m6A Regulator Information

General Information of the m6A Regulator (ID: REG00006)

Regulator Name	Methyltransferase-like 14 (METTL14)
Synonyms	N6-adenosine-methyltransferase non-catalytic subunit; hMETTL14; KIAA1627 Click to Show/Hide
Gene Name	METTL14
Sequence	MDSRLQEIRERQKLRRQLLAQQLGAESADSIGAVLNSKDEQREIAETRETCRASYDTSAP NAKRKYLDEGETDEDKMEEYKDELEMQQDEENLPYEEEIYKDSSTFLKGTQSLNPHNDYC QHFVDTGHRPQNFIRDVGLADRFEEYPKLRELIRLKDELIAKSNTPPMYLQADIEAFDIR ELTPKFDVILLEPPLEEYYRETGITANEKCWTWDDIMKLEIDEIAAPRSFIFLWCGSGEG LDLGRVCLRKWGYRRCEDICWIKTNKNNPGKTKTLDPKAVFQRTKEHCLMGIKGTVKRST DGDFIHANVDIDLIITEEPEIGNIEKPVEIFHIIEHFCLGRRRLHLFGRDSTIRPGWLTV GPTLTNSNYNAETYASYFSAPNSYLTGCTEEIERLRPKSPPPKSKSDRGGGAPRGGGRGG TSAGRGRERNRSNFRGERGGFRGGRGGAHRGGFPPR Click to Show/Hide
Family	MT-A70-like family
Function	The METTL3-METTL14 heterodimer forms a N6-methyltransferase complex that methylates adenosine residues at the N(6) position of some mRNAs and regulates the circadian clock, differentiation of embryonic stem cells and cortical neurogenesis. In the heterodimer formed with METTL3, METTL14 constitutes the RNA-binding scaffold that recognizes the substrate rather than the catalytic core. N6-methyladenosine (m6A), which takes place at the 5'-[AG]GAC-3' consensus sites of some mRNAs, plays a role in mRNA stability and processing. M6A acts as a key regulator of mRNA stability by promoting mRNA destabilization and degradation (By similarity). In embryonic stem cells (ESCs), m6A methylation of mRNAs encoding key naive pluripotency-promoting transcripts results in transcript destabilization (By similarity). M6A regulates spermatogonial differentiation and meiosis and is essential for male fertility and spermatogenesis (By similarity). M6A also regulates cortical neurogenesis: m6A methylation of transcripts related to transcription factors, neural stem cells, the cell cycle and neuronal differentiation during brain development promotes their destabilization and decay, promoting differentiation of radial glial cells (By similarity). Click to Show/Hide
Gene ID	57721
Uniprot ID	MET14_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)

METTL14 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

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Apoptosis regulator Bcl-2 (BCL2)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL14*
Cell Line	MDA-MB-231	Homo sapiens
Treatment: siMETTL14 MDA-MB-231 cells Control: MDA-MB-231 cells		GSE81164
Regulation		logFC: 6.46E-01 p-value: 1.74E-05
More Results	Click to View More RNA-seq Results

Atherosclerosis [ICD-11: BD40]

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	Atherosclerosis [ICD-11: BD40.Z]
Target Regulation	Down regulation
Pathway Response	Apoptosis			hsa04210
Cell Process	Cell apoptosis
In-vitro Model	HUVEC-C	Normal	Homo sapiens	CVCL_2959
In-vitro Model	EA.hy 926	Normal	Homo sapiens	CVCL_3901
In-vivo Model	The mice were randomly divided into control, Ad-sh-NC, and Ad-sh-METTL14 groups (10 mice per group). The mice in the control group were fed a normal diet, while the Ad-sh-NC and Ad-sh-METTL14 groups were fed a high-fat diet (20% fat and 0.25% cholesterol). Furthermore, 300 uL of constructed sh-NC or sh-METTL14 adenovirus was injected every 3 weeks into the caudal veins of mice from the Ad-sh-NC or Ad-sh-METTL14 groups, respectively. The constructed vectors were obtained from HanBio Technology Co., Ltd. (Shanghai, China). All mice were sacrificed after 24 weeks and the aortas were separated for further experiments.
Response Summary	Knocking down METTL14 could inhibit the development of atherosclerosis in high-fat diet-treated APOE mice. After transfection with si-METTL14, the Apoptosis regulator Bcl-2 (BCL2) expression level and the viability of ox-LDL-incubated cells increased, whereas the apoptosis rate and the expressions of Bax and cleaved caspase-3 decreased. However, the effect of METTL14 knockdown was reversed by p65 overexpression.

Arrestin domain-containing protein 4 (ARRDC4)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL14*
Cell Line	MDA-MB-231	Homo sapiens
Treatment: siMETTL14 MDA-MB-231 cells Control: MDA-MB-231 cells		GSE81164
Regulation		logFC: -1.00E+00 p-value: 7.16E-13
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				[2]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulation	Up regulation
Pathway Response	mRNA surveillance pathway			hsa03015), RNA degradation
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
	NCM460	Normal	Homo sapiens	CVCL_0460
	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
In-vivo Model	Equal amount of HCT116 cells (2 × 10⁶) stably expression of relevant plasmids was injected into the right flank of mice, tumor bulks was monitored once a week after injection and volumes were counted as 0.5 × a2 × b (a and b respectively indicated short and long diameter of tumor).
Response Summary	Knockdown of METTL14 significantly enhanced Arrestin domain-containing protein 4 (ARRDC4) mRNA stability relying on the "reader" protein YHTDF2 dependent manner in colorectal cancer.

ATP-citrate synthase (ACLY)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL14*
Cell Line	MDA-MB-231	Homo sapiens
Treatment: siMETTL14 MDA-MB-231 cells Control: MDA-MB-231 cells		GSE81164
Regulation		logFC: 7.95E-01 p-value: 2.66E-12
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				[3]
Responsed Disease	Non-alcoholic fatty liver disease [ICD-11: DB92]
Target Regulation	Up regulation
Pathway Response	Glycerolipid metabolism			hsa00561
Cell Process	Lipid metabolism
In-vitro Model	LM3	Malignant neoplasms	Mus musculus	CVCL_D269
In-vitro Model	MHCC97-H	Adult hepatocellular carcinoma	Homo sapiens	CVCL_4972
In-vivo Model	Mice with a Tmem30a deletion specifically in pancreatic beta cells were generated as previously described. Mice developed with NAFLD were named for Tmem30a-associated NAFLD (TAN) mice. The littermate mice with genotypes of Tmem30a^loxP/loxP were used as controls.
Response Summary	Targeting METTL3/14 in vitro increases protein level of ATP-citrate synthase (ACLY) and SCD1 as well as triglyceride and cholesterol production and accumulation of lipid droplets. These findings demonstrate a new NAFLD mouse model that provides a study platform for DM2-related NAFLD and reveals a unique epitranscriptional regulating mechanism for lipid metabolism via m6A-modified protein expression of ACLY and SCD1.

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

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL14*
Cell Line	BMDM	Mus musculus
Treatment: METTL14 knockout mice BMDM Control: Wild type mice BMDM		GSE153512
Regulation		logFC: 7.03E-01 p-value: 9.23E-10
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]
Target Regulation	Up regulation
Cell Process	Cell apoptosis
Response Summary	LNC942-METTL14-C-X-C chemokine receptor type 4 (CXCR4)/CYP1B1 signaling axis, which provides new targets and crosstalk m6A epigenetic modification mechanism for breast cancer prevention and treatment.

Inflammatory response [ICD-11: MG46]

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	Inflammatory response [ICD-11: MG46]
Target Regulation	Up regulation
In-vitro Model	HUVEC-C	Normal	Homo sapiens	CVCL_2959

C-X-C motif chemokine 10 (Cxcl10)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL14*
Cell Line	CT26 cell line	Mus musculus
Treatment: METTL14 knockout CT26 cells Control: CT26 cells		GSE142589
Regulation		logFC: 1.83E+00 p-value: 1.84E-06
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				[5]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulation	Down regulation
Pathway Response	PD-L1 expression and PD-1 checkpoint pathway in cancer			hsa05235
Cell Process	Immunity
In-vitro Model	CT26	Mouse colon adenocarcinoma	Mus musculus	CVCL_7254
	B16-GM-CSF (B16-GM-CSF cell line was a kind gift from Drs. Glenn Dranoff and Michael Dougan (Dana-Farber/Harvard Cancer Center))
	B16-F10	Mouse melanoma	Mus musculus	CVCL_0159
In-vivo Model	2 × 10⁶ CT26 cells with knockout of Mettl3, Mettl14, Mettl3/Stat1, Mettl3/Irf1, Mettl14/Stat1, or Mettl14/Irf1 and control were suspended in 200 uL of PBS/Matrigel (Corning) (1:1) and then subcutaneously inoculated into flank of each mouse.
Response Summary	In colorectal cancer, Mettl3- or Mettl14-deficient tumors increased cytotoxic tumor-infiltrating CD8+ T cells and elevated secretion of IFN-gamma, Cxcl9, and C-X-C motif chemokine 10 (Cxcl10) in tumor microenvironment in vivo. Mechanistically, Mettl3 or Mettl14 loss promoted IFN-gamma-Stat1-Irf1 signaling through stabilizing the Stat1 and Irf1 mRNA via Ythdf2.

C-X-C motif chemokine 9 (Cxcl9)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL14*
Cell Line	CT26 cell line	Mus musculus
Treatment: METTL14 knockout CT26 cells Control: CT26 cells		GSE142589
Regulation		logFC: 2.27E+00 p-value: 1.06E-06
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				[5]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulation	Down regulation
Pathway Response	PD-L1 expression and PD-1 checkpoint pathway in cancer			hsa05235
Cell Process	Immunity
In-vitro Model	CT26	Mouse colon adenocarcinoma	Mus musculus	CVCL_7254
	B16-GM-CSF (B16-GM-CSF cell line was a kind gift from Drs. Glenn Dranoff and Michael Dougan (Dana-Farber/Harvard Cancer Center))
	B16-F10	Mouse melanoma	Mus musculus	CVCL_0159
In-vivo Model	2 × 10⁶ CT26 cells with knockout of Mettl3, Mettl14, Mettl3/Stat1, Mettl3/Irf1, Mettl14/Stat1, or Mettl14/Irf1 and control were suspended in 200 uL of PBS/Matrigel (Corning) (1:1) and then subcutaneously inoculated into flank of each mouse.
Response Summary	In colorectal cancer, Mettl3- or Mettl14-deficient tumors increased cytotoxic tumor-infiltrating CD8+ T cells and elevated secretion of IFN-gamma, C-X-C motif chemokine 9 (Cxcl9), and Cxcl10 in tumor microenvironment in vivo. Mechanistically, Mettl3 or Mettl14 loss promoted IFN-gamma-Stat1-Irf1 signaling through stabilizing the Stat1 and Irf1 mRNA via Ythdf2.

Calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK2)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL14*
Cell Line	Neural progenitor cell line	Mus musculus
Treatment: METTL14 knockout NPCs Control: Wild type NPCs		GSE158985
Regulation		logFC: 5.88E-01 p-value: 3.22E-03
More Results	Click to View More RNA-seq Results

Male infertility [ICD-11: GB04]

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	Azoospermia [ICD-11: GB04.0]
Target Regulation	Down regulation
Pathway Response	Autophagy			hsa04140
Cell Process	RNA stability
	Cell autophagy
In-vitro Model	TM3	Normal	Mus musculus	CVCL_4326
In-vivo Model	Male SPF BALB/c mice (qls02-0202) were purchased from Qinglongshan animal breeding farm. Mice were sacrificed by CO₂ asphyxiation and testes were obtained for following histopathological analyses.
Response Summary	m6A modification promoted translation of PPM1A (protein phosphatase 1A, magnesium dependent, alpha isoform), a negative AMP-activated protein kinase (AMPK) regulator, but decreased expression of Calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK2) (calcium/calmodulin-dependent protein kinase kinase 2, beta), a positive AMPK regulator, by reducing its RNA stability. Similar regulation of METTL14, ALKBH5, and m6A was also observed in LCs upon treatment with human chorionic gonadotropin (HsCG). Knock down of YTHDF1 failed to change the expression of CAMKK2 Providing insight into novel therapeutic strategies by exploiting m6A RNA methylation as targets for treating azoospermatism and oligospermatism patients with reduction in serum testosterone.

Caspase-3 (CASP3)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL14*
Cell Line	Embryonic stem cells	Mus musculus
Treatment: METTL14 knockout mESCs Control: Wild type mESCs		GSE156481
Regulation		logFC: -6.38E-01 p-value: 2.86E-05
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				[7]
Responsed Disease	Osteosarcoma [ICD-11: 2B51]
Target Regulation	Up regulation
Pathway Response	Apoptosis			hsa04210
Cell Process	Cell proliferation
	Cell migration
	Cell invasion
	Cell apoptosis
In-vitro Model	143B	Osteosarcoma	Homo sapiens	CVCL_2270
	U2OS	Osteosarcoma	Homo sapiens	CVCL_0042
Response Summary	METTL14 can promote osteosarcoma cell apoptosis, inhibit cell viability, and have a tumor suppressor effect on osteosarcoma. METTL14 finally achieves apoptosis by activating Caspase-3 (CASP3).

Catenin beta-1 (CTNNB1/Beta-catenin)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL14*
Cell Line	BMDM	Mus musculus
Treatment: METTL14 knockout mice BMDM Control: Wild type mice BMDM		GSE153512
Regulation		logFC: -6.10E-01 p-value: 2.52E-16
More Results	Click to View More RNA-seq Results

Breast cancer [ICD-11: 2C60]

In total 3 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[8]
Responsed Disease	Breast cancer [ICD-11: 2C60]
Responsed Drug	Pertuzumab		Approved	Drug Info
Target Regulation	Down regulation
Pathway Response	Wnt signaling pathway			hsa04310
Cell Process	Glutathione synthesis
In-vitro Model	ZR-75-1	Invasive breast carcinoma	Homo sapiens	CVCL_0588
	T-47D	Invasive breast carcinoma	Homo sapiens	CVCL_0553
	SUM-159 (A mesenchymal triple-negative breast cancer cell line)
	SK-BR-3	Breast adenocarcinoma	Homo sapiens	CVCL_0033
	MDA-MB-468	Breast adenocarcinoma	Homo sapiens	CVCL_0419
	MDA-MB-453	Breast adenocarcinoma	Homo sapiens	CVCL_0418
	MDA-MB-361	Breast adenocarcinoma	Homo sapiens	CVCL_0620
	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
	HEK293T	Normal	Homo sapiens	CVCL_0063
	BT-549	Invasive breast carcinoma	Homo sapiens	CVCL_1092
	BT-474	Invasive breast carcinoma	Homo sapiens	CVCL_0179
	AU565	Breast adenocarcinoma	Homo sapiens	CVCL_1074
In-vivo Model	Luciferase-labeled rSKBR3 and MDA-MB-361 cells (1 × 10⁷ cells) mixed with 1:1 Matrigel (Corning, 356237) were subcutaneously injected into the fat pads of mice. After a tumor was palpable, the mice were randomized into four groups (five mice per group), and they were treated with vehicle, trastuzumab (20 mg/kg, intraperitoneal administration), roblitinib (30 mg/kg, oral administration), or a combination of both drugs.
Response Summary	m6A-hypomethylation regulated FGFR4 phosphorylates GSK-3beta and activates Catenin beta-1 (CTNNB1/Beta-catenin)/TCF4-SLC7A11/FPN1 signaling to drive anti-HER2 resistance. Knockdown of METTL14 significantly increased the expression level of FGFR4 in HER2-positive breast cancer cells. FGFR4 reduced the sensitivity of HER2-positive breast cancer to trastuzumab plus pertuzumab or tucatinib. These results pinpoint a mechanism of anti-HER2 resistance and provide a strategy for overcoming resistance via FGFR4 inhibition in recalcitrant HER2-positive breast cancer.
Experiment 2 Reporting the m6A-centered Disease Response of This Target Gene				[8]
Responsed Disease	Breast cancer [ICD-11: 2C60]
Responsed Drug	Trastuzumab		Approved	Drug Info
Target Regulation	Down regulation
Pathway Response	Wnt signaling pathway			hsa04310
Cell Process	Glutathione synthesis
In-vitro Model	ZR-75-1	Invasive breast carcinoma	Homo sapiens	CVCL_0588
	T-47D	Invasive breast carcinoma	Homo sapiens	CVCL_0553
	SUM-159 (A mesenchymal triple-negative breast cancer cell line)
	SK-BR-3	Breast adenocarcinoma	Homo sapiens	CVCL_0033
	MDA-MB-468	Breast adenocarcinoma	Homo sapiens	CVCL_0419
	MDA-MB-453	Breast adenocarcinoma	Homo sapiens	CVCL_0418
	MDA-MB-361	Breast adenocarcinoma	Homo sapiens	CVCL_0620
	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
	HEK293T	Normal	Homo sapiens	CVCL_0063
	BT-549	Invasive breast carcinoma	Homo sapiens	CVCL_1092
	BT-474	Invasive breast carcinoma	Homo sapiens	CVCL_0179
	AU565	Breast adenocarcinoma	Homo sapiens	CVCL_1074
In-vivo Model	Luciferase-labeled rSKBR3 and MDA-MB-361 cells (1 × 10⁷ cells) mixed with 1:1 Matrigel (Corning, 356237) were subcutaneously injected into the fat pads of mice. After a tumor was palpable, the mice were randomized into four groups (five mice per group), and they were treated with vehicle, trastuzumab (20 mg/kg, intraperitoneal administration), roblitinib (30 mg/kg, oral administration), or a combination of both drugs.
Response Summary	m6A-hypomethylation regulated FGFR4 phosphorylates GSK-3beta and activates Catenin beta-1 (CTNNB1/Beta-catenin)/TCF4-SLC7A11/FPN1 signaling to drive anti-HER2 resistance. Knockdown of METTL14 significantly increased the expression level of FGFR4 in HER2-positive breast cancer cells. FGFR4 reduced the sensitivity of HER2-positive breast cancer to trastuzumab plus pertuzumab or tucatinib. These results pinpoint a mechanism of anti-HER2 resistance and provide a strategy for overcoming resistance via FGFR4 inhibition in recalcitrant HER2-positive breast cancer.
Experiment 3 Reporting the m6A-centered Disease Response of This Target Gene				[8]
Responsed Disease	Breast cancer [ICD-11: 2C60]
Responsed Drug	Tucatinib		Approved	Drug Info
Target Regulation	Down regulation
Pathway Response	Wnt signaling pathway			hsa04310
Cell Process	Glutathione synthesis
In-vitro Model	ZR-75-1	Invasive breast carcinoma	Homo sapiens	CVCL_0588
	T-47D	Invasive breast carcinoma	Homo sapiens	CVCL_0553
	SUM-159 (A mesenchymal triple-negative breast cancer cell line)
	SK-BR-3	Breast adenocarcinoma	Homo sapiens	CVCL_0033
	MDA-MB-468	Breast adenocarcinoma	Homo sapiens	CVCL_0419
	MDA-MB-453	Breast adenocarcinoma	Homo sapiens	CVCL_0418
	MDA-MB-361	Breast adenocarcinoma	Homo sapiens	CVCL_0620
	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
	HEK293T	Normal	Homo sapiens	CVCL_0063
	BT-549	Invasive breast carcinoma	Homo sapiens	CVCL_1092
	BT-474	Invasive breast carcinoma	Homo sapiens	CVCL_0179
	AU565	Breast adenocarcinoma	Homo sapiens	CVCL_1074
In-vivo Model	Luciferase-labeled rSKBR3 and MDA-MB-361 cells (1 × 10⁷ cells) mixed with 1:1 Matrigel (Corning, 356237) were subcutaneously injected into the fat pads of mice. After a tumor was palpable, the mice were randomized into four groups (five mice per group), and they were treated with vehicle, trastuzumab (20 mg/kg, intraperitoneal administration), roblitinib (30 mg/kg, oral administration), or a combination of both drugs.
Response Summary	m6A-hypomethylation regulated FGFR4 phosphorylates GSK-3beta and activates Catenin beta-1 (CTNNB1/Beta-catenin)/TCF4-SLC7A11/FPN1 signaling to drive anti-HER2 resistance. Knockdown of METTL14 significantly increased the expression level of FGFR4 in HER2-positive breast cancer cells. FGFR4 reduced the sensitivity of HER2-positive breast cancer to trastuzumab plus pertuzumab or tucatinib. These results pinpoint a mechanism of anti-HER2 resistance and provide a strategy for overcoming resistance via FGFR4 inhibition in recalcitrant HER2-positive breast cancer.

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		[9]
Responsed Disease	Ischemic heart disease [ICD-11: BA40-BA6Z]
Target Regulation	Up regulation
Pathway Response	Wnt signaling pathway	hsa04310
In-vitro Model	Neonatal rat ventricular cardiomyocytes (Primary myocyte cells)
In-vivo Model	C57BL/6 mouse hearts were subjected to ischemia/reperfusion (I/R) in vivo as described previously (Bock-Marquette et al., 2004; Song et al., 2015; Brocard et al., 2017). I/R injury in mice was induced by 45-min ischemia, followed by 7-day and 4-week reperfusion in a loss-of-function study (Figure 1) and gain-of-function study (Figure 2), respectively. In brief, mice were anesthetized with 2% avertin (0.1 ml/10g body weight; Sigma-Aldrich Corporation, United States) through intraperitoneal injection. To generate I/R injury, the left anterior descending coronary artery (LAD) was ligated with 7-0 nylon for 45 min and then was removed. For the sham group, a suture was passed under the LAD but without ligation. According to the experimental requirements, at different time points of cardiac I/R, the mice were anesthetized for assessing heart function by echocardiographic measurement. All the mice survived during the process of I/R injury after the operation.
Response Summary	Mettl14 resulted in enhanced levels of Wnt1 m6A modification and Wnt1 protein but not its transcript level.Furthermore, Mettl14 overexpression blocked I/R-induced downregulation of Wnt1 and Catenin beta-1 (CTNNB1/Beta-catenin) proteins, whereas Mettl14 hearts exhibited the opposite results. Mettl14 attenuates cardiac I/R injury by activating Wnt/Bete-catenin in an m6A-dependent manner, providing a novel therapeutic target for ischemic heart disease.

