(4):518-532. doi: 10.1161/CIRCULATIONAHA.118.033794.
Ref 130	Increased m6A methylation level is associated with the progression of human abdominal aortic aneurysm. Ann Transl Med. 2019 Dec;7(24):797. doi: 10.21037/atm.2019.12.65.
Ref 131	Alteration of N(6)-Methyladenosine mRNA Methylation in a Human Stem Cell-Derived Cardiomyocyte Model of Tyrosine Kinase Inhibitor-Induced Cardiotoxicity. Front Cardiovasc Med. 2022 Mar 23;9:849175. doi: 10.3389/fcvm.2022.849175. eCollection 2022.
Ref 132	FTO-dependent function of N6-methyladenosine is involved in the hepatoprotective effects of betaine on adolescent mice. J Physiol Biochem. 2015 Sep;71(3):405-13. doi: 10.1007/s13105-015-0420-1. Epub 2015 Jun 16.
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Ref 134	Increased N6-methyladenosine causes infertility is associated with FTO expression. J Cell Physiol. 2018 Sep;233(9):7055-7066. doi: 10.1002/jcp.26507. Epub 2018 Mar 25.
Ref 135	Cyclophosphamide Regulates N6-Methyladenosine and m6A RNA Enzyme Levels in Human Granulosa Cells and in Ovaries of a Premature Ovarian Aging Mouse Model. Front Endocrinol (Lausanne). 2019 Jun 27;10:415. doi: 10.3389/fendo.2019.00415. eCollection 2019.
Ref 136	Regulation of autophagy in leukocytes through RNA N(6)-adenosine methylation in chronic kidney disease patients. Biochem Biophys Res Commun. 2020 Jul 5;527(4):953-959. doi: 10.1016/j.bbrc.2020.04.138. Epub 2020 May 18.
Ref 137	Increased m6A modification of RNA methylation related to the inhibition of demethylase FTO contributes to MEHP-induced Leydig cell injury. Environ Pollut. 2021 Jan 1;268(Pt A):115627. doi: 10.1016/j.envpol.2020.115627. Epub 2020 Sep 24.
Ref 138	m(6)A RNA modification controls autophagy through upregulating ULK1 protein abundance. Cell Res. 2018 Sep;28(9):955-957. doi: 10.1038/s41422-018-0069-8. Epub 2018 Jul 25.
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m6A Regulator Information

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Prof. Feng ZHU

Prof. Shuiping Liu

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