Cyclin-dependent kinase inhibitor 1 (CDKN1A)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL14*
Cell Line	Neural progenitor cell line	Mus musculus
Treatment: METTL14 knockout NPCs Control: Wild type NPCs		GSE158985
Regulation		logFC: -9.21E-01 p-value: 1.04E-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				[10]
Responsed Disease	Acute myeloid leukaemia [ICD-11: 2A60]
Target Regulation	Up regulation
Pathway Response	p53 signaling pathway			hsa04115
Pathway Response	Cell cycle			hsa04110
Cell Process	Cell apoptosis
Cell Process	Cells in G7/M phase decreased
In-vitro Model	THP-1	Childhood acute monocytic leukemia	Homo sapiens	CVCL_0006
	NB4	Acute promyelocytic leukemia	Homo sapiens	CVCL_0005
	MV4-11	Childhood acute monocytic leukemia	Homo sapiens	CVCL_0064
	MOLT-4	Adult T acute lymphoblastic leukemia	Homo sapiens	CVCL_0013
	Kasumi-1	Myeloid leukemia with maturation	Homo sapiens	CVCL_0589
	K-562	Chronic myelogenous leukemia	Homo sapiens	CVCL_0004
	HL-60	Adult acute myeloid leukemia	Homo sapiens	CVCL_0002
	HEL	Erythroleukemia	Homo sapiens	CVCL_0001
	CCRF-CEM C7	T acute lymphoblastic leukemia	Homo sapiens	CVCL_6825
	HEK293T	Normal	Homo sapiens	CVCL_0063
Response Summary	METTL3 and METTL14 play an oncogenic role in acute myeloid leukemia(AML) by targeting mdm2/p53 signal pathway. The knockdown of METTL3 and METTL14 in K562 cell line leads to several changes in the expression of p53 signal pathway, including the upregulation of p53, cyclin dependent kinase inhibitor 1A (CDKN1A/Cyclin-dependent kinase inhibitor 1 (CDKN1A)), and downregulation of mdm2.

Ageing-related disease [ICD-11: 9B10-9B60]

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	Ageing-related disease [ICD-11: 9B10-9B60]
Target Regulation	Up regulation
In-vitro Model	HCT 116 TP53(-/-)	Colon carcinoma	Homo sapiens	CVCL_HD97
In-vitro Model	HeLa	Endocervical adenocarcinoma	Homo sapiens	CVCL_0030

Cystine/glutamate transporter (SLC7A11)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL14*
Cell Line	HepG2 cell line	Homo sapiens
Treatment: shMETTL14 HepG2 cells Control: shCtrl HepG2 cells		GSE121949
Regulation		logFC: -1.11E+00 p-value: 3.96E-11
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				[11]
Responsed Disease	Liver cancer [ICD-11: 2C12]
Target Regulation	Down regulation
Pathway Response	HIF-1 signaling pathway			hsa04066
Cell Process	RNA stability
In-vitro Model	PLC/PRF/5	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0485
	MHCC97-H	Adult hepatocellular carcinoma	Homo sapiens	CVCL_4972
	L-02	Endocervical adenocarcinoma	Homo sapiens	CVCL_6926
	Huh-7	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0336
	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
	HCCLM3	Adult hepatocellular carcinoma	Homo sapiens	CVCL_6832
	BEL-7402	Endocervical adenocarcinoma	Homo sapiens	CVCL_5492
	7721 (Human hepatic malignant cell line)
In-vivo Model	For the subcutaneous implantation model, 5 × 10⁵ stable SLC7A11-knockdown HCCLM3 cells or SLC7A11-vector cells were injected subcutaneously into BALB/C nude mice.
Response Summary	METTL14 induced m6A modification at 5'UTR of Cystine/glutamate transporter (SLC7A11) mRNA, which in turn underwent degradation relied on the YTHDF2-dependent pathway. Identify the HIF-1alpha /METTL14/YTHDF2/SLC7A11 axis as a potential therapeutic target for the HCC interventional embolization treatment.

Breast cancer [ICD-11: 2C60]

In total 3 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[8]
Responsed Disease	Breast cancer [ICD-11: 2C60]
Responsed Drug	Pertuzumab		Approved	Drug Info
Target Regulation	Down regulation
Pathway Response	Wnt signaling pathway			hsa04310
Cell Process	Glutathione synthesis
In-vitro Model	ZR-75-1	Invasive breast carcinoma	Homo sapiens	CVCL_0588
	T-47D	Invasive breast carcinoma	Homo sapiens	CVCL_0553
	SUM-159 (A mesenchymal triple-negative breast cancer cell line)
	SK-BR-3	Breast adenocarcinoma	Homo sapiens	CVCL_0033
	MDA-MB-468	Breast adenocarcinoma	Homo sapiens	CVCL_0419
	MDA-MB-453	Breast adenocarcinoma	Homo sapiens	CVCL_0418
	MDA-MB-361	Breast adenocarcinoma	Homo sapiens	CVCL_0620
	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
	HEK293T	Normal	Homo sapiens	CVCL_0063
	BT-549	Invasive breast carcinoma	Homo sapiens	CVCL_1092
	BT-474	Invasive breast carcinoma	Homo sapiens	CVCL_0179
	AU565	Breast adenocarcinoma	Homo sapiens	CVCL_1074
In-vivo Model	Luciferase-labeled rSKBR3 and MDA-MB-361 cells (1 × 10⁷ cells) mixed with 1:1 Matrigel (Corning, 356237) were subcutaneously injected into the fat pads of mice. After a tumor was palpable, the mice were randomized into four groups (five mice per group), and they were treated with vehicle, trastuzumab (20 mg/kg, intraperitoneal administration), roblitinib (30 mg/kg, oral administration), or a combination of both drugs.
Response Summary	m6A-hypomethylation regulated FGFR4 phosphorylates GSK-3beta and activates beta-catenin/TCF4-Cystine/glutamate transporter (SLC7A11)/FPN1 signaling to drive anti-HER2 resistance. Knockdown of METTL14 significantly increased the expression level of FGFR4 in HER2-positive breast cancer cells. FGFR4 reduced the sensitivity of HER2-positive breast cancer to trastuzumab plus pertuzumab or tucatinib. These results pinpoint a mechanism of anti-HER2 resistance and provide a strategy for overcoming resistance via FGFR4 inhibition in recalcitrant HER2-positive breast cancer.
Experiment 2 Reporting the m6A-centered Disease Response of This Target Gene				[8]
Responsed Disease	Breast cancer [ICD-11: 2C60]
Responsed Drug	Trastuzumab		Approved	Drug Info
Target Regulation	Down regulation
Pathway Response	Wnt signaling pathway			hsa04310
Cell Process	Glutathione synthesis
In-vitro Model	ZR-75-1	Invasive breast carcinoma	Homo sapiens	CVCL_0588
	T-47D	Invasive breast carcinoma	Homo sapiens	CVCL_0553
	SUM-159 (A mesenchymal triple-negative breast cancer cell line)
	SK-BR-3	Breast adenocarcinoma	Homo sapiens	CVCL_0033
	MDA-MB-468	Breast adenocarcinoma	Homo sapiens	CVCL_0419
	MDA-MB-453	Breast adenocarcinoma	Homo sapiens	CVCL_0418
	MDA-MB-361	Breast adenocarcinoma	Homo sapiens	CVCL_0620
	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
	HEK293T	Normal	Homo sapiens	CVCL_0063
	BT-549	Invasive breast carcinoma	Homo sapiens	CVCL_1092
	BT-474	Invasive breast carcinoma	Homo sapiens	CVCL_0179
	AU565	Breast adenocarcinoma	Homo sapiens	CVCL_1074
In-vivo Model	Luciferase-labeled rSKBR3 and MDA-MB-361 cells (1 × 10⁷ cells) mixed with 1:1 Matrigel (Corning, 356237) were subcutaneously injected into the fat pads of mice. After a tumor was palpable, the mice were randomized into four groups (five mice per group), and they were treated with vehicle, trastuzumab (20 mg/kg, intraperitoneal administration), roblitinib (30 mg/kg, oral administration), or a combination of both drugs.
Response Summary	m6A-hypomethylation regulated FGFR4 phosphorylates GSK-3beta and activates beta-catenin/TCF4-Cystine/glutamate transporter (SLC7A11)/FPN1 signaling to drive anti-HER2 resistance. Knockdown of METTL14 significantly increased the expression level of FGFR4 in HER2-positive breast cancer cells. FGFR4 reduced the sensitivity of HER2-positive breast cancer to trastuzumab plus pertuzumab or tucatinib. These results pinpoint a mechanism of anti-HER2 resistance and provide a strategy for overcoming resistance via FGFR4 inhibition in recalcitrant HER2-positive breast cancer.
Experiment 3 Reporting the m6A-centered Disease Response of This Target Gene				[8]
Responsed Disease	Breast cancer [ICD-11: 2C60]
Responsed Drug	Tucatinib		Approved	Drug Info
Target Regulation	Down regulation
Pathway Response	Wnt signaling pathway			hsa04310
Cell Process	Glutathione synthesis
In-vitro Model	ZR-75-1	Invasive breast carcinoma	Homo sapiens	CVCL_0588
	T-47D	Invasive breast carcinoma	Homo sapiens	CVCL_0553
	SUM-159 (A mesenchymal triple-negative breast cancer cell line)
	SK-BR-3	Breast adenocarcinoma	Homo sapiens	CVCL_0033
	MDA-MB-468	Breast adenocarcinoma	Homo sapiens	CVCL_0419
	MDA-MB-453	Breast adenocarcinoma	Homo sapiens	CVCL_0418
	MDA-MB-361	Breast adenocarcinoma	Homo sapiens	CVCL_0620
	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
	HEK293T	Normal	Homo sapiens	CVCL_0063
	BT-549	Invasive breast carcinoma	Homo sapiens	CVCL_1092
	BT-474	Invasive breast carcinoma	Homo sapiens	CVCL_0179
	AU565	Breast adenocarcinoma	Homo sapiens	CVCL_1074
In-vivo Model	Luciferase-labeled rSKBR3 and MDA-MB-361 cells (1 × 10⁷ cells) mixed with 1:1 Matrigel (Corning, 356237) were subcutaneously injected into the fat pads of mice. After a tumor was palpable, the mice were randomized into four groups (five mice per group), and they were treated with vehicle, trastuzumab (20 mg/kg, intraperitoneal administration), roblitinib (30 mg/kg, oral administration), or a combination of both drugs.
Response Summary	m6A-hypomethylation regulated FGFR4 phosphorylates GSK-3beta and activates beta-catenin/TCF4-Cystine/glutamate transporter (SLC7A11)/FPN1 signaling to drive anti-HER2 resistance. Knockdown of METTL14 significantly increased the expression level of FGFR4 in HER2-positive breast cancer cells. FGFR4 reduced the sensitivity of HER2-positive breast cancer to trastuzumab plus pertuzumab or tucatinib. These results pinpoint a mechanism of anti-HER2 resistance and provide a strategy for overcoming resistance via FGFR4 inhibition in recalcitrant HER2-positive breast cancer.

Cytochrome P450 1B1 (CYP1B1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL14*
Cell Line	MDA-MB-231	Homo sapiens
Treatment: siMETTL14 MDA-MB-231 cells Control: MDA-MB-231 cells		GSE81164
Regulation		logFC: -1.14E+00 p-value: 9.74E-11
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]
Target Regulation	Up regulation
Cell Process	Cell apoptosis
Response Summary	LNC942-METTL14-CXCR4/Cytochrome P450 1B1 (CYP1B1) signaling axis, which provides new targets and crosstalk m6A epigenetic modification mechanism for breast cancer prevention and treatment.

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				[66]
Responsed Disease	Cervical cancer [ICD-11: 2C77]
Target Regulation	Down regulation
In-vitro Model	Ca Ski	Cervical squamous cell carcinoma	Homo sapiens	CVCL_1100
	SiHa	Cervical squamous cell carcinoma	Homo sapiens	CVCL_0032
	End1/E6E7	Normal	Homo sapiens	CVCL_3684
In-vivo Model	To examine the effects of piRNA-14633 on subcutaneous xenograft growth, BALB/c nude mice (Beijing Vital River Laboratory Animal Technology) were subcutaneously injected with 0.1 mL of cell suspension containing 2 × 10⁶ cells. Tumor volume (mm3) was measured every 4 days using a Vernier caliper and calculated as 0.4 x (short length)2 × long length.

Dexamethasone-induced Ras-related protein 1 (RASD1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL14*
Cell Line	mouse embryonic stem cells	Mus musculus
Treatment: METTL14-/- ESCs Control: Wild type ESCs		GSE145309
Regulation		logFC: -1.81E+00 p-value: 2.87E-02
More Results	Click to View More RNA-seq Results

Injuries of spine or trunk [ICD-11: ND51]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[12]
Responsed Disease	Injuries of spine or trunk [ICD-11: ND51]
Target Regulation	Down regulation
Pathway Response	mTOR signaling pathway			hsa04150
In-vitro Model	C8-D1A	Normal	Mus musculus	CVCL_6379
In-vitro Model	C8-B4	Normal	Mus musculus	CVCL_6378
In-vivo Model	An incision was made in the skin along the medial dorsal line to the aponeurotic and muscular planes, and the posterior vertebral arches were exposed from T8 to T12. Under the dissection stereomicroscope, 3-mm-long laminectomy was performed on the caudal end of T10 vertebra and the rostral end of T11 vertebra. The Infinite Horizons impactor (Infinite Horizons, L.L.C., Lexington, KY, USA) was adopted to produce the contusion SCI using a force of 60 kdyn/cm². The SCI model rats were established and randomly assigned to SCI model group, ant-NC (negative control, SCI rats treated with lentiviral (lv)-shRNA NC of Mettl14) group and ant-Mettl14 group (SCI rats treated with lv-shRNA of Mettl14). Rats were subjected to laminectomy and then treated with lv-shRNA Mettl14/lv-shRNA-NC (50 ul/day, 100 nmoL/mL; RiboBio, Guangzhou, China) via an intrathecal injection through lumbar puncture for 3 days (0, 1, and 2 days) after 15 min of SCI modelling. In addition, the unmodeled rats were set as sham group.
Response Summary	Mettl14-mediated m6A modification inhibited Dexamethasone-induced Ras-related protein 1 (RASD1) and induced the apoptosis of spinal cord neurons in SCI by promoting the transformation of pri-miR-375 to mature miR-375.

DNA damage-binding protein 2 (DDB2)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL14*
Cell Line	MDA-MB-231	Homo sapiens
Treatment: siMETTL14 MDA-MB-231 cells Control: MDA-MB-231 cells		GSE81164
Regulation		logFC: -7.35E-01 p-value: 7.54E-04
More Results	Click to View More RNA-seq Results

Skin tumour [ICD-11: 2F92]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[13]
Responsed Disease	Skin tumour [ICD-11: 2F92]
Target Regulation	Up regulation
Pathway Response	Nucleotide excision repair			hsa03420
Cell Process	Genome repair
	Cell autophagy
In-vitro Model	NHEK (Normal human epithelial keratinocytes)
	MEF (Mouse embryonic fibroblasts)
	HaCaT	Normal	Homo sapiens	CVCL_0038
	A-431	Skin squamous cell carcinoma	Homo sapiens	CVCL_0037
Response Summary	METTL14 knockdown decreases GGR and DNA damage-binding protein 2 (DDB2) abundance. Conversely, overexpression of wild-type METTL14 but not its enzymatically inactive mutant increases GGR and DDB2 abundance. METTL14 is a target for selective autophagy and acts as a critical epitranscriptomic mechanism to regulate GGR and suppress UVB-induced skin tumorigenesis.

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

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL14*
Cell Line	mouse embryonic stem cells	Mus musculus
Treatment: METTL14-/- ESCs Control: Wild type ESCs		GSE145309
Regulation		logFC: -2.08E+00 p-value: 8.68E-26
More Results	Click to View More RNA-seq Results

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				[14]
Responsed Disease	Liver disease [ICD-11: DB9Z]
Target Regulation	Down regulation
Pathway Response	Ubiquitin mediated proteolysis			hsa04120
Cell Process	Cell apoptosis
	Ubiquitination degradation
In-vitro Model	HEK293	Normal	Homo sapiens	CVCL_0045
	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
Response Summary	METTL14 promotes DNA damage-inducible transcript 3 protein (DDIT3/CHOP) mRNA decay through its 3' UTR N6-methyladenosine (m6A) to inhibit its downstream pro-apoptotic target gene expression, suppress ER proteotoxic liver disease. UPR induces METTL14 expression by competing against the HRD1-ER-associated degradation (ERAD) machinery to block METTL14 ubiquitination and degradation.

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				[68]
Responsed Disease	Liver hepatocellular carcinoma [ICD-11: 2C12.02]
Responsed Drug	Regorafenib		Approved	Drug Info
In-vitro Model	Huh-7	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0336
	SK-HEP-1	Liver and intrahepatic bile duct epithelial neoplasm	Homo sapiens	CVCL_0525
	HCCLM3	Adult hepatocellular carcinoma	Homo sapiens	CVCL_6832
	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
In-vivo Model	After one week of acclimatization, the nude mice were randomly divided into 5 groups (n = 3): Control, vehicle + oe-NC, vehicle + oe-CHOP, Regorafenib + oe-NC, and Regorafenib + oe-CHOP. The Control group was injected with untreated SK-Hep-1 cells. The vehicle + oe-NC group and Regorafenib + oe-NC group were injected with SK-Hep-1 cells transfected with oe-NC. vehicle + oe-CHOP group and Regorafenib + oe-CHOP group were injected with SK-Hep-1 cells transfected with oe-CHOP.

E3 ubiquitin-protein ligase TRIM7 (TRIM7)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL14*
Cell Line	mouse embryonic stem cells	Mus musculus
Treatment: METTL14-/- ESCs Control: Wild type ESCs		GSE145309
Regulation		logFC: -1.06E+00 p-value: 1.08E-12
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				[15]
Responsed Disease	Osteosarcoma [ICD-11: 2B51]
Target Regulation	Down regulation
Pathway Response	Ubiquitin mediated proteolysis			hsa04120
Cell Process	Proteasome pathway degradation
In-vitro Model	U2OS	Osteosarcoma	Homo sapiens	CVCL_0042
	SaOS-2	Osteosarcoma	Homo sapiens	CVCL_0548
	MG-63	Osteosarcoma	Homo sapiens	CVCL_0426
	HOS	Osteosarcoma	Homo sapiens	CVCL_0312
	hFOB 1.19	Normal	Homo sapiens	CVCL_3708
In-vivo Model	MG63 cells transduced with lentivirus expressing shTRIM7 or shNC, and SAOS2 cells transduced with lentivirus expressing TRIM7, BRMS1, TRIM7 plus BRMS1 or control vector, were injected via the tail vein into the nude mice (1 × 10⁶ cells/mouse) (n = 11 per group).
Response Summary	E3 ubiquitin-protein ligase TRIM7 (TRIM7) mRNA stability was regulated by the METTL3/14-YTHDF2-mRNA in a decay-dependent manner. TRIM7 plays a key role in regulating metastasis and chemoresistance in osteosarcoma through ubiquitination of BRMS1.

ELAV-like protein 1 (HuR/ELAVL1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL14*
Cell Line	Neural progenitor cell line	Mus musculus
Treatment: METTL14 knockout NPCs Control: Wild type NPCs		GSE158985
Regulation		logFC: 8.91E-01 p-value: 1.25E-03
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				[16]
Responsed Disease	Solid tumour/cancer [ICD-11: 2A00-2F9Z]
Target Regulation	Up regulation
Cell Process	RNA stability
Cell Process	Cell apoptosis
In-vitro Model	BT-549	Invasive breast carcinoma	Homo sapiens	CVCL_1092
	DU145	Prostate carcinoma	Homo sapiens	CVCL_0105
	HeLa	Endocervical adenocarcinoma	Homo sapiens	CVCL_0030
	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
	MDA-MB-231	Breast adenocarcinoma	Homo sapiens	CVCL_0062
	MDA-MB-468	Breast adenocarcinoma	Homo sapiens	CVCL_0419
In-vivo Model	For tumor xenograft studies, MDA-MB-231 cells transfected with scrambled-siRNA or METTL14-siRNA or ALKBH5-siRNA (2 × 10⁶) were mixed with Matrigel and injected subcutaneously in the flank of 6-week-old female athymic nude mice.
Response Summary	METTL14 and ALKBH5 determine the m6A status of target genes by controlling each other's expression and by inhibiting m6A reader YTHDF3 (YTH N 6-methyladenosine RNA binding protein 3), which blocks RNA demethylase activity. ALKBH5/METTL14 constitute a positive feedback loop with RNA stability factor ELAV-like protein 1 (HuR/ELAVL1) to regulate the stability of target transcripts. This study unveils a previously undefined role for m6A in cancer and shows that the collaboration among writers-erasers-readers sets up the m6A threshold to ensure the stability of progrowth/proliferation-specific genes, and protumorigenic stimulus.

Elongation factor 1-alpha 2 (EEF1A2)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL14*
Cell Line	HepG2 cell line	Homo sapiens
Treatment: shMETTL14 HepG2 cells Control: shCtrl HepG2 cells		GSE121949
Regulation		logFC: -2.52E+00 p-value: 5.01E-13
More Results	Click to View More RNA-seq Results

Injuries of spine or trunk [ICD-11: ND51]

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	Injuries of spine or trunk [ICD-11: ND51]
Target Regulation	Down regulation
Pathway Response	PI3K-Akt signaling pathway			hsa04151
	mTOR signaling pathway			hsa04150
Cell Process	Cell apoptosis
In-vitro Model	HEK293T	Normal	Homo sapiens	CVCL_0063
In-vivo Model	Specifically, rats were anesthetized with an intraperitoneal injection of 4% pentobarbital sodium (35 mg/kg) after weight measurement. To expose the posterior vertebral arch from T8 to T12, an incision was subsequently made on the skin along the dorsomedial line to the aponeurosis and muscle plane. Laminectomy (3 mm) was performed from the caudal end of the T10 vertebra to the caudal end of the T11 vertebra under a dissection stereomicroscope. Infinite Horizons impactor (Infinite Horizons, L.L.C., Lexington, KY, USA) was utilized to induce contusion SCI at the force of 60 kdyn/cm . The incision was sutured, followed by intramuscular injection of 20000 units of penicillin once a day for three days. Incisions of rats in the sham group (N = 10) were sutured after skin incision without modeling surgery and related treatment. SCI rat model was established and SCI rats were assigned to the following groups (N = 10 per group): SCI group (SCI treatment), SCI + sh-NC group (injected with silencing negative control lentivirus after SCI treatment), SCI + sh-METTL14 + sh-EEF1A2 group (injected with silencing EEF1A2 and silencing METTL14 lentivirus after SCI treatment), SCI + oe-NC group (injected with overexpressed EEF1A2 NC lentivirus after SCI treatment), SCI + oe-EEF1A2 group (injected with overexpressed EEF1A2 lentivirus after SCI treatment), SCI + oe-EEF1A2 + H2O group [injected with overexpressed EEF1A2 lentivirus and treated with 50 mg/kg (i.p.) H2O after SCI treatment] and SCI + oe-EEF1A2 + Perifosine group [injected with overexpressed EEF1A2 lentivirus and treated with 50 mg/kg (i.p.) Perifosine after SCI treatment . Lentivirus treatment was conducted three days following laminectomy (on day 0, 1, and 2). sh-NC, sh-METTL14, sh-EEF1A2, oe-NC, and oe-EEF1A2 lentivirus (50 uL/day, 100 nmoL/mL; RiboBio, Guangzhou, China) were intrathecally injected through lumbar puncture for 15 min per day.
Response Summary	Silencing METTL14 repressed apoptosis of spinal cord neurons and attenuated spinal cord injury by inhibiting m6A modification of Elongation factor 1-alpha 2 (EEF1A2) and activating the Akt/mTOR pathway.

Engulfment and cell motility protein 1 (ELMO1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL14*
Cell Line	HepG2 cell line	Homo sapiens
Treatment: shMETTL14 HepG2 cells Control: shCtrl HepG2 cells		GSE121949
Regulation		logFC: 2.58E+00 p-value: 2.13E-02
More Results	Click to View More RNA-seq Results

Inflammatory spondyloarthritis [ICD-11: FA92]

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	Ankylosing spondylitis [ICD-11: FA92.0Z]
Target Regulation	Up regulation
Pathway Response	RNA degradation			hsa03018
Cell Process	RNA stability
In-vitro Model	HEK293T	Normal	Homo sapiens	CVCL_0063
In-vivo Model	The SKG mice were randomly divided into three groups: a PBS group, an Av-NC group, and an Av-ELMO1 group. The SKG mice in the Av-ELMO1 group were treated with 5 × 10¹⁰ Av-ELMO1 via intravenous tail vein injection at the time of disease induction, and the SKG mice in the Av-NC group or PBS group were separately treated with equal amounts of control adenoviruses or PBS.
Response Summary	TNF-alpha leads to increased expression of ELMO1 in AS-MSC, which is mediated by a METTL14 dependent m6A modification in Engulfment and cell motility protein 1 (ELMO1) 3'UTR. Higher ELMO1 expression of AS-MSC is found in vivo in AS patients.

Ephrin type-B receptor 2 (ERK/EPHB2)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL14*
Cell Line	MDA-MB-231	Homo sapiens
Treatment: siMETTL14 MDA-MB-231 cells Control: MDA-MB-231 cells		GSE81164
Regulation		logFC: -7.89E-01 p-value: 4.97E-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				[19]
Responsed Disease	Muscular dystrophies [ICD-11: 8C70]
Target Regulation	Up regulation
Pathway Response	MAPK signaling pathway			hsa04010
In-vitro Model	HEK293T	Normal	Homo sapiens	CVCL_0063
In-vitro Model	C2C12	Normal	Mus musculus	CVCL_0188
In-vivo Model	For mouse muscle injury and regeneration experiment, tibialis anterior (TA) muscles of 6-week-old male mice were injected with 25 uL of 10 uM cardiotoxin (CTX, Merck Millipore, 217503), 0.9% normal saline (Saline) were used as control. The regenerated muscles were collected at day 1, 3, 5, and 10 post-injection. TA muscles were isolated for Hematoxylin and eosin staining or frozen in liquid nitrogen for RNA and protein extraction.
Response Summary	m6A writers METTL3/METTL14 and the m6A reader YTHDF1 orchestrate MNK2 expression posttranscriptionally and thus control Ephrin type-B receptor 2 (ERK/EPHB2) signaling, which is required for the maintenance of muscle myogenesis and contributes to regeneration.

Epidermal growth factor receptor (EGFR)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL14*
Cell Line	HepG2 cell line	Homo sapiens
Treatment: shMETTL14 HepG2 cells Control: shCtrl HepG2 cells		GSE121949
Regulation		logFC: 1.00E+00 p-value: 2.28E-08
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				[20]
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulation	Down regulation
Pathway Response	PI3K-Akt signaling pathway			hsa04151
Cell Process	Epithelial-mesenchymal transition
In-vitro Model	YY-8103	Adult hepatocellular carcinoma	Homo sapiens	CVCL_WY40
	SMMC-7721	Endocervical adenocarcinoma	Homo sapiens	CVCL_0534
	HCCLM3	Adult hepatocellular carcinoma	Homo sapiens	CVCL_6832
	L-02	Endocervical adenocarcinoma	Homo sapiens	CVCL_6926
	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
	Hep 3B2.1-7	Childhood hepatocellular carcinoma	Homo sapiens	CVCL_0326
In-vivo Model	For the lung metastasis model, stably transfected HepG2 cells (1 × 10⁶/0.1 mL DMEM) were injected into each nude mouse through the tail vein. Five weeks later, mice were euthanized, and the lung tissues were collected.
Response Summary	METTL14 was found to inhibit HCC cell migration, invasion, and EMT through modulating Epidermal growth factor receptor (EGFR)/PI3K/AKT signaling pathway in an m6A-dependent manner.

Eukaryotic translation initiation factor 4 gamma 1 (EIF4G1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL14*
Cell Line	Embryonic stem cells	Mus musculus
Treatment: METTL14 knockout mESCs Control: Wild type mESCs		GSE156481
Regulation		logFC: -6.00E-01 p-value: 2.49E-44
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				[21]
Responsed Disease	Oral squamous cell carcinoma [ICD-11: 2B6E.0]
Target Regulation	Down regulation
Pathway Response	Autophagy			hsa04140
Cell Process	Cell autophagy
In-vitro Model	CAL-33	Tongue squamous cell carcinoma	Homo sapiens	CVCL_1108
	HN-6	Tongue squamous cell carcinoma	Homo sapiens	CVCL_8129
	HSC-3	Tongue squamous cell carcinoma	Homo sapiens	CVCL_1288
In-vivo Model	Specific pathogen-free (SPF) female NOD/SCID mice (5-6 weeks old) were randomly distributed into two groups: the OECtrl group and the OEMETTL14 groups. Phosphate buffer (200 uL) containing approximately 5 × 10⁷ HSC3 or CAL33 cells was subcutaneously injected into the inner thigh of each mouse. The mice were euthanized two weeks after injection, and the tumour xenografts were harvested, photographed, weighed, and fixed.
Response Summary	The study identified the mechanism by which rapamycin affects autophagy via regulating METTL14, which provides a new idea for a potential targeted therapy for oral squamous cell carcinoma. METTL14 mediated Eukaryotic translation initiation factor 4 gamma 1 (EIF4G1) expression via m6A modification and regulated autophagy levels and biological functions in oral squamous cell carcinoma.

Fibroblast growth factor receptor 4 (FGFR4)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL14*
Cell Line	HepG2 cell line	Homo sapiens
Treatment: shMETTL14 HepG2 cells Control: shCtrl HepG2 cells		GSE121949
Regulation		logFC: -7.17E-01 p-value: 3.71E-06
More Results	Click to View More RNA-seq Results

Breast cancer [ICD-11: 2C60]

In total 3 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[8]
Responsed Disease	Breast cancer [ICD-11: 2C60]
Responsed Drug	Pertuzumab		Approved	Drug Info
Target Regulation	Down regulation
Pathway Response	Wnt signaling pathway			hsa04310
Cell Process	Glutathione synthesis
In-vitro Model	ZR-75-1	Invasive breast carcinoma	Homo sapiens	CVCL_0588
	T-47D	Invasive breast carcinoma	Homo sapiens	CVCL_0553
	SUM-159 (A mesenchymal triple-negative breast cancer cell line)
	SK-BR-3	Breast adenocarcinoma	Homo sapiens	CVCL_0033
	MDA-MB-468	Breast adenocarcinoma	Homo sapiens	CVCL_0419
	MDA-MB-453	Breast adenocarcinoma	Homo sapiens	CVCL_0418
	MDA-MB-361	Breast adenocarcinoma	Homo sapiens	CVCL_0620
	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
	HEK293T	Normal	Homo sapiens	CVCL_0063
	BT-549	Invasive breast carcinoma	Homo sapiens	CVCL_1092
	BT-474	Invasive breast carcinoma	Homo sapiens	CVCL_0179
	AU565	Breast adenocarcinoma	Homo sapiens	CVCL_1074
In-vivo Model	Luciferase-labeled rSKBR3 and MDA-MB-361 cells (1 × 10⁷ cells) mixed with 1:1 Matrigel (Corning, 356237) were subcutaneously injected into the fat pads of mice. After a tumor was palpable, the mice were randomized into four groups (five mice per group), and they were treated with vehicle, trastuzumab (20 mg/kg, intraperitoneal administration), roblitinib (30 mg/kg, oral administration), or a combination of both drugs.
Response Summary	m6A-hypomethylation regulated Fibroblast growth factor receptor 4 (FGFR4) phosphorylates GSK-3beta and activates beta-catenin/TCF4-SLC7A11/FPN1 signaling to drive anti-HER2 resistance. Knockdown of METTL14 significantly increased the expression level of FGFR4 in HER2-positive breast cancer cells. FGFR4 reduced the sensitivity of HER2-positive breast cancer to trastuzumab plus pertuzumab or tucatinib. These results pinpoint a mechanism of anti-HER2 resistance and provide a strategy for overcoming resistance via FGFR4 inhibition in recalcitrant HER2-positive breast cancer.
Experiment 2 Reporting the m6A-centered Disease Response of This Target Gene				[8]
Responsed Disease	Breast cancer [ICD-11: 2C60]
Responsed Drug	Trastuzumab		Approved	Drug Info
Target Regulation	Down regulation
Pathway Response	Wnt signaling pathway			hsa04310
Cell Process	Glutathione synthesis
In-vitro Model	ZR-75-1	Invasive breast carcinoma	Homo sapiens	CVCL_0588
	T-47D	Invasive breast carcinoma	Homo sapiens	CVCL_0553
	SUM-159 (A mesenchymal triple-negative breast cancer cell line)
	SK-BR-3	Breast adenocarcinoma	Homo sapiens	CVCL_0033
	MDA-MB-468	Breast adenocarcinoma	Homo sapiens	CVCL_0419
	MDA-MB-453	Breast adenocarcinoma	Homo sapiens	CVCL_0418
	MDA-MB-361	Breast adenocarcinoma	Homo sapiens	CVCL_0620
	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
	HEK293T	Normal	Homo sapiens	CVCL_0063
	BT-549	Invasive breast carcinoma	Homo sapiens	CVCL_1092
	BT-474	Invasive breast carcinoma	Homo sapiens	CVCL_0179
	AU565	Breast adenocarcinoma	Homo sapiens	CVCL_1074
In-vivo Model	Luciferase-labeled rSKBR3 and MDA-MB-361 cells (1 × 10⁷ cells) mixed with 1:1 Matrigel (Corning, 356237) were subcutaneously injected into the fat pads of mice. After a tumor was palpable, the mice were randomized into four groups (five mice per group), and they were treated with vehicle, trastuzumab (20 mg/kg, intraperitoneal administration), roblitinib (30 mg/kg, oral administration), or a combination of both drugs.
Response Summary	m6A-hypomethylation regulated Fibroblast growth factor receptor 4 (FGFR4) phosphorylates GSK-3beta and activates beta-catenin/TCF4-SLC7A11/FPN1 signaling to drive anti-HER2 resistance. Knockdown of METTL14 significantly increased the expression level of FGFR4 in HER2-positive breast cancer cells. FGFR4 reduced the sensitivity of HER2-positive breast cancer to trastuzumab plus pertuzumab or tucatinib. These results pinpoint a mechanism of anti-HER2 resistance and provide a strategy for overcoming resistance via FGFR4 inhibition in recalcitrant HER2-positive breast cancer.
Experiment 3 Reporting the m6A-centered Disease Response of This Target Gene				[8]
Responsed Disease	Breast cancer [ICD-11: 2C60]
Responsed Drug	Tucatinib		Approved	Drug Info
Target Regulation	Down regulation
Pathway Response	Wnt signaling pathway			hsa04310
Cell Process	Glutathione synthesis
In-vitro Model	ZR-75-1	Invasive breast carcinoma	Homo sapiens	CVCL_0588
	T-47D	Invasive breast carcinoma	Homo sapiens	CVCL_0553
	SUM-159 (A mesenchymal triple-negative breast cancer cell line)
	SK-BR-3	Breast adenocarcinoma	Homo sapiens	CVCL_0033
	MDA-MB-468	Breast adenocarcinoma	Homo sapiens	CVCL_0419
	MDA-MB-453	Breast adenocarcinoma	Homo sapiens	CVCL_0418
	MDA-MB-361	Breast adenocarcinoma	Homo sapiens	CVCL_0620
	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
	HEK293T	Normal	Homo sapiens	CVCL_0063
	BT-549	Invasive breast carcinoma	Homo sapiens	CVCL_1092
	BT-474	Invasive breast carcinoma	Homo sapiens	CVCL_0179
	AU565	Breast adenocarcinoma	Homo sapiens	CVCL_1074
In-vivo Model	Luciferase-labeled rSKBR3 and MDA-MB-361 cells (1 × 10⁷ cells) mixed with 1:1 Matrigel (Corning, 356237) were subcutaneously injected into the fat pads of mice. After a tumor was palpable, the mice were randomized into four groups (five mice per group), and they were treated with vehicle, trastuzumab (20 mg/kg, intraperitoneal administration), roblitinib (30 mg/kg, oral administration), or a combination of both drugs.
Response Summary	m6A-hypomethylation regulated Fibroblast growth factor receptor 4 (FGFR4) phosphorylates GSK-3beta and activates beta-catenin/TCF4-SLC7A11/FPN1 signaling to drive anti-HER2 resistance. Knockdown of METTL14 significantly increased the expression level of FGFR4 in HER2-positive breast cancer cells. FGFR4 reduced the sensitivity of HER2-positive breast cancer to trastuzumab plus pertuzumab or tucatinib. These results pinpoint a mechanism of anti-HER2 resistance and provide a strategy for overcoming resistance via FGFR4 inhibition in recalcitrant HER2-positive breast cancer.

Forkhead box protein O1 (FOXO1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL14*
Cell Line	MDA-MB-231	Homo sapiens
Treatment: siMETTL14 MDA-MB-231 cells Control: MDA-MB-231 cells		GSE81164
Regulation		logFC: -7.56E-01 p-value: 2.27E-07
More Results	Click to View More RNA-seq Results

Herpes infection [ICD-11: 1F00]

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	Herpes infection [ICD-11: 1F00]
Target Regulation	Up regulation
Pathway Response	FoxO signaling pathway			hsa04068
In-vitro Model	HUVEC-C	Normal	Homo sapiens	CVCL_2959
In-vivo Model	METTL14^+/- mice are generated by mating wild-type mice (C57/BL6 background) with METTL14^+/- mice. METTL14^+/-/APOE^-/- healthy offspring mice are produced by heterozygous METTL14^+/- mice and heterozygous APOE^-/- mice by Mendelian ratios. APOE^-/- mice and C57/BL6 mice were purchased from Model Animal Research Center of Nanjing (Nanjing, Jiangsu, China). All mice were housed in the Laboratory Animals Center of the Henan Provincial People's Hospital, with controlled temperature and humidity and a 12:12-hour dark-light cycle, and were provided water and mouse chow ad libitum.
Response Summary	METTL14 promotes Forkhead box protein O1 (FOXO1) expression by enhancing its m6A modification and inducing endothelial cell inflammatory response as well as atherosclerotic plaque formation.

Atherosclerosis [ICD-11: BD40]

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	Atherosclerosis [ICD-11: BD40.Z]
Target Regulation	Up regulation
Pathway Response	FoxO signaling pathway			hsa04068
In-vitro Model	HUVEC-C	Normal	Homo sapiens	CVCL_2959
In-vivo Model	Mettl14^-/+ mice are generated by mating wild-type mice (C57/BL6 background) with Mettl14^-/+ mice. Mettl14^-/+/APOE^-/- healthy offspring mice are produced by heterozygous Mettl14^-/+ mice and heterozygous APOE^-/- mice by Mendelian ratios. APOE^-/- mice and C57/BL6 mice were purchased from Model Animal Research Center of Nanjing (Nanjing, Jiangsu, China). All mice were housed in the Laboratory Animals Center of the Henan Provincial People's Hospital, with controlled temperature and humidity and a 12:12-hour dark-light cycle, and were provided water and mouse chow ad libitum.
Response Summary	METTL14 promotes Forkhead box protein O1 (FOXO1) expression by enhancing its m6A modification and inducing endothelial cell inflammatory response as well as atherosclerotic plaque formation.

Forkhead box protein O3 (FOXO3)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL14*
Cell Line	MDA-MB-231	Homo sapiens
Treatment: siMETTL14 MDA-MB-231 cells Control: MDA-MB-231 cells		GSE81164
Regulation		logFC: -1.48E+00 p-value: 5.68E-29
More Results	Click to View More RNA-seq Results

Pre-eclampsia [ICD-11: JA24]

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	Pre-eclampsia [ICD-11: JA24]
Target Regulation	Up regulation
Cell Process	Cell autophagy
In-vitro Model	HTR-8/SVneo	Normal	Homo sapiens	CVCL_7162
In-vitro Model	HTR-8	Normal	Homo sapiens	CVCL_D728
Response Summary	Global RNA m6A methylation and METTL14 expression were significantly increased in placental tissues obtained from patients with preeclampsia. Forkhead box protein O3 (FOXO3) inhibition effectively prevented the impairment of trophoblast proliferation and invasion, and diminished the induction of trophoblast autophagy and apoptosis in METTL14-overexpressing HTR-8/SVneo cells.

Inflammatory spondyloarthritis [ICD-11: FA92]

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	Ankylosing spondylitis [ICD-11: FA92.0Z]
Target Regulation	Up regulation
In-vitro Model	Jurkat	T acute lymphoblastic leukemia	Homo sapiens	CVCL_0065

Glycogen synthase kinase-3 beta (GSK3Beta/GSK3B)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL14*
Cell Line	BMDM	Mus musculus
Treatment: METTL14 knockout mice BMDM Control: Wild type mice BMDM		GSE153512
Regulation		logFC: 1.08E+00 p-value: 1.69E-24
More Results	Click to View More RNA-seq Results

Breast cancer [ICD-11: 2C60]

In total 3 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[8]
Responsed Disease	Breast cancer [ICD-11: 2C60]
Responsed Drug	Pertuzumab		Approved	Drug Info
Target Regulation	Down regulation
Pathway Response	Wnt signaling pathway			hsa04310
Cell Process	Glutathione synthesis
In-vitro Model	ZR-75-1	Invasive breast carcinoma	Homo sapiens	CVCL_0588
	T-47D	Invasive breast carcinoma	Homo sapiens	CVCL_0553
	SUM-159 (A mesenchymal triple-negative breast cancer cell line)
	SK-BR-3	Breast adenocarcinoma	Homo sapiens	CVCL_0033
	MDA-MB-468	Breast adenocarcinoma	Homo sapiens	CVCL_0419
	MDA-MB-453	Breast adenocarcinoma	Homo sapiens	CVCL_0418
	MDA-MB-361	Breast adenocarcinoma	Homo sapiens	CVCL_0620
	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
	HEK293T	Normal	Homo sapiens	CVCL_0063
	BT-549	Invasive breast carcinoma	Homo sapiens	CVCL_1092
	BT-474	Invasive breast carcinoma	Homo sapiens	CVCL_0179
	AU565	Breast adenocarcinoma	Homo sapiens	CVCL_1074
In-vivo Model	Luciferase-labeled rSKBR3 and MDA-MB-361 cells (1 × 10⁷ cells) mixed with 1:1 Matrigel (Corning, 356237) were subcutaneously injected into the fat pads of mice. After a tumor was palpable, the mice were randomized into four groups (five mice per group), and they were treated with vehicle, trastuzumab (20 mg/kg, intraperitoneal administration), roblitinib (30 mg/kg, oral administration), or a combination of both drugs.
Response Summary	m6A-hypomethylation regulated FGFR4 phosphorylates Glycogen synthase kinase-3 beta (GSK3Beta/GSK3B) and activates beta-catenin/TCF4-SLC7A11/FPN1 signaling to drive anti-HER2 resistance. Knockdown of METTL14 significantly increased the expression level of FGFR4 in HER2-positive breast cancer cells. FGFR4 reduced the sensitivity of HER2-positive breast cancer to trastuzumab plus pertuzumab or tucatinib. These results pinpoint a mechanism of anti-HER2 resistance and provide a strategy for overcoming resistance via FGFR4 inhibition in recalcitrant HER2-positive breast cancer.
Experiment 2 Reporting the m6A-centered Disease Response of This Target Gene				[8]
Responsed Disease	Breast cancer [ICD-11: 2C60]
Responsed Drug	Trastuzumab		Approved	Drug Info
Target Regulation	Down regulation
Pathway Response	Wnt signaling pathway			hsa04310
Cell Process	Glutathione synthesis
In-vitro Model	ZR-75-1	Invasive breast carcinoma	Homo sapiens	CVCL_0588
	T-47D	Invasive breast carcinoma	Homo sapiens	CVCL_0553
	SUM-159 (A mesenchymal triple-negative breast cancer cell line)
	SK-BR-3	Breast adenocarcinoma	Homo sapiens	CVCL_0033
	MDA-MB-468	Breast adenocarcinoma	Homo sapiens	CVCL_0419
	MDA-MB-453	Breast adenocarcinoma	Homo sapiens	CVCL_0418
	MDA-MB-361	Breast adenocarcinoma	Homo sapiens	CVCL_0620
	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
	HEK293T	Normal	Homo sapiens	CVCL_0063
	BT-549	Invasive breast carcinoma	Homo sapiens	CVCL_1092
	BT-474	Invasive breast carcinoma	Homo sapiens	CVCL_0179
	AU565	Breast adenocarcinoma	Homo sapiens	CVCL_1074
In-vivo Model	Luciferase-labeled rSKBR3 and MDA-MB-361 cells (1 × 10⁷ cells) mixed with 1:1 Matrigel (Corning, 356237) were subcutaneously injected into the fat pads of mice. After a tumor was palpable, the mice were randomized into four groups (five mice per group), and they were treated with vehicle, trastuzumab (20 mg/kg, intraperitoneal administration), roblitinib (30 mg/kg, oral administration), or a combination of both drugs.
Response Summary	m6A-hypomethylation regulated FGFR4 phosphorylates Glycogen synthase kinase-3 beta (GSK3Beta/GSK3B) and activates beta-catenin/TCF4-SLC7A11/FPN1 signaling to drive anti-HER2 resistance. Knockdown of METTL14 significantly increased the expression level of FGFR4 in HER2-positive breast cancer cells. FGFR4 reduced the sensitivity of HER2-positive breast cancer to trastuzumab plus pertuzumab or tucatinib. These results pinpoint a mechanism of anti-HER2 resistance and provide a strategy for overcoming resistance via FGFR4 inhibition in recalcitrant HER2-positive breast cancer.
Experiment 3 Reporting the m6A-centered Disease Response of This Target Gene				[8]
Responsed Disease	Breast cancer [ICD-11: 2C60]
Responsed Drug	Tucatinib		Approved	Drug Info
Target Regulation	Down regulation
Pathway Response	Wnt signaling pathway			hsa04310
Cell Process	Glutathione synthesis
In-vitro Model	ZR-75-1	Invasive breast carcinoma	Homo sapiens	CVCL_0588
	T-47D	Invasive breast carcinoma	Homo sapiens	CVCL_0553
	SUM-159 (A mesenchymal triple-negative breast cancer cell line)
	SK-BR-3	Breast adenocarcinoma	Homo sapiens	CVCL_0033
	MDA-MB-468	Breast adenocarcinoma	Homo sapiens	CVCL_0419
	MDA-MB-453	Breast adenocarcinoma	Homo sapiens	CVCL_0418
	MDA-MB-361	Breast adenocarcinoma	Homo sapiens	CVCL_0620
	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
	HEK293T	Normal	Homo sapiens	CVCL_0063
	BT-549	Invasive breast carcinoma	Homo sapiens	CVCL_1092
	BT-474	Invasive breast carcinoma	Homo sapiens	CVCL_0179
	AU565	Breast adenocarcinoma	Homo sapiens	CVCL_1074
In-vivo Model	Luciferase-labeled rSKBR3 and MDA-MB-361 cells (1 × 10⁷ cells) mixed with 1:1 Matrigel (Corning, 356237) were subcutaneously injected into the fat pads of mice. After a tumor was palpable, the mice were randomized into four groups (five mice per group), and they were treated with vehicle, trastuzumab (20 mg/kg, intraperitoneal administration), roblitinib (30 mg/kg, oral administration), or a combination of both drugs.
Response Summary	m6A-hypomethylation regulated FGFR4 phosphorylates Glycogen synthase kinase-3 beta (GSK3Beta/GSK3B) and activates beta-catenin/TCF4-SLC7A11/FPN1 signaling to drive anti-HER2 resistance. Knockdown of METTL14 significantly increased the expression level of FGFR4 in HER2-positive breast cancer cells. FGFR4 reduced the sensitivity of HER2-positive breast cancer to trastuzumab plus pertuzumab or tucatinib. These results pinpoint a mechanism of anti-HER2 resistance and provide a strategy for overcoming resistance via FGFR4 inhibition in recalcitrant HER2-positive breast cancer.

Heat shock 70 kDa protein 1A (HSPA1A)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL14*
Cell Line	BMDM	Mus musculus
Treatment: METTL14 knockout mice BMDM Control: Wild type mice BMDM		GSE153512
Regulation		logFC: 1.20E+00 p-value: 8.44E-04
More Results	Click to View More RNA-seq Results

Pre-eclampsia [ICD-11: JA24]

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	Pre-eclampsia [ICD-11: JA24]
Target Regulation	Up regulation
Pathway Response	Wnt signaling pathway	hsa04310
	mTOR signaling pathway	hsa04150
Response Summary	Findings show that METTL3 and METTL14 were up-regulated in preeclampsia(PE). Heat shock 70 kDa protein 1A (HSPA1A) is involved in the pathophysiology of PE as its mRNA and protein expression is regulated by m6A modification.

Hepatocyte nuclear factor 3-gamma (HNF3gamma/FOXA3)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL14*
Cell Line	mouse embryonic stem cells	Mus musculus
Treatment: METTL14-/- ESCs Control: Wild type ESCs		GSE145309
Regulation		logFC: -4.46E+00 p-value: 6.08E-19
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				[25]
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Responsed Drug	Sorafenib		Approved	Drug Info
Target Regulation	Down regulation
Cell Process	Membrane transport
	Cell apoptosis
In-vitro Model	HCCLM3	Adult hepatocellular carcinoma	Homo sapiens	CVCL_6832
	Huh-7	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0336
In-vivo Model	When xenografted tumor growth reached 500 mm³, the mice were subjected to intratumoral injection of Ad-con or Ad-HNF3γ every other day. For the PDX model, fresh patient HCC tissues were cut into fragments with a volume of 3 × 3 mm³ and then implanted subcutaneously into the flanks of nude mice. The mice were given sorafenib (30 mg/kg) or vehicle orally twice a week for 24 days.
Response Summary	The Hepatocyte nuclear factor 3-gamma (HNF3gamma/FOXA3) reduction in hepatocellular carcinoma could be mediated by METTL14-dependent m6A methylation of HNF3-Gamma mRNA. HNF3-Gamma plays an essential role in HCC differentiation and serves as a therapeutic target and predictor of sorafenib benefit in patients.

Insulin-like growth factor I (IGF1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL14*
Cell Line	BMDM	Mus musculus
Treatment: METTL14 knockout mice BMDM Control: Wild type mice BMDM		GSE153512
Regulation		logFC: -7.37E-01 p-value: 4.88E-20
More Results	Click to View More RNA-seq Results

Ageing-related disease [ICD-11: 9B10-9B60]

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	Ageing-related disease [ICD-11: 9B10-9B60]
Target Regulation	Up regulation
Pathway Response	Nucleotide excision repair	hsa03420
Cell Process	DNA repair and mitochondrial stress
In-vitro Model	Mouse fibroblasts (Major cellular components of loose connective tissue)
Response Summary	The long-lived endocrine mutants - Snell dwarf, growth hormone receptor deletion and pregnancy-associated plasma protein-A knockout - all show increases in the N6-adenosine-methyltransferases (METTL3/14) that catalyze 6-methylation of adenosine (m6A) in the 5' UTR region of select mRNAs. In addition, these mice have elevated levels of YTHDF1, which recognizes m6A and promotes translation by a cap-independent mechanism. Augmented translation by cap-independent pathways facilitated by m6A modifications contribute to the stress resistance and increased healthy longevity of mice with diminished GH and Insulin-like growth factor I (IGF1) signals.

Integrin beta-4 (ITGB4)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL14*
Cell Line	HepG2 cell line	Homo sapiens
Treatment: shMETTL14 HepG2 cells Control: shCtrl HepG2 cells		GSE121949
Regulation		logFC: 6.11E-01 p-value: 3.31E-02
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				[27]
Responsed Disease	Renal cell carcinoma of kidney [ICD-11: 2C90.0]
Target Regulation	Down regulation
Pathway Response	PI3K-Akt signaling pathway			hsa04151
Cell Process	Epithelial-mesenchymal transition
In-vitro Model	OS-RC-2	Clear cell renal cell carcinoma	Homo sapiens	CVCL_1626
	786-O	Renal cell carcinoma	Homo sapiens	CVCL_1051
	769-P	Renal cell carcinoma	Homo sapiens	CVCL_1050
In-vivo Model	Each group included 3 mice. 1.0 × 10⁶ stably transfected ACHN cells in 150 uL were injected into a tail vein of each mouse, 45 days after which lungs were excised from the sacrificed mice and stained by Hematoxylin and Eosin (HE) Staining.
Response Summary	Knockdown of METTL14 promoted ccRCC cell migration, invasiveness and metastasis as well as stimulating the EMT process and the PI3K/AKT signal by overexpressing Integrin beta-4 (ITGB4).

Interferon beta (IFNB1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL14*
Cell Line	Neural progenitor cell line	Mus musculus
Treatment: METTL14 knockout NPCs Control: Wild type NPCs		GSE158985
Regulation		logFC: 7.66E-01 p-value: 2.22E-04
More Results	Click to View More RNA-seq Results

Papillomaviruses [ICD-11: 1D9Z]

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	Unspecified viral infection [ICD-11: 1D9Z]
Target Regulation	Down regulation
Pathway Response	Cellular senescence			hsa04218
Cell Process	Metabolic reprogramming
	Stress responses
	Aging
In-vitro Model	BSC40	Normal	Chlorocebus pygerythrus	CVCL_3656
	HCMV AD169GFP (Human cytomegalovirus)
	NHDF (Primary Normal Human Dermal Fibroblasts)
	Vero	Normal	Chlorocebus sabaeus	CVCL_0059
Response Summary	Responses to nonmicrobial dsDNA in uninfected cells, which shape host immunity and contribute to autoimmune disease, are regulated by enzymes controlling m6A epitranscriptomic changes. While METTL14 depletion reduced virus reproduction and stimulated dsDNA- or HCMV-induced Interferon beta (IFNB1) mRNA accumulation, ALKBH5 depletion had the opposite effect.

Innate immunity [ICD-11: 4A00]

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	Innate immunity [ICD-11: 4A00]
Target Regulation	Down regulation
Pathway Response	Cellular senescence			hsa04218
Cell Process	Metabolic reprogramming
	Stress responses
	Aging
In-vitro Model	BSC40	Normal	Chlorocebus pygerythrus	CVCL_3656
	HCMV AD169GFP (Human cytomegalovirus)
	NHDF (Primary Normal Human Dermal Fibroblasts)
	Vero	Normal	Chlorocebus sabaeus	CVCL_0059
Response Summary	Responses to nonmicrobial dsDNA in uninfected cells, which shape host immunity and contribute to autoimmune disease, are regulated by enzymes controlling m6A epitranscriptomic changes. While METTL14 depletion reduced virus reproduction and stimulated dsDNA- or HCMV-induced Interferon beta (IFNB1) mRNA accumulation, ALKBH5 depletion had the opposite effect.

Interferon gamma (IFN-gamma)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL14*
Cell Line	CT26 cell line	Mus musculus
Treatment: METTL14 knockout CT26 cells Control: CT26 cells		GSE142589
Regulation		logFC: 1.52E+00 p-value: 1.96E-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				[5]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulation	Down regulation
Pathway Response	PD-L1 expression and PD-1 checkpoint pathway in cancer			hsa05235
Cell Process	Immunity
In-vitro Model	CT26	Mouse colon adenocarcinoma	Mus musculus	CVCL_7254
	B16-GM-CSF (B16-GM-CSF cell line was a kind gift from Drs. Glenn Dranoff and Michael Dougan (Dana-Farber/Harvard Cancer Center))
	B16-F10	Mouse melanoma	Mus musculus	CVCL_0159
In-vivo Model	2 × 10⁶ CT26 cells with knockout of Mettl3, Mettl14, Mettl3/Stat1, Mettl3/Irf1, Mettl14/Stat1, or Mettl14/Irf1 and control were suspended in 200 uL of PBS/Matrigel (Corning) (1:1) and then subcutaneously inoculated into flank of each mouse.
Response Summary	In colorectal cancer, Mettl3- or Mettl14-deficient tumors increased cytotoxic tumor-infiltrating CD8+ T cells and elevated secretion of Interferon gamma (IFN-gamma), Cxcl9, and Cxcl10 in tumor microenvironment in vivo. Mechanistically, Mettl3 or Mettl14 loss promoted IFN-gamma-Stat1-Irf1 signaling through stabilizing the Stat1 and Irf1 mRNA via Ythdf2.

Interferon regulatory factor 1 (Irf1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL14*
Cell Line	CT26 cell line	Mus musculus
Treatment: METTL14 knockout CT26 cells Control: CT26 cells		GSE142589
Regulation		logFC: 1.58E+00 p-value: 1.17E-04
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				[5]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulation	Down regulation
Pathway Response	PD-L1 expression and PD-1 checkpoint pathway in cancer			hsa05235
Cell Process	Immunity
In-vitro Model	CT26	Mouse colon adenocarcinoma	Mus musculus	CVCL_7254
	B16-GM-CSF (B16-GM-CSF cell line was a kind gift from Drs. Glenn Dranoff and Michael Dougan (Dana-Farber/Harvard Cancer Center))
	B16-F10	Mouse melanoma	Mus musculus	CVCL_0159
In-vivo Model	2 × 10⁶ CT26 cells with knockout of Mettl3, Mettl14, Mettl3/Stat1, Mettl3/Irf1, Mettl14/Stat1, or Mettl14/Irf1 and control were suspended in 200 uL of PBS/Matrigel (Corning) (1:1) and then subcutaneously inoculated into flank of each mouse.
Response Summary	In colorectal cancer, Mettl3- or Mettl14-deficient tumors increased cytotoxic tumor-infiltrating CD8+ T cells and elevated secretion of IFN-gamma, Cxcl9, and Cxcl10 in tumor microenvironment in vivo. Mechanistically, Mettl3 or Mettl14 loss promoted IFN-gamma-Stat1-Irf1 signaling through stabilizing the Stat1 and Interferon regulatory factor 1 (Irf1) mRNA via Ythdf2.

Interleukin-6 (IL-6)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL14*
Cell Line	MDA-MB-231	Homo sapiens
Treatment: siMETTL14 MDA-MB-231 cells Control: MDA-MB-231 cells		GSE81164
Regulation		logFC: 1.55E+00 p-value: 4.20E-30
More Results	Click to View More RNA-seq Results

Atherosclerosis [ICD-11: BD40]

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	Atherosclerosis [ICD-11: BD40.Z]
Target Regulation	Up regulation
Pathway Response	IL-17 signaling pathway			hsa04657
In-vitro Model	THP-1	Childhood acute monocytic leukemia	Homo sapiens	CVCL_0006
In-vivo Model	Mettl14 heterozygous mice (Mettl14^-/+) were established from C57/BL6 mice by Cyagen Biosciences, Inc. (Suzhou, Jiangsu, China), using CRISPR/Cas9-based targeting and homology-directed repair. C57/BL6 and APOE^-/- mice were purchased from Beijing Vital River Laboratory Animal Technology (Beijing, China). Mettl14^-/+APOE^-/- mice were generated by breeding Mettl14^-/+ mice with APOE^-/- mice. Eight- to 10-week-old male APOE^-/- (WT) mice and Mettl14^-/+APOE^-/- (KO) mice were fed a high-cholesterol diet (D12108C, Opensource diets) for 12 weeks. Then, the mice were euthanized for further analysis.
Response Summary	Mettl14 gene knockout significantly reduced the inflammatory response of macrophages and the development of atherosclerotic plaques, Mettl14 plays a vital role in macrophage inflammation in atherosclerosis via the NF-Kappa-B/Interleukin-6 (IL-6) signaling pathway.

Krueppel-like factor 4 (KLF4)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL14*
Cell Line	MDA-MB-231	Homo sapiens
Treatment: siMETTL14 MDA-MB-231 cells Control: MDA-MB-231 cells		GSE81164
Regulation		logFC: -8.55E-01 p-value: 7.89E-09
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				[30]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulation	Up regulation
In-vitro Model	SW620	Colon adenocarcinoma	Homo sapiens	CVCL_0547
	HT29	Colon cancer	Mus musculus	CVCL_A8EZ
	HCT 8	Colon adenocarcinoma	Homo sapiens	CVCL_2478
In-vivo Model	In vivo, the group of HCT116 cells labeled with luciferase were surgically injected into the spleen of nude mice. After 2 months, the nude mice were subjected to D-luciferin injection and the luciferase signals were monitored and quantified.
Response Summary	The expression of METTL14 was downregulated in CRC cells and METTL14 could inhibit the metastasis of CRC cells. MeCP2 could bind to METTL14 to coregulate tumor suppressor Krueppel-like factor 4 (KLF4) expression through changing m6 A methylation modification.

Meltrin-beta (ADAM19)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL14*
Cell Line	MDA-MB-231	Homo sapiens
Treatment: siMETTL14 MDA-MB-231 cells Control: MDA-MB-231 cells		GSE81164
Regulation		logFC: -1.69E+00 p-value: 2.38E-31
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				[31]
Responsed Disease	Glioblastoma [ICD-11: 2A00.00]
Responsed Drug	Ethyl ester form of meclofenamic acid		Approved	Drug Info
Target Regulation	Down regulation
Cell Process	Cells growth
	Cells self-renewal
	Tumorigenesis
	MicroRNAs in cancer (hsa05206)
In-vitro Model	GSC	Glioma	Epinephelus akaara	CVCL_M752
In-vivo Model	2 × 10⁵ dissociated cells in 2 uL PBS were injected into the following site (anteroposterior [AP] +0.6 mm, mediolateral [ML] +1.6 mm, and dorsoventricular [DV] 2.6 mm) with a rate of 1 uL/min.
Response Summary	Knockdown of METTL3 or METTL14 induced changes in mRNA m6A enrichment and altered mRNA expression of genes (e.g., Meltrin-beta (ADAM19)) with critical biological functions in GSCs. Treatment with MA2, a chemical inhibitor of FTO, dramatically suppressed GSC-induced tumorigenesis and prolonged lifespan in GSC-grafted animals.

Microtubule-associated protein 2 (MAP2)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL14*
Cell Line	mouse embryonic stem cells	Mus musculus
Treatment: METTL14-/- ESCs Control: Wild type ESCs		GSE145309
Regulation		logFC: 3.37E+00 p-value: 1.21E-131
More Results	Click to View More RNA-seq Results

Disorders of the retina [ICD-11: 9B70-9C0Z]

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	Disorders of the retina [ICD-11: 9B70-9C0Z]
Target Regulation	Down regulation
In-vitro Model	ARPE-19	Normal	Homo sapiens	CVCL_0145
Response Summary	The expression of METTL14 is significantly reduced in patients with retinitis pigmentosa (RP). METTL14 regulates the expression of Microtubule-associated protein 2 (MAP2) via the modification of m6A, resulting in the dysregulation of NEUROD1 and pathologic changes in RPE cells.

Mutated in multiple advanced cancers 1 (PTEN)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL14*
Cell Line	HepG2 cell line	Homo sapiens
Treatment: shMETTL14 HepG2 cells Control: shCtrl HepG2 cells		GSE121949
Regulation		logFC: -9.93E-01 p-value: 1.46E-04
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				[33]
Responsed Disease	Gastric cancer [ICD-11: 2B72]
Target Regulation	Up regulation
Cell Process	Cell proliferation
	Cell migration
	Cell invasion
In-vitro Model	RGM1	Normal	Rattus norvegicus	CVCL_0499
	HGC-27	Gastric carcinoma	Homo sapiens	CVCL_1279
	BGC-823	Gastric carcinoma	Homo sapiens	CVCL_3360
	AGS	Gastric adenocarcinoma	Homo sapiens	CVCL_0139
In-vivo Model	For the purpose of enhancing the overall randomization of the experiment, a random comparison table had been employed. Accordingly, 5-wk-old male nude athymic BALB/c nu/nu mice (Slack, Shanghai, China) were randomly divided into two parts including a control group (NC) and the experimental group METTL14-OE. For developing subcutaneous xeno transplantation model, 5 × 10⁶ HGC-27 cells stably transfected with NC or METTL14 overexpression were subcutaneously incorporated for 5-week-old BALB/c nude mice. The mice experienced euthanasia after 27 days of inoculation and obtained xenografts's mass was obtained. Tumor volume over three days was obtained. To create mouse STAD liver metastasis orthotopic tumor model, 1 × 10⁶ HGC-27 cells under stable transfection with NC or METTL14 overexpression were added to subserosal gastric wall of BALB/c nude mice.
Response Summary	METTL14 inhibits tumor growth and metastasis of Stomach Adenocarcinoma via stabilization of Mutated in multiple advanced cancers 1 (PTEN) mRNA expression. Therefore, METTL14 is a potential biomarker of prognosis and therapeutic targets for Stomach Adenocarcinoma.

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		[34]
Responsed Disease	Renal cell carcinoma of kidney [ICD-11: 2C90.0]
Target Regulation	Up regulation
Pathway Response	PI3K-Akt signaling pathway	hsa04151
Response Summary	Upregulation of METTL14 inhibited ccRCC cells proliferation and migration in vitro. Overexpression of METTL14 increased the m6A enrichment of Mutated in multiple advanced cancers 1 (PTEN), and promoted Pten expression. METTL14-enhanced Pten mRNA stability was dependent on YTHDF1.

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				[35]
Responsed Disease	Chronic kidney disease [ICD-11: GB61.Z]
Target Regulation	Down regulation
Pathway Response	PI3K-Akt signaling pathway			hsa04151
Cell Process	Epithelial-mesenchymal transition
In-vitro Model	HK-2 [Human kidney]	Normal	Homo sapiens	CVCL_0302
In-vivo Model	Twenty mice were randomly divided into three groups: normal mice group (N), diabetic mice group (DM), and diabetic mice administrated with TSA group (DM + TSA).
Response Summary	METTL14-regulated PI3K/Akt signaling pathway via Mutated in multiple advanced cancers 1 (PTEN) affected HDAC5-mediated EMT of renal tubular cells in diabetic kidney disease.

Myc proto-oncogene protein (MYC)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL14*
Cell Line	MDA-MB-231	Homo sapiens
Treatment: siMETTL14 MDA-MB-231 cells Control: MDA-MB-231 cells		GSE81164
Regulation		logFC: 1.27E+00 p-value: 6.21E-24
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				[36]
Responsed Disease	Acute myeloid leukaemia [ICD-11: 2A60]
Target Regulation	Up regulation
Cell Process	Cell survival/proliferation
In-vitro Model	HEK293T	Normal	Homo sapiens	CVCL_0063
	HSPC (Human hematopoietic stem cell)
	MNC (Cord blood pluripotent stem cells)
	OP9	Normal	Mus musculus	CVCL_4398
	U-937	Adult acute monocytic leukemia	Homo sapiens	CVCL_0007
In-vivo Model	Lin^- HSPCs were purified from BM of wildtype mice and 0.1×10⁶ cells were seeded in 2 mL OP9 medium onto the OP9 cells with the addition of 10 ng/mL mouse IL-3, 10 ng/mL human IL-6, 10 ng/mL mouse IL-7, 10 ng/mL mouse Flt-3L, and 50 ng/mL mouse stem cell factor (SCF).
Response Summary	METTL14 in normal myelopoiesis and AML pathogenesis, as featured by blocking myeloid differentiation and promoting self-renewal of normal HSPCs and LSCs/LICs. METTL14 exerts its oncogenic role by regulating its mRNA targets (e.g., MYB and Myc proto-oncogene protein (MYC)) through m6A modification, while the protein itself is negatively regulated by SPI1.

NAD-dependent protein deacetylase sirtuin-1 (SIRT1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL14*
Cell Line	HepG2 cell line	Homo sapiens
Treatment: shMETTL14 HepG2 cells Control: shCtrl HepG2 cells		GSE121949
Regulation		logFC: -7.26E-01 p-value: 1.60E-02
More Results	Click to View More RNA-seq Results

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			[37]
Responsed Disease	Chronic kidney disease [ICD-11: GB61.Z]
Responsed Drug	Doxil	Approved	Drug Info
Target Regulation	Down regulation
Cell Process	Cell apoptosis
In-vitro Model	Conditionally immortalized human podocytes (Podocytes)
In-vivo Model	To establish mice model with ADR nephropathy, adult male C57BL/6J mice (8-12 weeks of age) were purchased from Animal Center of Fudan University and injected with 19.5 mg/kg ADR (D1515, Sigma-Aldrich, St-Louis, MO, USA) intravenously via tail vein.
Response Summary	The elevated m6A RNA levels and the most upregulated METTL14 expression in kidneys of mice with adriamycin and diabetic nephropathy. METTL14-dependent RNA m6A modification contributes to podocyte injury through posttranscriptional regulation of NAD-dependent protein deacetylase sirtuin-1 (SIRT1) mRNA, which provide a potential approach for the diagnosis and treatment of podocytopathies.

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		[80]
Responsed Disease	Osteoporosis [ICD-11: FB83.1]
Target Regulation	Up regulation

Neurogenic differentiation factor 1 (NEUROD1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL14*
Cell Line	Embryonic stem cells	Mus musculus
Treatment: METTL14 knockout mESCs Control: Wild type mESCs		GSE156481
Regulation		logFC: -2.82E+00 p-value: 1.42E-13
More Results	Click to View More RNA-seq Results

Disorders of the retina [ICD-11: 9B70-9C0Z]

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	Disorders of the retina [ICD-11: 9B70-9C0Z]
Target Regulation	Down regulation
In-vitro Model	ARPE-19	Normal	Homo sapiens	CVCL_0145
Response Summary	The expression of METTL14 is significantly reduced in patients with retinitis pigmentosa (RP). METTL14 regulates the expression of MAP2 via the modification of m6A, resulting in the dysregulation of Neurogenic differentiation factor 1 (NEUROD1) and pathologic changes in RPE cells.

Neurogenic locus notch homolog protein 1 (NOTCH1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL14*
Cell Line	MDA-MB-231	Homo sapiens
Treatment: siMETTL14 MDA-MB-231 cells Control: MDA-MB-231 cells		GSE81164
Regulation		logFC: -8.37E-01 p-value: 6.43E-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		[38]
Responsed Disease	Bladder cancer [ICD-11: 2C94]
Target Regulation	Down regulation
Cell Process	Cell proliferation
	Self-renewal
	Cell metastasis
In-vitro Model	Primary bladder cancer cells (Obtained from bladder cancer patients)
Response Summary	Mettl14 and m6A modification participate in the RNA stability of Neurogenic locus notch homolog protein 1 (NOTCH1) mRNA. Notch1 plays an essential role in bladder tumorigenesis and bladder TIC self-renewal.

NF-kappa-B inhibitor alpha (Nfkbia)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL14*
Cell Line	mouse embryonic stem cells	Mus musculus
Treatment: METTL14-/- ESCs Control: Wild type ESCs		GSE145309
Regulation		logFC: 1.05E+00 p-value: 4.32E-28
More Results	Click to View More RNA-seq Results

Inflammatory bowel disease [ICD-11: DD7Z]

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	Inflammatory bowel disease [ICD-11: DD7Z]
Target Regulation	Down regulation
Pathway Response	NF-kappa B signaling pathway	hsa04064
Cell Process	Cell apoptosis
In-vivo Model	Mettl14^f/f mice were generated as previously described with CRISPR-Cas9 technology by insertion of two loxp sites into Mettl14 genome loci. Mettl14^f/f mice without Villin-Cre were used as WT controls (Mettl14 WT) for Mettl14 KO mice. Mettl14^f/f mice were crossed with Lgr5-eGFP-IRES-creERT2 (Lgr5-Cre) mice to generate Mettl14 depletion in Lgr⁵⁺ stem cells.
Response Summary	Colonic mucosal barrier dysfunction is one of the major causes of inflammatory bowel disease (IBD). Mettl14 restricted colonic epithelial cell death by regulating the stability of NF-kappa-B inhibitor alpha (Nfkbia) mRNA and modulating the NF-Kappa-B pathway,suggesting that m6A modification could be a potential therapeutic target for IBD.

Nucleosome-remodeling factor subunit BPTF (BPTF)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL14*
Cell Line	mouse embryonic stem cells	Mus musculus
Treatment: METTL14-/- ESCs Control: Wild type ESCs		GSE145309
Regulation		logFC: 9.11E-01 p-value: 2.73E-20
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				[40]
Responsed Disease	Renal cell carcinoma [ICD-11: 2C90]
Target Regulation	Down regulation
Pathway Response	Glycerolipid metabolism			hsa00561
Cell Process	Glycolysis
In-vitro Model	RenCa	Mouse kidney carcinoma	Mus musculus	CVCL_2174
	Caki-1	Clear cell renal cell carcinoma	Homo sapiens	CVCL_0234
	ACHN	Papillary renal cell carcinoma	Homo sapiens	CVCL_1067
	786-O	Renal cell carcinoma	Homo sapiens	CVCL_1051
In-vivo Model	To generate a highly metastatic orthotopic xenograft model, 1 × 10⁵ luciferase-expressing Renca cells (Luc-Renca) in 25 ul of 2:1 (v/v) PBS:Matrigel were injected into the right sub-renal capsule of the kidney of BALB/c mice (4 mice/group).
Response Summary	METTL14 deficiency promoted RCC metastasis in vitro and in vivo. Mechanistically, METTL14-mediated m6A modification negatively regulated the mRNA stability of Nucleosome-remodeling factor subunit BPTF (BPTF) and depended on BPTF to drive lung metastasis.

p53 apoptosis effector related to PMP-22 (PERP)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL14*
Cell Line	mouse embryonic stem cells	Mus musculus
Treatment: METTL14-/- ESCs Control: Wild type ESCs		GSE145309
Regulation		logFC: 1.56E+00 p-value: 2.67E-25
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				[41]
Responsed Disease	Pancreatic cancer [ICD-11: 2C10]
Target Regulation	Down regulation
In-vitro Model	SW1990	Pancreatic adenocarcinoma	Homo sapiens	CVCL_1723
	PANC-1	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0480
	Panc 03.27	Pancreatic adenocarcinoma	Homo sapiens	CVCL_1635
	MIA PaCa-2	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0428
	Capan-2	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0026
	BxPC-3	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0186
	AsPC-1	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0152
In-vivo Model	For the subcutaneous transplantation model, 100 uL of 1 × 10⁶ cells were injected subcutaneously into the right armpit of BALB/c nude mice. Animal weight and tumor diameter were measured once a week from the time of implantation.For the pancreatic cancer orthotopic implantation model, 200 uL of Panc02-lucifer cells (2 × 10⁷) were injected into the pancreas in mice anesthetized and laparotomized. After 4 weeks, the mice were anesthetized and injected with 150 mg/kg d-luciferin, via the tail vein.For the liver metastasis model, BALB/c nude mice received 2 × 10⁶ cells (in 100 uL DMEM), directly injected into the spleen. Their body weight was measured once a week from the time of implantation.
Response Summary	The upregulation of METTL14 leads to the decrease of p53 apoptosis effector related to PMP-22 (PERP) levels via m6A modification, promoting the growth and metastasis of pancreatic cancer; therefore METTL14 is a potential therapeutic target for its treatment.

PHLPP-like (PHLPP2)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL14*
Cell Line	MDA-MB-231	Homo sapiens
Treatment: siMETTL14 MDA-MB-231 cells Control: MDA-MB-231 cells		GSE81164
Regulation		logFC: 9.41E-01 p-value: 4.99E-14
More Results	Click to View More RNA-seq Results

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				[42]
Responsed Disease	Endometrial cancer [ICD-11: 2C76]
Target Regulation	Up regulation
Pathway Response	PI3K-Akt signaling pathway			hsa04151
Cell Process	Cell proliferation and tumorigenicity
In-vitro Model	HEC-1-A	Endometrial adenocarcinoma	Homo sapiens	CVCL_0293
	RL95-2	Endometrial adenosquamous carcinoma	Homo sapiens	CVCL_0505
	T HESCs	Normal	Homo sapiens	CVCL_C464
In-vivo Model	4×10⁶ HEC-1-A endometrial cancer cells (shCtrl, shMETTL3, wild-type, METTL14^+/-, or METTL14^+/- rescued with wild-type or mutant METTL14) were injected intraperitoneally into 5 week old female athymic nude mice (Foxn1^nu, Harlan; n=10 per group).
Response Summary	About 70% of endometrial tumours exhibit reductions in m6A methylation that are probably due to either this METTL14 mutation or reduced expression of METTL3. Reductions in m6A methylation lead to decreased expression of the negative AKT regulator PHLPP-like (PHLPP2) and increased expression of the positive AKT regulator mTORC2. these results reveal reduced m6A mRNA methylation as an oncogenic mechanism in endometrial cancer and identify m6A methylation as a regulator of AKT signalling.

PI3-kinase subunit alpha (PI3k/PIK3CA)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL14*
Cell Line	HepG2 cell line	Homo sapiens
Treatment: shMETTL14 HepG2 cells Control: shCtrl HepG2 cells		GSE121949
Regulation		logFC: -6.28E-01 p-value: 7.56E-03
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				[43]
Responsed Disease	Gastric cancer [ICD-11: 2B72]
Target Regulation	Down regulation
Pathway Response	PI3K-Akt signaling pathway			hsa04151
Pathway Response	mTOR signaling pathway			hsa04150
In-vitro Model	SGC-7901	Gastric carcinoma	Homo sapiens	CVCL_0520
	MGC-803	Gastric mucinous adenocarcinoma	Homo sapiens	CVCL_5334
	GES-1	Normal	Homo sapiens	CVCL_EQ22
Response Summary	The m6A modification level was decreased in GC and METTL14 was a key regulator resulting in m6A disorder in GC. METTL14 overexpression suppressed GC cell proliferation and aggression by deactivating the PI3-kinase subunit alpha (PI3k/PIK3CA)/AKT/mTOR pathway and the EMT pathway, respectively.

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				[20]
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulation	Down regulation
Pathway Response	PI3K-Akt signaling pathway			hsa04151
Cell Process	Epithelial-mesenchymal transition
In-vitro Model	YY-8103	Adult hepatocellular carcinoma	Homo sapiens	CVCL_WY40
	SMMC-7721	Endocervical adenocarcinoma	Homo sapiens	CVCL_0534
	HCCLM3	Adult hepatocellular carcinoma	Homo sapiens	CVCL_6832
	L-02	Endocervical adenocarcinoma	Homo sapiens	CVCL_6926
	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
	Hep 3B2.1-7	Childhood hepatocellular carcinoma	Homo sapiens	CVCL_0326
In-vivo Model	For the lung metastasis model, stably transfected HepG2 cells (1 × 10⁶/0.1 mL DMEM) were injected into each nude mouse through the tail vein. Five weeks later, mice were euthanized, and the lung tissues were collected.
Response Summary	METTL14 was found to inhibit HCC cell migration, invasion, and EMT through modulating EGFR/PI3-kinase subunit alpha (PI3k/PIK3CA)/AKT signaling pathway in an m6A-dependent manner.

PI3-kinase subunit beta (PIK3CB)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL14*
Cell Line	MDA-MB-231	Homo sapiens
Treatment: siMETTL14 MDA-MB-231 cells Control: MDA-MB-231 cells		GSE81164
Regulation		logFC: 5.88E-01 p-value: 1.08E-05
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				[44]
Responsed Disease	Pancreatic cancer [ICD-11: 2C10]
Responsed Drug	AZD6482		Terminated	Drug Info
Target Regulation	Up regulation
Pathway Response	PI3K-Akt signaling pathway			hsa04151
	Glycolysis / Gluconeogenesis			hsa00010
Cell Process	Glucose metabolism
In-vitro Model	BxPC-3	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0186
	PANC-1	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0480
In-vivo Model	Established cohorts of mice bearing tumour xenografts driven by PTEN-deficient BxPC-3 and PANC-1 cells with PIK3CB overexpression. When tumours grew to ~300 mm³, mice were grouped and administered with vehicle (DMSO) or KIN-193 via intraperitoneal injection (20 mg/kg) once daily.
Response Summary	N6-methyladenosine mRNA methylation of PIK3CB regulates AKT signalling to promote PTEN-deficient pancreatic cancer progression. Rs142933486 is significantly associated with the overall survival of PDAC by reducing the PIK3CB m6A level, which facilitated its mRNA and protein expression levels mediated by the m6A 'writer' complex (METTL13/METTL14/WTAP) and the m6A 'reader' YTHDF2. KIN-193, a PI3-kinase subunit beta (PIK3CB)-selective inhibitor, is shown to serve as an effective anticancer agent for blocking PTEN-deficient PDAC.

Proline-rich AKT1 substrate 1 (AKT1S1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL14*
Cell Line	mouse embryonic stem cells	Mus musculus
Treatment: METTL14-/- ESCs Control: Wild type ESCs		GSE145309
Regulation		logFC: 6.65E-01 p-value: 2.87E-13
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				[45]
Responsed Disease	Gastric cancer [ICD-11: 2B72]
Target Regulation	Down regulation
In-vitro Model	SGC-7901	Gastric carcinoma	Homo sapiens	CVCL_0520
	MKN28	Gastric tubular adenocarcinoma	Homo sapiens	CVCL_1416
	MGC-803	Gastric mucinous adenocarcinoma	Homo sapiens	CVCL_5334
	GES-1	Normal	Homo sapiens	CVCL_EQ22
	BGC-823	Gastric carcinoma	Homo sapiens	CVCL_3360
	AGS	Gastric adenocarcinoma	Homo sapiens	CVCL_0139
Response Summary	METTL14-mediated m6A modification of circORC5 suppresses gastric cancer progression by regulating miR-30c-2-3p/Proline-rich AKT1 substrate 1 (AKT1S1) axis. METTL14 was downregulated in GC tissue samples and its low expression acted as a prognostic factor of poor survival in patients with GC.

Protein phosphatase 1A (PPM1A)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL14*
Cell Line	Neural progenitor cell line	Mus musculus
Treatment: METTL14 knockout NPCs Control: Wild type NPCs		GSE158985
Regulation		logFC: 6.97E-01 p-value: 2.44E-03
More Results	Click to View More RNA-seq Results

Male infertility [ICD-11: GB04]

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	Azoospermia [ICD-11: GB04.0]
Target Regulation	Up regulation
Pathway Response	Autophagy			hsa04140
Cell Process	RNA stability
	Cell autophagy
In-vitro Model	TM3	Normal	Mus musculus	CVCL_4326
In-vivo Model	Male SPF BALB/c mice (qls02-0202) were purchased from Qinglongshan animal breeding farm. Mice were sacrificed by CO₂ asphyxiation and testes were obtained for following histopathological analyses.
Response Summary	m6A modification promoted translation of Protein phosphatase 1A (PPM1A) (protein phosphatase 1A, magnesium dependent, alpha isoform), a negative AMP-activated protein kinase (AMPK) regulator, but decreased expression of CAMKK2 (calcium/calmodulin-dependent protein kinase kinase 2, beta), a positive AMPK regulator, by reducing its RNA stability. Similar regulation of METTL14, ALKBH5, and m6A was also observed in LCs upon treatment with human chorionic gonadotropin (HsCG). Knock down of YTHDF1 failed to change the expression of CAMKK2 Providing insight into novel therapeutic strategies by exploiting m6A RNA methylation as targets for treating azoospermatism and oligospermatism patients with reduction in serum testosterone.

Putative C->U-editing enzyme APOBEC-4 (APOBEC4)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL14*
Cell Line	CT26 cell line	Mus musculus
Treatment: METTL14 knockout CT26 cells Control: CT26 cells		GSE142589
Regulation		logFC: 1.15E+00 p-value: 4.95E-02
More Results	Click to View More RNA-seq Results

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				[46]
Responsed Disease	Ovarian cancer [ICD-11: 2C73]
In-vitro Model	HEY	Ovarian serous adenocarcinoma	Homo sapiens	CVCL_0297
In-vitro Model	THP-1	Childhood acute monocytic leukemia	Homo sapiens	CVCL_0006
Response Summary	Putative C->U-editing enzyme APOBEC-4 (APOBEC4) was found to be significantly correlated with m6A regulators such as WTAP, METTL14, ZC3H13, RBM15B, and FMR1. APOBEC3A was identified as a protective factor from comprehensive analyses based on the immune microenvironment and genomic instability of ovarian cancer. APOBEC3A had the potential to serve as a promising prognostic biomarker for foretelling the survival and immunotherapy response of ovarian cancer patients.

RAC-alpha serine/threonine-protein kinase (AKT1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL14*
Cell Line	Neural progenitor cell line	Mus musculus
Treatment: METTL14 knockout NPCs Control: Wild type NPCs		GSE158985
Regulation		logFC: 8.08E-01 p-value: 3.19E-03
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				[43]
Responsed Disease	Gastric cancer [ICD-11: 2B72]
Target Regulation	Down regulation
Pathway Response	PI3K-Akt signaling pathway			hsa04151
Pathway Response	mTOR signaling pathway			hsa04150
In-vitro Model	SGC-7901	Gastric carcinoma	Homo sapiens	CVCL_0520
	MGC-803	Gastric mucinous adenocarcinoma	Homo sapiens	CVCL_5334
	GES-1	Normal	Homo sapiens	CVCL_EQ22
Response Summary	The m6A modification level was decreased in GC and METTL14 was a key regulator resulting in m6A disorder in GC. METTL14 overexpression suppressed GC cell proliferation and aggression by deactivating the PI3K/RAC-alpha serine/threonine-protein kinase (AKT1)/mTOR pathway and the EMT pathway, respectively.

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				[20]
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulation	Down regulation
Pathway Response	PI3K-Akt signaling pathway			hsa04151
Cell Process	Epithelial-mesenchymal transition
In-vitro Model	YY-8103	Adult hepatocellular carcinoma	Homo sapiens	CVCL_WY40
	SMMC-7721	Endocervical adenocarcinoma	Homo sapiens	CVCL_0534
	HCCLM3	Adult hepatocellular carcinoma	Homo sapiens	CVCL_6832
	L-02	Endocervical adenocarcinoma	Homo sapiens	CVCL_6926
	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
	Hep 3B2.1-7	Childhood hepatocellular carcinoma	Homo sapiens	CVCL_0326
In-vivo Model	For the lung metastasis model, stably transfected HepG2 cells (1 × 10⁶/0.1 mL DMEM) were injected into each nude mouse through the tail vein. Five weeks later, mice were euthanized, and the lung tissues were collected.
Response Summary	METTL14 was found to inhibit HCC cell migration, invasion, and EMT through modulating EGFR/PI3K/RAC-alpha serine/threonine-protein kinase (AKT1) signaling pathway in an m6A-dependent manner.

RIG-I-like receptor 1 (RIG-I)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL14*
Cell Line	Embryonic stem cells	Mus musculus
Treatment: METTL14 knockout mESCs Control: Wild type mESCs		GSE156481
Regulation		logFC: -1.26E+00 p-value: 3.52E-15
More Results	Click to View More RNA-seq Results

Acute viral hepatitis [ICD-11: 1E50]

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	Acute hepatitis B [ICD-11: 1E50.1]
Target Regulation	Down regulation
Pathway Response	RIG-I-like receptor signaling pathway			hsa04622
In-vitro Model	Huh-7	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0336
In-vitro Model	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
Response Summary	METTL3 and METTL14 leads to an increase in viral RNA recognition by RIG-I-like receptor 1 (RIG-I), thereby stimulating type I interferon production. The obvious advantage is that m6A deficiency in HBV and HCV induces a higher IFN synthesis and in turn enhance adaptive immunity.

Solute carrier family 40 member 1 (FPN1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL14*
Cell Line	HepG2 cell line	Homo sapiens
Treatment: shMETTL14 HepG2 cells Control: shCtrl HepG2 cells		GSE121949
Regulation		logFC: 1.09E+00 p-value: 8.51E-14
More Results	Click to View More RNA-seq Results

Breast cancer [ICD-11: 2C60]

In total 3 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[8]
Responsed Disease	Breast cancer [ICD-11: 2C60]
Responsed Drug	Pertuzumab		Approved	Drug Info
Target Regulation	Down regulation
Pathway Response	Wnt signaling pathway			hsa04310
Cell Process	Glutathione synthesis
In-vitro Model	ZR-75-1	Invasive breast carcinoma	Homo sapiens	CVCL_0588
	T-47D	Invasive breast carcinoma	Homo sapiens	CVCL_0553
	SUM-159 (A mesenchymal triple-negative breast cancer cell line)
	SK-BR-3	Breast adenocarcinoma	Homo sapiens	CVCL_0033
	MDA-MB-468	Breast adenocarcinoma	Homo sapiens	CVCL_0419
	MDA-MB-453	Breast adenocarcinoma	Homo sapiens	CVCL_0418
	MDA-MB-361	Breast adenocarcinoma	Homo sapiens	CVCL_0620
	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
	HEK293T	Normal	Homo sapiens	CVCL_0063
	BT-549	Invasive breast carcinoma	Homo sapiens	CVCL_1092
	BT-474	Invasive breast carcinoma	Homo sapiens	CVCL_0179
	AU565	Breast adenocarcinoma	Homo sapiens	CVCL_1074
In-vivo Model	Luciferase-labeled rSKBR3 and MDA-MB-361 cells (1 × 10⁷ cells) mixed with 1:1 Matrigel (Corning, 356237) were subcutaneously injected into the fat pads of mice. After a tumor was palpable, the mice were randomized into four groups (five mice per group), and they were treated with vehicle, trastuzumab (20 mg/kg, intraperitoneal administration), roblitinib (30 mg/kg, oral administration), or a combination of both drugs.
Response Summary	m6A-hypomethylation regulated FGFR4 phosphorylates GSK-3beta and activates beta-catenin/TCF4-SLC7A11/Solute carrier family 40 member 1 (FPN1) signaling to drive anti-HER2 resistance. Knockdown of METTL14 significantly increased the expression level of FGFR4 in HER2-positive breast cancer cells. FGFR4 reduced the sensitivity of HER2-positive breast cancer to trastuzumab plus pertuzumab or tucatinib. These results pinpoint a mechanism of anti-HER2 resistance and provide a strategy for overcoming resistance via FGFR4 inhibition in recalcitrant HER2-positive breast cancer.
Experiment 2 Reporting the m6A-centered Disease Response of This Target Gene				[8]
Responsed Disease	Breast cancer [ICD-11: 2C60]
Responsed Drug	Trastuzumab		Approved	Drug Info
Target Regulation	Down regulation
Pathway Response	Wnt signaling pathway			hsa04310
Cell Process	Glutathione synthesis
In-vitro Model	ZR-75-1	Invasive breast carcinoma	Homo sapiens	CVCL_0588
	T-47D	Invasive breast carcinoma	Homo sapiens	CVCL_0553
	SUM-159 (A mesenchymal triple-negative breast cancer cell line)
	SK-BR-3	Breast adenocarcinoma	Homo sapiens	CVCL_0033
	MDA-MB-468	Breast adenocarcinoma	Homo sapiens	CVCL_0419
	MDA-MB-453	Breast adenocarcinoma	Homo sapiens	CVCL_0418
	MDA-MB-361	Breast adenocarcinoma	Homo sapiens	CVCL_0620
	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
	HEK293T	Normal	Homo sapiens	CVCL_0063
	BT-549	Invasive breast carcinoma	Homo sapiens	CVCL_1092
	BT-474	Invasive breast carcinoma	Homo sapiens	CVCL_0179
	AU565	Breast adenocarcinoma	Homo sapiens	CVCL_1074
In-vivo Model	Luciferase-labeled rSKBR3 and MDA-MB-361 cells (1 × 10⁷ cells) mixed with 1:1 Matrigel (Corning, 356237) were subcutaneously injected into the fat pads of mice. After a tumor was palpable, the mice were randomized into four groups (five mice per group), and they were treated with vehicle, trastuzumab (20 mg/kg, intraperitoneal administration), roblitinib (30 mg/kg, oral administration), or a combination of both drugs.
Response Summary	m6A-hypomethylation regulated FGFR4 phosphorylates GSK-3beta and activates beta-catenin/TCF4-SLC7A11/Solute carrier family 40 member 1 (FPN1) signaling to drive anti-HER2 resistance. Knockdown of METTL14 significantly increased the expression level of FGFR4 in HER2-positive breast cancer cells. FGFR4 reduced the sensitivity of HER2-positive breast cancer to trastuzumab plus pertuzumab or tucatinib. These results pinpoint a mechanism of anti-HER2 resistance and provide a strategy for overcoming resistance via FGFR4 inhibition in recalcitrant HER2-positive breast cancer.
Experiment 3 Reporting the m6A-centered Disease Response of This Target Gene				[8]
Responsed Disease	Breast cancer [ICD-11: 2C60]
Responsed Drug	Tucatinib		Approved	Drug Info
Target Regulation	Down regulation
Pathway Response	Wnt signaling pathway			hsa04310
Cell Process	Glutathione synthesis
In-vitro Model	ZR-75-1	Invasive breast carcinoma	Homo sapiens	CVCL_0588
	T-47D	Invasive breast carcinoma	Homo sapiens	CVCL_0553
	SUM-159 (A mesenchymal triple-negative breast cancer cell line)
	SK-BR-3	Breast adenocarcinoma	Homo sapiens	CVCL_0033
	MDA-MB-468	Breast adenocarcinoma	Homo sapiens	CVCL_0419
	MDA-MB-453	Breast adenocarcinoma	Homo sapiens	CVCL_0418
	MDA-MB-361	Breast adenocarcinoma	Homo sapiens	CVCL_0620
	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
	HEK293T	Normal	Homo sapiens	CVCL_0063
	BT-549	Invasive breast carcinoma	Homo sapiens	CVCL_1092
	BT-474	Invasive breast carcinoma	Homo sapiens	CVCL_0179
	AU565	Breast adenocarcinoma	Homo sapiens	CVCL_1074
In-vivo Model	Luciferase-labeled rSKBR3 and MDA-MB-361 cells (1 × 10⁷ cells) mixed with 1:1 Matrigel (Corning, 356237) were subcutaneously injected into the fat pads of mice. After a tumor was palpable, the mice were randomized into four groups (five mice per group), and they were treated with vehicle, trastuzumab (20 mg/kg, intraperitoneal administration), roblitinib (30 mg/kg, oral administration), or a combination of both drugs.
Response Summary	m6A-hypomethylation regulated FGFR4 phosphorylates GSK-3beta and activates beta-catenin/TCF4-SLC7A11/Solute carrier family 40 member 1 (FPN1) signaling to drive anti-HER2 resistance. Knockdown of METTL14 significantly increased the expression level of FGFR4 in HER2-positive breast cancer cells. FGFR4 reduced the sensitivity of HER2-positive breast cancer to trastuzumab plus pertuzumab or tucatinib. These results pinpoint a mechanism of anti-HER2 resistance and provide a strategy for overcoming resistance via FGFR4 inhibition in recalcitrant HER2-positive breast cancer.

Stearoyl-CoA desaturase (SCD)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL14*
Cell Line	HepG2 cell line	Homo sapiens
Treatment: shMETTL14 HepG2 cells Control: shCtrl HepG2 cells		GSE121949
Regulation		logFC: 1.25E+00 p-value: 7.56E-25
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				[3]
Responsed Disease	Non-alcoholic fatty liver disease [ICD-11: DB92]
Target Regulation	Up regulation
Pathway Response	Glycerolipid metabolism			hsa00561
Cell Process	Lipid metabolism
In-vitro Model	LM3	Malignant neoplasms	Mus musculus	CVCL_D269
In-vitro Model	MHCC97-H	Adult hepatocellular carcinoma	Homo sapiens	CVCL_4972
In-vivo Model	Mice with a Tmem30a deletion specifically in pancreatic beta cells were generated as previously described. Mice developed with NAFLD were named for Tmem30a-associated NAFLD (TAN) mice. The littermate mice with genotypes of Tmem30a^loxP/loxP were used as controls.
Response Summary	Targeting METTL3/14 in vitro increases protein level of ACLY and Stearoyl-CoA desaturase (SCD) as well as triglyceride and cholesterol production and accumulation of lipid droplets. These findings demonstrate a new NAFLD mouse model that provides a study platform for DM2-related NAFLD and reveals a unique epitranscriptional regulating mechanism for lipid metabolism via m6A-modified protein expression of ACLY and SCD1.

Colon cancer [ICD-11: 2B90]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[91]
Responsed Disease	Colon cancer [ICD-11: 2B90]
Target Regulation	Down regulation
Pathway Response	Wnt signaling pathway			hsa04310
In-vitro Model	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
In-vitro Model	SW620	Colon adenocarcinoma	Homo sapiens	CVCL_0547

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]
In-vitro Model	HeLa	Endocervical adenocarcinoma	Homo sapiens	CVCL_0030
In-vitro Model	SiHa	Cervical squamous cell carcinoma	Homo sapiens	CVCL_0032

Tastin (TROAP)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL14*
Cell Line	IL7H6 cell line	Mus musculus
Treatment: METTL14 knockout IL7H6 cells Control: Wild type IL7H6 cells		GSE151071
Regulation		logFC: -1.07E+00 p-value: 3.99E-03
More Results	Click to View More RNA-seq Results

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				[48]
Responsed Disease	Ovarian cancer [ICD-11: 2C73]
Target Regulation	Down regulation
In-vitro Model	SK-OV-3	Ovarian serous cystadenocarcinoma	Homo sapiens	CVCL_0532
In-vitro Model	A2780	Ovarian endometrioid adenocarcinoma	Homo sapiens	CVCL_0134
In-vivo Model	KOV-3 cells (1 ×10⁶) stable transfected with METTL14 or control lentivirus, were injected subcutaneously into the right flank of BALB/c nude mice.
Response Summary	METTL14 overexpression decreased ovarian cancer proliferation by inhibition of Tastin (TROAP) expression via an m6A RNA methylation-dependent mechanism.

Thrombospondin-1 (THBS1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL14*
Cell Line	HepG2 cell line	Homo sapiens
Treatment: shMETTL14 HepG2 cells Control: shCtrl HepG2 cells		GSE121949
Regulation		logFC: -1.33E+00 p-value: 7.54E-27
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				[49]
Responsed Disease	Prostate cancer [ICD-11: 2C82]
Target Regulation	Down regulation
Pathway Response	RNA degradation			hsa03018
Cell Process	Cell proliferation
In-vitro Model	PC-3	Prostate carcinoma	Homo sapiens	CVCL_0035
In-vitro Model	DU145	Prostate carcinoma	Homo sapiens	CVCL_0105
In-vivo Model	Stably transfected shMETTL14 and shNC DU145 cells (5×10⁶ cells) suspended in a mixture of 100uL PBS were subcutaneously injected into the right flank of male nude BALB/C mice (6-8 weeks old) to induce tumor formation.
Response Summary	In prostate cancer, METTL14 downregulated Thrombospondin-1 (THBS1) expression in an m6A-dependent manner, which resulted in the recruitment of YTHDF2 to recognize and degrade Thrombospondin 1 (THBS1) mRNA.

TNF receptor-associated factor 1 (TRAF1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL14*
Cell Line	MDA-MB-231	Homo sapiens
Treatment: siMETTL14 MDA-MB-231 cells Control: MDA-MB-231 cells		GSE81164
Regulation		logFC: -8.04E-01 p-value: 5.72E-05
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				[50]
Responsed Disease	Renal cell carcinoma [ICD-11: 2C90]
Responsed Drug	Sunitinib		Approved	Drug Info
Target Regulation	Up regulation
Cell Process	RNA stability
Cell Process	Cell apoptosis
In-vitro Model	OS-RC-2	Clear cell renal cell carcinoma	Homo sapiens	CVCL_1626
	HUVEC-C	Normal	Homo sapiens	CVCL_2959
	786-O	Renal cell carcinoma	Homo sapiens	CVCL_1051
In-vivo Model	For the xenograft tumor model, approximately 1 × 10⁶ ccRCC cells suspended in 100 uL PBS were subcutaneously inoculated in the right flank of 5-week-old BALB/c nude mice. For the ccRCC orthotopic implantation model, approximately 1 × 10⁶ ccRCC cells suspended in 30 uL Matrigel were injected under the renal capsule of 5-week-old BALB/c nude mice. After 6 weeks, the anesthetized mice were intraperitoneally injected with D-luciferin (Yeason) and imaged using an in vivo imaging system to detect tumor growth and metastasis. For the lung metastasis model, approximately 5 × 10⁵ ccRCC cells suspended in PBS were injected into the tail vein of 5-week-old mice. After 6-8 weeks, mice were anesthetized and lung metastasis was imaged as above.
Response Summary	In renal cell carcinoma, overexpression of TNF receptor-associated factor 1 (TRAF1) promotes sunitinib resistance by modulating apoptotic and angiogenic pathways in a METTL14-dependent manner.

Transcription factor E2F8 (E2F8)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL14*
Cell Line	MDA-MB-231	Homo sapiens
Treatment: siMETTL14 MDA-MB-231 cells Control: MDA-MB-231 cells		GSE81164
Regulation		logFC: -6.53E-01 p-value: 4.62E-05
More Results	Click to View More RNA-seq Results

Breast cancer [ICD-11: 2C60]

In total 3 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[51]
Responsed Disease	Breast cancer [ICD-11: 2C60]
Responsed Drug	Cisplatin		Approved	Drug Info
Target Regulation	Up regulation
Pathway Response	Nucleotide excision repair			hsa03420
Cell Process	RNA stability
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
In-vivo Model	1×10⁶ MDA-MB-231 cells were resuspended in 100 uL PBS with 50% Matrigel (Corning Costar, USA), and injected into the mammary fat pad of the mice.
Response Summary	In breast cancer, accordingly YTHDF1 knockdown sensitizes breast cancer cells to Adriamycin and Cisplatin as well as Olaparib, a PARP inhibitor. Transcription factor E2F8 (E2F8) is a target molecule by YTHDF1 which modulates E2F8 mRNA stability and DNA damage repair in a METTL14-dependent manner.
Experiment 2 Reporting the m6A-centered Disease Response of This Target Gene				[51]
Responsed Disease	Breast cancer [ICD-11: 2C60]
Responsed Drug	Doxil		Approved	Drug Info
Target Regulation	Up regulation
Pathway Response	Nucleotide excision repair			hsa03420
Cell Process	RNA stability
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
In-vivo Model	1×10⁶ MDA-MB-231 cells were resuspended in 100 uL PBS with 50% Matrigel (Corning Costar, USA), and injected into the mammary fat pad of the mice.
Response Summary	In breast cancer, accordingly YTHDF1 knockdown sensitizes breast cancer cells to Adriamycin and Cisplatin as well as Olaparib, a PARP inhibitor. Transcription factor E2F8 (E2F8) is a target molecule by YTHDF1 which modulates E2F8 mRNA stability and DNA damage repair in a METTL14-dependent manner.
Experiment 3 Reporting the m6A-centered Disease Response of This Target Gene				[51]
Responsed Disease	Breast cancer [ICD-11: 2C60]
Responsed Drug	Olaparib		Approved	Drug Info
Target Regulation	Up regulation
Pathway Response	Nucleotide excision repair			hsa03420
Cell Process	RNA stability
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
In-vivo Model	1×10⁶ MDA-MB-231 cells were resuspended in 100 uL PBS with 50% Matrigel (Corning Costar, USA), and injected into the mammary fat pad of the mice.
Response Summary	In breast cancer, accordingly YTHDF1 knockdown sensitizes breast cancer cells to Adriamycin and Cisplatin as well as Olaparib, a PARP inhibitor. Transcription factor E2F8 (E2F8) is a target molecule by YTHDF1 which modulates E2F8 mRNA stability and DNA damage repair in a METTL14-dependent manner.

Transcription factor ISGF-3 components p91/p84 (Stat1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL14*
Cell Line	Embryonic stem cells	Mus musculus
Treatment: METTL14 knockout mESCs Control: Wild type mESCs		GSE156481
Regulation		logFC: -1.12E+00 p-value: 2.46E-07
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				[5]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulation	Down regulation
Pathway Response	PD-L1 expression and PD-1 checkpoint pathway in cancer			hsa05235
Cell Process	Immunity
In-vitro Model	CT26	Mouse colon adenocarcinoma	Mus musculus	CVCL_7254
	B16-GM-CSF (B16-GM-CSF cell line was a kind gift from Drs. Glenn Dranoff and Michael Dougan (Dana-Farber/Harvard Cancer Center))
	B16-F10	Mouse melanoma	Mus musculus	CVCL_0159
In-vivo Model	2 × 10⁶ CT26 cells with knockout of Mettl3, Mettl14, Mettl3/Stat1, Mettl3/Irf1, Mettl14/Stat1, or Mettl14/Irf1 and control were suspended in 200 uL of PBS/Matrigel (Corning) (1:1) and then subcutaneously inoculated into flank of each mouse.
Response Summary	In colorectal cancer, Mettl3- or Mettl14-deficient tumors increased cytotoxic tumor-infiltrating CD8+ T cells and elevated secretion of IFN-gamma, Cxcl9, and Cxcl10 in tumor microenvironment in vivo. Mechanistically, Mettl3 or Mettl14 loss promoted IFN-gamma-Stat1-Irf1 signaling through stabilizing the Transcription factor ISGF-3 components p91/p84 (Stat1) and Irf1 mRNA via Ythdf2.

Transcription factor p65 (RELA)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL14*
Cell Line	BMDM	Mus musculus
Treatment: METTL14 knockout mice BMDM Control: Wild type mice BMDM		GSE153512
Regulation		logFC: 7.00E-01 p-value: 8.41E-10
More Results	Click to View More RNA-seq Results

Atherosclerosis [ICD-11: BD40]

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	Atherosclerosis [ICD-11: BD40.Z]
Target Regulation	Up regulation
Cell Process	Cell apoptosis
In-vitro Model	HUVEC-C	Normal	Homo sapiens	CVCL_2959
In-vitro Model	EA.hy 926	Normal	Homo sapiens	CVCL_3901
In-vivo Model	The mice were randomly divided into control, Ad-sh-NC, and Ad-sh-METTL14 groups (10 mice per group). The mice in the control group were fed a normal diet, while the Ad-sh-NC and Ad-sh-METTL14 groups were fed a high-fat diet (20% fat and 0.25% cholesterol). Furthermore, 300 uL of constructed sh-NC or sh-METTL14 adenovirus was injected every 3 weeks into the caudal veins of mice from the Ad-sh-NC or Ad-sh-METTL14 groups, respectively. The constructed vectors were obtained from HanBio Technology Co., Ltd. (Shanghai, China). All mice were sacrificed after 24 weeks and the aortas were separated for further experiments.
Response Summary	Knocking down METTL14 could inhibit the development of atherosclerosis in high-fat diet-treated APOE mice. After transfection with si-METTL14, the bcl-2 expression level and the viability of ox-LDL-incubated cells increased, whereas the apoptosis rate and the expressions of Bax and cleaved caspase-3 decreased. However, the effect of METTL14 knockdown was reversed by Transcription factor p65 (RELA) overexpression.

Transcription factor SOX-4 (SOX4)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL14*
Cell Line	HepG2 cell line	Homo sapiens
Treatment: shMETTL14 HepG2 cells Control: shCtrl HepG2 cells		GSE121949
Regulation		logFC: -2.04E+00 p-value: 4.12E-17
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				[52]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulation	Down regulation
Pathway Response	PI3K-Akt signaling pathway			hsa04151
Cell Process	Cell migration
	Cell invasion
	Cell metastasis
In-vitro Model	DLD-1	Colon adenocarcinoma	Homo sapiens	CVCL_0248
	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	HCT 8	Colon adenocarcinoma	Homo sapiens	CVCL_2478
	HT29	Colon cancer	Mus musculus	CVCL_A8EZ
	NCM460	Normal	Homo sapiens	CVCL_0460
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
	SW620	Colon adenocarcinoma	Homo sapiens	CVCL_0547
In-vivo Model	2 × 10⁶ transfected HCT116 cells in 0.2 ml PBS were injected into the tail vein of nude mice which were randomly divided into nine groups (eight mice per group).
Response Summary	METTL14 inhibited colorectal cancer malignant process partly through Transcription factor SOX-4 (SOX4)-mediated EMT process and PI3K/Akt signals.

Transcriptional activator Myb (MYB)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL14*
Cell Line	MDA-MB-231	Homo sapiens
Treatment: siMETTL14 MDA-MB-231 cells Control: MDA-MB-231 cells		GSE81164
Regulation		logFC: 9.21E-01 p-value: 4.44E-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				[36]
Responsed Disease	Acute myeloid leukaemia [ICD-11: 2A60]
Target Regulation	Up regulation
Cell Process	Cell survival/proliferation
In-vitro Model	HEK293T	Normal	Homo sapiens	CVCL_0063
	HSPC (Human hematopoietic stem cell)
	MNC (Cord blood pluripotent stem cells)
	OP9	Normal	Mus musculus	CVCL_4398
	U-937	Adult acute monocytic leukemia	Homo sapiens	CVCL_0007
In-vivo Model	Lin^- HSPCs were purified from BM of wildtype mice and 0.1×10⁶ cells were seeded in 2 mL OP9 medium onto the OP9 cells with the addition of 10 ng/mL mouse IL-3, 10 ng/mL human IL-6, 10 ng/mL mouse IL-7, 10 ng/mL mouse Flt-3L, and 50 ng/mL mouse stem cell factor (SCF).
Response Summary	METTL14 in normal myelopoiesis and AML pathogenesis, as featured by blocking myeloid differentiation and promoting self-renewal of normal HSPCs and LSCs/LICs. METTL14 exerts its oncogenic role by regulating its mRNA targets (e.g., Transcriptional activator Myb (MYB) and MYC) through m6A modification, while the protein itself is negatively regulated by SPI1.

Transcriptional coactivator YAP1 (YAP1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL14*
Cell Line	MDA-MB-231	Homo sapiens
Treatment: siMETTL14 MDA-MB-231 cells Control: MDA-MB-231 cells		GSE81164
Regulation		logFC: 1.32E+00 p-value: 8.59E-29
More Results	Click to View More RNA-seq Results

Urinary/pelvic organs injury [ICD-11: NB92]

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	Injury of kidney [ICD-11: NB92.0]
Target Regulation	Down regulation
Pathway Response	Hippo signaling pathway			hsa04390
Cell Process	Cell proliferation and metastasis
In-vitro Model	HK2	Normal	Acipenser baerii	CVCL_YE28
Response Summary	METTL14 promotes renal ischemic reperfusion injury via suppressing Transcriptional coactivator YAP1 (YAP1).

Triple-negative breast cancer [ICD-11: 2C6Z]

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	Triple-negative breast cancer [ICD-11: 2C6Z]
Target Regulation	Down regulation

Tribbles homolog 2 (TRIB2)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL14*
Cell Line	mouse embryonic stem cells	Mus musculus
Treatment: METTL14-/- ESCs Control: Wild type ESCs		GSE145309
Regulation		logFC: 3.83E+00 p-value: 1.54E-161
More Results	Click to View More RNA-seq Results

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				[54]
Responsed Disease	Esophageal squamous cell carcinoma [ICD-11: 2B70.1]
Target Regulation	Down regulation
Pathway Response	Ubiquitin mediated proteolysis			hsa04120
Cell Process	Proteasome pathway degradation
In-vitro Model	TE-1	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1759
	KYSE-410	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1352
	KYSE-150	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1348
	HET-1A	Normal	Homo sapiens	CVCL_3702
	HEK293T	Normal	Homo sapiens	CVCL_0063
	Eca-109	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_6898
	CVCL_E307	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_E307
In-vivo Model	Fresh PDX tumor samples collected from two established PDX models (PDX #07 with high TRIB2 expression and PDX #12 with low TRIB2, passages three to four) were minced and subcutaneously implanted into the flanks of 3- to 4-week-old female BALB/c nude mice (Jiesijie Laboratory Animals).
Response Summary	METTL14, an m6A RNA methyltransferase downregulated in ESCC, suppresses Tribbles homolog 2 (TRIB2) expression via miR-99a-5p-mediated degradation of TRIB2 mRNA by targeting its 3' untranslated region, whereas TRIB2 induces ubiquitin-mediated proteasomal degradation of METTL14 in a COP1-dependent manner.

Tumor necrosis factor (TNF/TNF-alpha)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL14*
Cell Line	CT26 cell line	Mus musculus
Treatment: METTL14 knockout CT26 cells Control: CT26 cells		GSE142589
Regulation		logFC: 1.47E+00 p-value: 1.57E-04
More Results	Click to View More RNA-seq Results

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		[55]
Responsed Disease	Chronic kidney disease [ICD-11: GB61.Z]
Target Regulation	Up regulation
Pathway Response	NF-kappa B signaling pathway	hsa04064
	AGE-RAGE signaling pathway in diabetic complications	hsa04933
	Apoptosis	hsa04210
Cell Process	Cell apoptosis
In-vitro Model	HRGECs cell line (Human glomerular microvascular endothelial cells)
In-vivo Model	After adaptive feeding for 1 week, db/db mice were randomly divided into five groups (n = 6): db/db group, db/db + rAAV group, db/db + rAAV-METTL14 group, db/db + rAAV-klotho group, and db/db + rAAV-METTL14 + rAAV-klotho group. Except db/db group, the other four groups were injected with recombinant adeno-associated virus (rAAV) control, rAAV mediated delivery of METTL14 (rAAV-METTL14), or/and rAAV mediated delivery of klotho (rAAV-klotho) respectively via tail vein. Six db/m mice were chosen as the normal control.
Response Summary	METTL14 could aggravated high glucose-induced glomerular endothelial cell injury and diabetic nephropathy through m6A modification of alpha-klotho. METTL14 silence decreased the levels of ROS, Tumor necrosis factor (TNF/TNF-alpha) and IL-6 and cell apoptosis.

Tyrosine-protein kinase receptor Tie-1 (TIE1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL14*
Cell Line	HepG2 cell line	Homo sapiens
Treatment: shMETTL14 HepG2 cells Control: shCtrl HepG2 cells		GSE121949
Regulation		logFC: -1.32E+00 p-value: 5.08E-05
More Results	Click to View More RNA-seq Results

Haemorrhoids [ICD-11: DB60]

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	Haemorrhoids [ICD-11: DB60]
Target Regulation	Up regulation
Pathway Response	VEGF signaling pathway			hsa04370
Cell Process	Cell proliferation
In-vitro Model	HUVEC-C	Normal	Homo sapiens	CVCL_2959
Response Summary	The overexpression of miR-4729 in vascular endothelial cells decreased the global mRNA methylation and TIE1 mRNA 3'UTR-specific site methylation by silencing METTL14 expression, reducing Tyrosine-protein kinase receptor Tie-1 (TIE1) mRNA stability, down-regulating the TIE1/VEGFA signal molecular loop expression, and weakening angiogenesis ability. MiR-4729 regulates TIE1 mRNA m6A modification and angiogenesis in hemorrhoids by targeting METTL14.

Tyrosine-protein phosphatase non-receptor type 6 (PTPN6)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL14*
Cell Line	IL7H6 cell line	Mus musculus
Treatment: METTL14 knockout IL7H6 cells Control: Wild type IL7H6 cells		GSE151071
Regulation		logFC: -1.44E+00 p-value: 2.37E-10
More Results	Click to View More RNA-seq Results

Osteonecrosis [ICD-11: FB81]

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	Osteonecrosis, unspecified [ICD-11: FB81.Z]
Target Regulation	Up regulation
Pathway Response	Wnt signaling pathway	hsa04310
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))
Response Summary	Imbalanced osteogenic/adipogenic differentiation of bone marrow mesenchymal stem cells BMSCs is considered the core pathological characteristic of SONFH. METTL14 regulated Tyrosine-protein phosphatase non-receptor type 6 (PTPN6) expression by increasing PTPN6 mRNA stability in an m6A-dependent manner. Moreover, PTPN6 knockdown abrogated the beneficial effects of METTL14 overexpression on BMSCs.

Ubiquitin carboxyl-terminal hydrolase 48 (USP48)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL14*
Cell Line	mouse embryonic stem cells	Mus musculus
Treatment: METTL14-/- ESCs Control: Wild type ESCs		GSE145309
Regulation		logFC: -5.96E-01 p-value: 3.62E-16
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				[58]
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulation	Up regulation
Pathway Response	Ubiquitin mediated proteolysis			hsa04120
	Glycolysis / Gluconeogenesis			hsa00010
Cell Process	Ubiquitination degradation
	Glycolysis
In-vitro Model	BEL-7404	Endocervical adenocarcinoma	Homo sapiens	CVCL_6568
	Huh-7	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0336
	SK-HEP-1	Liver and intrahepatic bile duct epithelial neoplasm	Homo sapiens	CVCL_0525
	SK-HEP-1	Liver and intrahepatic bile duct epithelial neoplasm	Homo sapiens	CVCL_0525
In-vivo Model	Hepatocyte-specific knockout USP48 was obtained by crossing Alb-Cre mice with USP48^flox/flox mice.
Response Summary	Methyltransferase-like 14 (Mettl14)-induced m6A modification participated in the regulation of Ubiquitin carboxyl-terminal hydrolase 48 (USP48) in hepatocellular carcinoma by maintaining USP48 mRNA stability. This work uncovers the tumor-suppressive function of the Mettl14-USP48-SIRT6 axis via modulation of glycolysis, providing new insights into the critical roles of metabolic activities in HCC and identifying an attractive target for future treatment studies.

HLA complex group 11 (HCG11)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL14*
Cell Line	MDA-MB-231	Homo sapiens
Treatment: siMETTL14 MDA-MB-231 cells Control: MDA-MB-231 cells		GSE81164
Regulation		logFC: -6.19E-01 p-value: 1.66E-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				[59]
Responsed Disease	Lung adenocarcinoma [ICD-11: 2C25.0]
Target Regulation	Down regulation
Pathway Response	Nucleotide excision repair			hsa03420
Cell Process	RNA stabilization
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	HBE (Human bronchial epithelial cell line)
	NCI-H1975	Lung adenocarcinoma	Homo sapiens	CVCL_1511
	NCI-H522	Lung adenocarcinoma	Homo sapiens	CVCL_1567
	PC-9	Lung adenocarcinoma	Homo sapiens	CVCL_B260
In-vivo Model	LUAD cells stably HCG11 and/or LATS1 overexpressed or silenced were subcutaneously injected into the flank of the BALB/c nude mice (male, 4 weeks old).
Response Summary	HLA complex group 11 (HCG11) mediated by METTL14 inhibited the growth of lung adenocarcinoma via IGF2BP2/LATS1. The m6A modification of HCG11 promoted its nuclear exportation and binding by Insulin Like Growth Factor 2 MRNA Binding Protein 2 (IGF2BP2), resulting in increased stability.

Nuclear paraspeckle assembly transcript 1 (NEAT1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL14*
Cell Line	MDA-MB-231	Homo sapiens
Treatment: siMETTL14 MDA-MB-231 cells Control: MDA-MB-231 cells		GSE81164
Regulation		logFC: -8.94E-01 p-value: 3.90E-11
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				[60]
Responsed Disease	Renal cell carcinoma [ICD-11: 2C90]
Target Regulation	Down regulation
Cell Process	Cell proliferation and metastasis
In-vitro Model	769-P	Renal cell carcinoma	Homo sapiens	CVCL_1050
	786-O	Renal cell carcinoma	Homo sapiens	CVCL_1051
	HK2	Normal	Acipenser baerii	CVCL_YE28
In-vivo Model	Mouse subcutaneous xenograft and lung metastasis experiments were carried out with six 4-week-old male BALB/c nude mice.
Response Summary	In renal cell carcinoma, YTHDF2 accelerated the degradation of Nuclear paraspeckle assembly transcript 1 (NEAT1)_1 by selectively recognizing METTL14-mediated m6A marks on Nuclear paraspeckle assembly transcript 1 (NEAT1)_1.

Coronary atherosclerosis [ICD-11: BA52]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[103]
Responsed Disease	Coronary atherosclerosis [ICD-11: BA52.0]
Target Regulation	Up regulation

Atherosclerosis [ICD-11: BD40]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[103]
Responsed Disease	Atherosclerosis [ICD-11: BD40]
Target Regulation	Up regulation

Aspartate--tRNA ligase, cytoplasmic (DARS)

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				[61]
Responsed Disease	Cervical cancer [ICD-11: 2C77]
Pathway Response	Autophagy			hsa04140
Cell Process	Cell autophagy
In-vitro Model	SiHa	Cervical squamous cell carcinoma	Homo sapiens	CVCL_0032
	HeLa	Endocervical adenocarcinoma	Homo sapiens	CVCL_0030
	End1/E6E7	Normal	Homo sapiens	CVCL_3684
	DoTc2 4510	Cervical carcinoma	Homo sapiens	CVCL_1181
	Ca Ski	Cervical squamous cell carcinoma	Homo sapiens	CVCL_1100
	C-33 A	Cervical squamous cell carcinoma	Homo sapiens	CVCL_1094
Response Summary	DARS-AS1 was validated to facilitate DARS translation via recruiting METTL3 and METTL14, which bound with DARS mRNA Aspartate--tRNA ligase, cytoplasmic (DARS) mRNA 5' untranslated region (5'UTR) and promoting its translation. The present study demonstrated that the 'HIF1-Alpha/DARS-AS1/DARS/ATG5/ATG3' pathway regulated the hypoxia-induced cytoprotective autophagy of cervical cancer(CC) and is a promising target of therapeutic strategies for patients afflicted with CC.

Basic leucine zipper transcriptional factor ATF-like 2 (BATF2)

Target Gene

Malignant neoplasms tongue [ICD-11: 2B62]

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 neoplasms tongue [ICD-11: 2B62.0]
Target Regulation	Down regulation
In-vitro Model	SCC-15	Tongue squamous cell carcinoma	Homo sapiens	CVCL_1681
	CAL-27	Tongue squamous cell carcinoma	Homo sapiens	CVCL_1107
	HUVEC-C	Normal	Homo sapiens	CVCL_2959
In-vivo Model	BALB/c nude mice (aged 4-6 weeks) were fed under specific pathogen-free conditions at 26-28°C under 40-60% humidity. For tumorigenicity assay in vivo, CAL-27 cells transfected with BATF2 overexpression plasmids or empty plasmids or untreated CAL-27 cells were subcutaneously inoculated into the right armpit of mice. Following 4 weeks, mice were sacrificed by cervical dislocation under isoflurane anesthesia and neoplasms were isolated and weighted. The volume of neoplasms was monitored once a week. For the in vivo metastasis model, the tail vein of mice was intravenously injected with BATF2-overexpressed or control CAL-27 cells or untreated CAL-27 cells.

Cadherin-1 (CDH1)

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				[64]
Responsed Disease	Esophageal Squamous Cell Carcinoma [ICD-11: 2B70.1]
In-vitro Model	Eca-109	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_6898
In-vitro Model	KYSE-30	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1351

Cellular tumor antigen p53 (TP53/p53)

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				[10]
Responsed Disease	Acute myeloid leukaemia [ICD-11: 2A60]
Target Regulation	Down regulation
Pathway Response	p53 signaling pathway			hsa04115
	Cell cycle			hsa04110
	Apoptosis			hsa04210
Cell Process	Cell apoptosis
Cell Process	Cells in G6/M phase decreased
In-vitro Model	THP-1	Childhood acute monocytic leukemia	Homo sapiens	CVCL_0006
	NB4	Acute promyelocytic leukemia	Homo sapiens	CVCL_0005
	MV4-11	Childhood acute monocytic leukemia	Homo sapiens	CVCL_0064
	MOLT-4	Adult T acute lymphoblastic leukemia	Homo sapiens	CVCL_0013
	Kasumi-1	Myeloid leukemia with maturation	Homo sapiens	CVCL_0589
	K-562	Chronic myelogenous leukemia	Homo sapiens	CVCL_0004
	HL-60	Adult acute myeloid leukemia	Homo sapiens	CVCL_0002
	HEL	Erythroleukemia	Homo sapiens	CVCL_0001
	CCRF-CEM C7	T acute lymphoblastic leukemia	Homo sapiens	CVCL_6825
	HEK293T	Normal	Homo sapiens	CVCL_0063
Response Summary	METTL3 and METTL14 play an oncogenic role in acute myeloid leukemia(AML) by targeting mdm2/Cellular tumor antigen p53 (TP53/p53) signal pathway. The knockdown of METTL3 and METTL14 in K562 cell line leads to several changes in the expression of p53 signal pathway, including the upregulation of p53, cyclin dependent kinase inhibitor 1A (CDKN1A/p21), and downregulation of mdm2.

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				[67]
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulation	Up regulation
Pathway Response	Drug metabolism - cytochrome P450			hsa00982
Cell Process	Drug-metabolizing
In-vitro Model	HepaRG	Hepatitis C infection	Homo sapiens	CVCL_9720
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.

E3 ubiquitin-protein ligase Mdm2 (Mdm2)

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				[10]
Responsed Disease	Acute myeloid leukaemia [ICD-11: 2A60]
Target Regulation	Up regulation
Pathway Response	p53 signaling pathway			hsa04115
Pathway Response	Cell cycle			hsa04110
Cell Process	Cell apoptosis
Cell Process	Cells in G5/M phase decreased
In-vitro Model	THP-1	Childhood acute monocytic leukemia	Homo sapiens	CVCL_0006
	NB4	Acute promyelocytic leukemia	Homo sapiens	CVCL_0005
	MV4-11	Childhood acute monocytic leukemia	Homo sapiens	CVCL_0064
	MOLT-4	Adult T acute lymphoblastic leukemia	Homo sapiens	CVCL_0013
	Kasumi-1	Myeloid leukemia with maturation	Homo sapiens	CVCL_0589
	K-562	Chronic myelogenous leukemia	Homo sapiens	CVCL_0004
	HL-60	Adult acute myeloid leukemia	Homo sapiens	CVCL_0002
	HEL	Erythroleukemia	Homo sapiens	CVCL_0001
	CCRF-CEM C7	T acute lymphoblastic leukemia	Homo sapiens	CVCL_6825
	HEK293T	Normal	Homo sapiens	CVCL_0063
Response Summary	METTL3 and METTL14 play an oncogenic role in acute myeloid leukemia(AML) by targeting E3 ubiquitin-protein ligase Mdm2 (Mdm2)/p53 signal pathway. The knockdown of METTL3 and METTL14 in K562 cell line leads to several changes in the expression of p53 signal pathway, including the upregulation of p53, cyclin dependent kinase inhibitor 1A (CDKN1A/p21), and downregulation of mdm2.

E3 ubiquitin-protein ligase TRIM11 (TRIM11)

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		[69]
Responsed Disease	Cervical cancer [ICD-11: 2C77]
Target Regulation	Up regulation

Epithelial splicing regulatory protein 2 (ESRP2)

Target Gene

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				[70]
Responsed Disease	Renal cell carcinoma of kidney [ICD-11: 2C90.0]
Target Regulation	Up regulation
Pathway Response	Ubiquitin mediated proteolysis			hsa04120
Cell Process	Ubiquitination
In-vitro Model	OS-RC-2	Clear cell renal cell carcinoma	Homo sapiens	CVCL_1626
	Caki-1	Clear cell renal cell carcinoma	Homo sapiens	CVCL_0234
	786-O	Renal cell carcinoma	Homo sapiens	CVCL_1051
In-vivo Model	For the xenograft tumor model, approximately 1 × 10⁶ ccRCC cells suspended in 100 uL PBS were subcutaneously inoculated in the right flank of 5-week-old BALB/c nude mice. For the ccRCC orthotopic implantation model, approximately 1 × 10⁶ ccRCC cells suspended in 30 uL Matrigel were injected under the renal capsule of 5-week-old BALB/c nude mice. After 6 weeks, the anesthetized mice were intraperitoneally injected with D-luciferin (Yeason) and imaged using an in vivo imaging system to detect tumor growth and metastasis. For the lung metastasis model, approximately 5 × 10⁵ ccRCC cells suspended in PBS were injected into the tail vein of 5-week-old mice. After 6-8 weeks, mice were anesthetized and lung metastasis was imaged as above.
Response Summary	The expression of METTL14 was negatively correlated to the prognosis, stage, and ccRCC tumor grade. Lnc-LSG1 could be regulated by METTL14. Lnc-LSG1 can directly bind to Epithelial splicing regulatory protein 2 (ESRP2) protein and promote ESRP2 degradation via facilitating ESRP2 ubiquitination.

Hepatocyte nuclear factor 1-alpha (HNF1A/TCF1)

Target Gene

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				[72]
Responsed Disease	Osteoporosis [ICD-11: FB83.1]
Target Regulation	Up regulation
In-vitro Model	MC3T3-E1	Normal	Mus musculus	CVCL_0409

Hypoxia-inducible factor 1-alpha (HIF-1-Alpha/HIF1A)

Target Gene

Psoriasis [ICD-11: EA90]

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	Psoriasis [ICD-11: EA90]
Target Regulation	Down regulation
In-vitro Model	HaCaT	Normal	Homo sapiens	CVCL_0038
	HUVEC-C	Normal	Homo sapiens	CVCL_2959
	HEK293	Normal	Homo sapiens	CVCL_0045

Insulin receptor substrate 1 (IRS1)

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]

LIM and SH3 domain protein 1 (LASP1)

Target Gene

Rheumatoid arthritis [ICD-11: FA20]

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	Rheumatoid arthritis [ICD-11: FA20]
Target Regulation	Up regulation

Mammalian target of rapamycin complex 2 (mTORC2)

Target Gene

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				[42]
Responsed Disease	Endometrial cancer [ICD-11: 2C76]
Target Regulation	Down regulation
In-vitro Model	HEC-1-A	Endometrial adenocarcinoma	Homo sapiens	CVCL_0293
In-vivo Model	4×10⁶ HEC-1-A endometrial cancer cells (shCtrl, shMETTL3, wild-type, METTL14^+/-, or METTL14^+/- rescued with wild-type or mutant METTL14) were injected intraperitoneally into 5 week old female athymic nude mice (Foxn1^nu, Harlan; n=10 per group).
Response Summary	About 70% of endometrial tumours exhibit reductions in m6A methylation that are probably due to either this METTL14 mutation or reduced expression of METTL3. Reductions in m6A methylation lead to decreased expression of the negative AKT regulator PHLPP2 and increased expression of the positive AKT regulator Mammalian target of rapamycin complex 2 (mTORC2). these results reveal reduced m6A mRNA methylation as an oncogenic mechanism in endometrial cancer and identify m6A methylation as a regulator of AKT signalling.

MAP kinase signal-integrating kinase 2 (MNK2)

Target Gene

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				[19]
Responsed Disease	Muscular dystrophies [ICD-11: 8C70]
Target Regulation	Up regulation
Pathway Response	MAPK signaling pathway			hsa04010
In-vitro Model	HEK293T	Normal	Homo sapiens	CVCL_0063
In-vitro Model	C2C12	Normal	Mus musculus	CVCL_0188
In-vivo Model	For mouse muscle injury and regeneration experiment, tibialis anterior (TA) muscles of 6-week-old male mice were injected with 25 uL of 10 uM cardiotoxin (CTX, Merck Millipore, 217503), 0.9% normal saline (Saline) were used as control. The regenerated muscles were collected at day 1, 3, 5, and 10 post-injection. TA muscles were isolated for Hematoxylin and eosin staining or frozen in liquid nitrogen for RNA and protein extraction.
Response Summary	m6A writers METTL3/METTL14 and the m6A reader YTHDF1 orchestrate MAP kinase signal-integrating kinase 2 (MNK2) expression posttranscriptionally and thus control ERK signaling, which is required for the maintenance of muscle myogenesis and contributes to regeneration.

Microprocessor complex subunit DGCR8 (DGCR8)

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				[76]
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulation	Up regulation
Cell Process	Tumor metastasis
In-vitro Model	HCC-1664 cell line (Primary HCC cells)
	Hep 3B2.1-7	Childhood hepatocellular carcinoma	Homo sapiens	CVCL_0326
	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
	SMMC-7721	Endocervical adenocarcinoma	Homo sapiens	CVCL_0534
	SMMC-7721	Endocervical adenocarcinoma	Homo sapiens	CVCL_0534
In-vivo Model	Male athymic BALB/c nude mice (5 weeks old) were used. Subcutaneous tumor growth assays, liver metastasis model, and tail vein injection model were performed as described.Metastases were detected using the IVIS@Lumina II system (Caliper Life Sciences, Hopkinton, MA) 10 minutes after intraperitoneal injection of 4.0 mg luciferin (Gold Biotech) in 50 uL of saline.
Response Summary	METTL14 interacts with the microprocessor protein Microprocessor complex subunit DGCR8 (DGCR8) and positively modulates the primary microRNA 126 process in an m6 A-dependent manner. microRNA 126 inhibits the repressing effect of METTL14 in Hepatocellular carcinoma metastasis.

NACHT, LRR and PYD domains-containing protein 3 (NLRP3)

Target Gene

Insulin resistance [ICD-11: 5A44]

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	Insulin resistance [ICD-11: 5A44]
Target Regulation	Up regulation
In-vitro Model	L-02	Endocervical adenocarcinoma	Homo sapiens	CVCL_6926

Intervertebral disc degeneration [ICD-11: FA80]

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	Intervertebral disc degeneration [ICD-11: FA80]

Injury of other or unspecified intrathoracic organs [ICD-11: NB32]

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	Injury of other or unspecified intrathoracic organs [ICD-11: NB32.3]
Target Regulation	Down regulation
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
In-vivo Model	The mice were divided into four groups: sham group, cecal ligation and puncture (CLP) group, CLP + lentivirus short hairpin RNA NC (lv-shNC) group, CLP + lentivirus short hairpin RNA METTL14 (lv-shMETTL4) group. The CLP assay was used to establish the sepsis-induced ALI model. In brief, mice were fasted for 12 h before surgery and were anesthetized by intraperitoneal injection of 10% chloral hydrate (3 mL/kg). Mice were fixed in a supine position, and after abdominal disinfection, an incision of about 1 cm was made along the midline of the abdominal wall. Then, the cecum was separated and penetrated using 18-gauge needle for three times. After that, the punctured cecum was returned to the abdominal cavity, and the abdominal incision was sutured layer by layer. The mice in the sham group were subjected to the same procedure without puncture treatment. For METTL14 knockdown globally, lentivirus (lv) containing shMETTL14 and shNC (0.2 ml, 1 × 109 pfu/ml) were injected into the caudal vein 4 days before modeling, respectively.

NAD-dependent protein deacetylase sirtuin-6 (SIRT6)

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				[58]
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulation	Up regulation
Pathway Response	Ubiquitin mediated proteolysis			hsa04120
	Glycolysis / Gluconeogenesis			hsa00010
Cell Process	Ubiquitination degradation
	Glycolysis
In-vitro Model	BEL-7404	Endocervical adenocarcinoma	Homo sapiens	CVCL_6568
	Huh-7	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0336
	SK-HEP-1	Liver and intrahepatic bile duct epithelial neoplasm	Homo sapiens	CVCL_0525
	SK-HEP-1	Liver and intrahepatic bile duct epithelial neoplasm	Homo sapiens	CVCL_0525
In-vivo Model	Hepatocyte-specific knockout USP48 was obtained by crossing Alb-Cre mice with USP48^flox/flox mice.
Response Summary	Methyltransferase-like 14 (Mettl14)-induced m6A modification participated in the regulation of USP48 in hepatocellular carcinoma by maintaining USP48 mRNA stability. This work uncovers the tumor-suppressive function of the Mettl14-USP48-NAD-dependent protein deacetylase sirtuin-6 (SIRT6) axis via modulation of glycolysis, providing new insights into the critical roles of metabolic activities in HCC and identifying an attractive target for future treatment studies.

Nuclear factor NF-kappa-B p105 subunit (NF-Kappa-B/NFKB1)

Target Gene

Atherosclerosis [ICD-11: BD40]

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	Atherosclerosis [ICD-11: BD40.Z]
Target Regulation	Up regulation
Pathway Response	IL-17 signaling pathway			hsa04657
In-vitro Model	THP-1	Childhood acute monocytic leukemia	Homo sapiens	CVCL_0006
In-vivo Model	Mettl14 heterozygous mice (Mettl14^-/+) were established from C57/BL6 mice by Cyagen Biosciences, Inc. (Suzhou, Jiangsu, China), using CRISPR/Cas9-based targeting and homology-directed repair. C57/BL6 and APOE^-/- mice were purchased from Beijing Vital River Laboratory Animal Technology (Beijing, China). Mettl14^-/+APOE^-/- mice were generated by breeding Mettl14^-/+ mice with APOE^-/- mice. Eight- to 10-week-old male APOE^-/- (WT) mice and Mettl14^-/+APOE^-/- (KO) mice were fed a high-cholesterol diet (D12108C, Opensource diets) for 12 weeks. Then, the mice were euthanized for further analysis.
Response Summary	Mettl14 gene knockout significantly reduced the inflammatory response of macrophages and the development of atherosclerotic plaques, Mettl14 plays a vital role in macrophage inflammation in atherosclerosis via the Nuclear factor NF-kappa-B p105 subunit (NF-Kappa-B/NFKB1)/IL-6 signaling pathway.

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		[81]
Responsed Disease	Nonalcoholic steatohepatitis [ICD-11: DB92.1]
Target Regulation	Up regulation
In-vitro Model	KCs (Mouse Kupffer cells (BeNa Culture Collection, Beijing, China; BNCC340733))
In-vivo Model	At 8 weeks of age, METTL14 cKO and WT mice were challenged with LPS (Sigma-Aldrich, St. Louis, MO; L2880, single intraperitoneal injection at 5 mg/kg, n = 3) or CCl4 (10%, Macklin, Shanghai, China; C805332, intraperitoneal injection at 5 mL/kg diluted with corn oil, twice per week for 4 weeks, n = 3). The corresponding control groups were treated with single intraperitoneal injection of saline (n = 3) or intraperitoneal injection of corn oil twice per week for 4 weeks (n = 3), respectively. Two hours after LPS injection and 4 weeks after CCl4 treatment, METTL14 cKO and WT mice were etherized and the primary KCs were isolated from liver according to a previously published method.
Response Summary	Nuclear factor NF-kappa-B p105 subunit (NF-Kappa-B/NFKB1) acts as transcription factor to transactivate METTL3/METTL14 genes upon LPS challenge, leading to global RNA m6A hypermethylation. m6A modification in TGF-beta1 upregulation, which helps to shed light on the molecular mechanism of nonalcoholic steatohepatitis(NASH) progression.

P2X purinoceptor 6 (P2RX6)

Target Gene

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				[82]
Responsed Disease	Renal cell carcinoma [ICD-11: 2C90]
Target Regulation	Down regulation
Cell Process	Cell invasion and metastasis
In-vitro Model	SW839	Clear cell renal cell carcinoma	Homo sapiens	CVCL_3604
	SN12C-PM6	Renal cell carcinoma	Homo sapiens	CVCL_9549
	OS-RC-2	Clear cell renal cell carcinoma	Homo sapiens	CVCL_1626
	HEK293	Normal	Homo sapiens	CVCL_0045
	786-O	Renal cell carcinoma	Homo sapiens	CVCL_1051
In-vivo Model	For the in vivo metastasis assays, luciferase labeled OS-RC-2 cells stably expressing OE-P2RX6 or pWPI-vector were injected into the tail vein of 5 weeks old BALB/c nude mice (Sipper-BK laboratory animal Company, Shanghai, China).
Response Summary	In RCC, METTL14 implicated m6A modification in RCC and down-regulated P2X purinoceptor 6 (P2RX6) protein translation.

Pescadillo homolog (PES1)

Target Gene

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				[84]
Responsed Disease	Chronic myeloid leukaemia [ICD-11: 2B33.2]
Target Regulation	Down regulation
Pathway Response	Cell cycle			hsa04110
Cell Process	Decrease of S phase
In-vitro Model	U-937	Adult acute monocytic leukemia	Homo sapiens	CVCL_0007
	NB4	Acute promyelocytic leukemia	Homo sapiens	CVCL_0005
	LAMA-84	Chronic myelogenous leukemia	Homo sapiens	CVCL_0388
	KCL-22	Chronic myelogenous leukemia	Homo sapiens	CVCL_2091
	K-562	Chronic myelogenous leukemia	Homo sapiens	CVCL_0004
	HL-60	Adult acute myeloid leukemia	Homo sapiens	CVCL_0002
	HEL	Erythroleukemia	Homo sapiens	CVCL_0001
Response Summary	m6A methyltransferase complex METTL3/METTL14 is upregulated in CML patients and that is required for proliferation of primary CML cells and CML cell lines sensitive and resistant to the TKI imatinib. METTL3 directly regulates the level of Pescadillo homolog (PES1) protein identified as an oncogene in several tumors. These results point to METTL3 as a novel relevant oncogene in CML and as a promising therapeutic target for TKI resistant CML.

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

Target Gene

Diabetic [ICD-11: 5A14]

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	Diabetic [ICD-11: 5A14]
Responsed Drug	Arsenite		Phase 2	Drug Info
In-vitro Model	L-02	Endocervical adenocarcinoma	Homo sapiens	CVCL_6926

Proto-oncogene Wnt-1 (Wnt1)

Target Gene

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		[9]
Responsed Disease	Ischemic heart disease [ICD-11: BA40-BA6Z]
Target Regulation	Up regulation
Pathway Response	Wnt signaling pathway	hsa04310
In-vitro Model	Neonatal rat ventricular cardiomyocytes (Primary myocyte cells)
In-vivo Model	C57BL/6 mouse hearts were subjected to ischemia/reperfusion (I/R) in vivo as described previously (Bock-Marquette et al., 2004; Song et al., 2015; Brocard et al., 2017). I/R injury in mice was induced by 45-min ischemia, followed by 7-day and 4-week reperfusion in a loss-of-function study (Figure 1) and gain-of-function study (Figure 2), respectively. In brief, mice were anesthetized with 2% avertin (0.1 ml/10g body weight; Sigma-Aldrich Corporation, United States) through intraperitoneal injection. To generate I/R injury, the left anterior descending coronary artery (LAD) was ligated with 7-0 nylon for 45 min and then was removed. For the sham group, a suture was passed under the LAD but without ligation. According to the experimental requirements, at different time points of cardiac I/R, the mice were anesthetized for assessing heart function by echocardiographic measurement. All the mice survived during the process of I/R injury after the operation.
Response Summary	Mettl14 resulted in enhanced levels of Proto-oncogene Wnt-1 (Wnt1) m6A modification and Wnt1 protein but not its transcript level. Furthermore, Mettl14 overexpression blocked I/R-induced downregulation of Wnt1 and Bete-catenin proteins, whereas Mettl14 hearts exhibited the opposite results. Mettl14 attenuates cardiac I/R injury by activating Wnt/Bete-catenin in an m6A-dependent manner, providing a novel therapeutic target for ischemic heart disease.

Protocadherin Fat 4 (FAT4)

Target Gene

Melanoma of uvea [ICD-11: 2D0Y]

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	Melanoma of uvea [ICD-11: 2D0Y]
Target Regulation	Up regulation
In-vitro Model	Mel290	Uveal melanoma	Homo sapiens	CVCL_C304
	OMM2.3	Uveal melanoma	Homo sapiens	CVCL_C306
	OMM-1	Uveal melanoma	Homo sapiens	CVCL_6939
	CRMM-1	Conjunctival melanoma	Homo sapiens	CVCL_M593
	CRMM-2	Conjunctival melanoma	Homo sapiens	CVCL_M594
	CM2005.1	Conjunctival melanoma	Homo sapiens	CVCL_M592
	MuM-2B	Uveal melanoma	Homo sapiens	CVCL_3447
	92-1 [Human uveal melanoma]	Uveal melanoma	Homo sapiens	CVCL_8607
	ARPE-19	Normal	Homo sapiens	CVCL_0145
	A-375	Amelanotic melanoma	Homo sapiens	CVCL_0132
	SK-MEL-28	Cutaneous melanoma	Homo sapiens	CVCL_0526
	PIG1	Normal	Homo sapiens	CVCL_S410

Ras-related protein Rab-22A (RAB22A)

Target Gene

Atherosclerosis [ICD-11: BD40]

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	Atherosclerosis [ICD-11: BD40.Z]

RB1-inducible coiled-coil protein 1 (RB1CC1/FIP200)

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				[88]
Responsed Disease	Oral squamous cell carcinoma [ICD-11: 2B6E.0]
Target Regulation	Up regulation
In-vitro Model	CAL-33	Tongue squamous cell carcinoma	Homo sapiens	CVCL_1108
In-vivo Model	Thirty-six specific pathogen-free male BALB/c-nude mice (age, 5-6 weeks) were randomly assigned to the groups: CAL33/shMETTL14#2, CAL33/shMETTL14#3, CAL33/shNC and HSC3/shMETTL14#2, HSC3/shMETTL14#3, HSC3/shNC (n = 6 per group). Fifty microliters of PBS buffer containing approximately 1 × 10⁶ cells was injected into the left tongue under 2% pentobarbital sodium intraperitoneal injection anesthesia to establish a tumor xenograft. The weight of the mice was measured every 3 days after one week until they lost more than 15% of their body weight in a short period of time.

Sequestosome-1 (SQSTM1)

Target Gene

Breast cancer [ICD-11: 2C60]

In total 2 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	Paclitaxel		Approved	Drug Info
In-vitro Model	HEK293T	Normal	Homo sapiens	CVCL_0063
In-vivo Model	The experimental mice were housed in an SPF-grade animal laboratory at a temperature of approximately 25 °C, a humidity range of 50%, and an average daylight duration of 12 h. BALB/C female mice at 5-7 weeks of age were taken and prepared for tumor-bearing. After the mice were sacrificed, their tissues were collected, weighed and immediately snap-frozen in liquid nitrogen.
Experiment 2 Reporting the m6A-centered Disease Response of This Target Gene				[89]
Responsed Disease	Breast cancer [ICD-11: 2C60]
Responsed Drug	STM2457		Investigative	Drug Info
In-vitro Model	HEK293T	Normal	Homo sapiens	CVCL_0063
In-vivo Model	The experimental mice were housed in an SPF-grade animal laboratory at a temperature of approximately 25 °C, a humidity range of 50%, and an average daylight duration of 12 h. BALB/C female mice at 5-7 weeks of age were taken and prepared for tumor-bearing. After the mice were sacrificed, their tissues were collected, weighed and immediately snap-frozen in liquid nitrogen.

Serine/threonine-protein kinase mTOR (MTOR)

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				[43]
Responsed Disease	Gastric cancer [ICD-11: 2B72]
Target Regulation	Down regulation
Pathway Response	PI3K-Akt signaling pathway			hsa04151
Pathway Response	mTOR signaling pathway			hsa04150
In-vitro Model	SGC-7901	Gastric carcinoma	Homo sapiens	CVCL_0520
	MGC-803	Gastric mucinous adenocarcinoma	Homo sapiens	CVCL_5334
	GES-1	Normal	Homo sapiens	CVCL_EQ22
Response Summary	The m6A modification level was decreased in GC and METTL14 was a key regulator resulting in m6A disorder in GC. METTL14 overexpression suppressed GC cell proliferation and aggression by deactivating the PI3K/AKT/Serine/threonine-protein kinase mTOR (MTOR) pathway and the EMT pathway, respectively.

Signal transducer and activator of transcription 3 (STAT3)

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				[90]
Responsed Disease	Gastric cancer [ICD-11: 2B72]
In-vitro Model	GES-1	Normal	Homo sapiens	CVCL_EQ22
	AGS	Gastric adenocarcinoma	Homo sapiens	CVCL_0139
	HGC-27	Gastric carcinoma	Homo sapiens	CVCL_1279
In-vivo Model	Male nude mice (age: 4 weeks) were obtained from Charles River (Hangzhou, Zhejiang, China). For tumorigenesis analysis, AGS cells (1 × 10⁶) with stable knockdown of AGAP2-AS1 or scramble, were injected into mice. Next, we detected and measured the tumor volume each week. The weight of the tumor in each nude mouse was also measured at 4 weeks after injection. Immunohistochemistry (IHC) was used to detect Ki67- and caspase-3- positive cells in the tumor.

Suppressor of cytokine signaling 3 (SOCS3)

Target Gene

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		[93]
Responsed Disease	Papillary thyroid cancer [ICD-11: 2D10.1]

TNF alpha-induced protein 3 (TNFAIP3)

Target Gene

Rheumatoid arthritis [ICD-11: FA20]

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	Rheumatoid arthritis [ICD-11: FA20]
In-vivo Model	All animal experiments were performed in accordance with Institutional Animal Care and Use Committee guidelines. Six- to eight-week-old male DBA/1J mice (n = 5 per group) were purchased from the Shanghai Laboratory Animal Center, Chinese Academy of Science. All of mice were fed in the specific pathogen free-animal laboratory of the Experimental Animal Center of Fujian Medical University. Animals were housed under controlled conditions with a 12-hour light/dark cycle and with food/water access ad libitum.

Ubiquitin domain-containing protein TINC (TINCR)

Target Gene

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				[96]
Responsed Disease	Diabetic cardiomyopathy [ICD-11: BC43.7]
Target Regulation	Down regulation
In-vitro Model	neonatal ventricular myocytes (Mouse hearts were enzymatically digested to acquire the primary neonatal ventricular myocytes)
	H9c2(2-1)	Normal	Rattus norvegicus	CVCL_0286
In-vivo Model	The diabetic model was constructed by a single intraperitoneal injection of streptozotocin (65 mg/kg), which imitates a model of type 1 diabetes. The fasting blood glucose was measured one week after injection. Only rats with glucose levels higher than 16.7 mmol/L were defined as diabetic. Cardiac function was investigated seven days following the last treatment, and the heart tissues were then isolated for expression analyses. The lentivirus vector used for silencing or overexpressing specific genes were dissolved in 50uL saline at the concentration of 1 × 10⁹ TU with one dose after the animal model was established. NLRP3 inhibitor MCC950 (10 mg/kg) was intraperitoneally injected 30 min before streptozotocin treatment.
Response Summary	METTL14 suppressed pyroptosis and diabetic cardiomyopathy via downregulating lncRNA Ubiquitin domain-containing protein TINC (TINCR), which further decreased the expression of key pyroptosis-related protein, NLRP3.

Ubiquitin-like modifier-activating enzyme ATG7 (ATG7)

Target Gene

Retinopathy [ICD-11: 9B71]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[97]
Responsed Disease	Retinopathy [ICD-11: 9B71]
Target Regulation	Down regulation
In-vivo Model	Seven-day-old C57BL/6J mice and their lactating mothers were exposed to a 75 % oxygen environment in a chamber for a period of 5 days. Subsequently, the mice were transferred to normal room air (21 % oxygen) at postnatal day 12 (P12) and kept under these conditions for an additional 5 days. At P17, the mice were sacrificed by 10 min following an intraperitoneal injection of a mixture of ketamine (100 mg/kg) and xylazine (10 mg/kg), and their eyes were enucleated and processed for immunostaining or immunoblotting.

H19 imprinted maternally expressed transcript (H19)

Target Gene

Abnormalities of breathing [ICD-11: MD11]

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	Abnormalities of breathing [ICD-11: MD11]
Target Regulation	Up regulation
Cell Process	Cell viability
	Cell apoptosis
In-vitro Model	H9c2(2-1)	Normal	Rattus norvegicus	CVCL_0286
In-vivo Model	In vivo myocardial I/R injury was performed by 60 min of ligation of LAD followed by 5 h of reperfusion.
Response Summary	Either knockdown of METTL3 or METTL14 notably reversed the hypoxic preconditioning-induced enhancement of cell viability, anti-apoptosis ability, and H19 imprinted maternally expressed transcript (H19) expression.

LncRNA activating regulator of DKK1 (LNCAROD)

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				[99]
Responsed Disease	Head and neck squamous carcinoma [ICD-11: 2B6E]
Target Regulation	Up regulation
Pathway Response	Proteasome			hsa03050
Cell Process	Proteasomal degradation
In-vitro Model	C666-1	Nasopharyngeal carcinoma	Homo sapiens	CVCL_7949
	CAL-27	Tongue squamous cell carcinoma	Homo sapiens	CVCL_1107
	FaDu	Hypopharyngeal squamous cell carcinoma	Homo sapiens	CVCL_1218
	HK1	Nasopharyngeal carcinoma	Acipenser baerii	CVCL_YE27
	NP69 (A human immortalized nasopharyngeal epithelial)
	Tca8113	Endocervical adenocarcinoma	Homo sapiens	CVCL_6851
Response Summary	The N6-methyladenosine (m6A) modification mediated by METTL3 and METTL14 enhanced the stability of LncRNA activating regulator of DKK1 (LNCAROD) in head and neck squamous cell carcinoma cells. LNCAROD is stabilized by m6A methylation and promotes cancer progression via forming a ternary complex with HSPA1A and YBX1 in head and neck squamous cell carcinoma.

Long intergenic non-protein coding RNA 1320 (LINC01320)

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				[100]
Responsed Disease	Gastric cancer [ICD-11: 2B72]
Target Regulation	Up regulation
Cell Process	Cell proliferation
	Cell migration
	Cell invasion
In-vitro Model	AGS	Gastric adenocarcinoma	Homo sapiens	CVCL_0139
	GES-1	Normal	Homo sapiens	CVCL_EQ22
	HGC-27	Gastric carcinoma	Homo sapiens	CVCL_1279
	MKN7	Gastric tubular adenocarcinoma	Homo sapiens	CVCL_1417
	MKN45	Gastric adenocarcinoma	Homo sapiens	CVCL_0434
	NCI-N87	Gastric tubular adenocarcinoma	Homo sapiens	CVCL_1603
Response Summary	In gastric cancer, METTL14 was involved in the m6A modification of LINC01320 and induced the up-regulation of Long intergenic non-protein coding RNA 1320 (LINC01320).

Metastasis associated lung adenocarcinoma transcript 1 (MALAT1)

Target Gene

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				[101]
Responsed Disease	Blood malignancies [ICD-11: 2B33.Y]
Target Regulation	Up regulation
Cell Process	Oncogenic fusion protein expression
In-vitro Model	HEK293T	Normal	Homo sapiens	CVCL_0063
	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
	NB4	Acute promyelocytic leukemia	Homo sapiens	CVCL_0005
In-vivo Model	The NOD-SCID mice were intravenously (tail vein) implanted with sh-RNA-established NB4 cells. Direct injection of 5 × 10⁶ shRNA-transformed NB4 cells into 150 uL of PBS was performed to establish intravenous (tail vein) leukemia.
Response Summary	MALAT1 hijacks both chimeric mRNAs and fusion protein in nuclear speckles during chromosomal translocation and mediates colocalization with METTL14 in an oncogenic fusion protein such as PML-RARalpha. Reducing MALAT1 or m6A methyltransferases and the 'reader' YTHDC1 result in the universal retention of distinct oncogenic gene (PML-RARalpha) mRNAs in nucleus. Targeting the lncRNA-triggered autoregulatory loop to disrupt chimeric mRNA transport represents a new common paradigm for treating blood malignancies.

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				[102]
Responsed Disease	Oral squamous cell carcinoma [ICD-11: 2B6E.0]
Target Regulation	Up regulation
In-vitro Model	SCC-25	Tongue squamous cell carcinoma	Homo sapiens	CVCL_1682
	SCC-15	Tongue squamous cell carcinoma	Homo sapiens	CVCL_1681
	Hs 680.Tg	Normal	Homo sapiens	CVCL_0842
	FaDu	Hypopharyngeal squamous cell carcinoma	Homo sapiens	CVCL_1218
	CAL-27	Tongue squamous cell carcinoma	Homo sapiens	CVCL_1107
In-vivo Model	Lentiviruses containing sh-METTL-14 and its negative control (RiboBio Co., Ltd., Guangzhou, China) were transduced into CAL27 cells and stably transduced cells were screened using puromycin. CAL27 cells (3 × 10⁶ cells/mouse) were subcutaneously inoculated into the posterior flank of each mouse (N = 12/group).
Response Summary	METTL14 and lncRNA Metastasis associated lung adenocarcinoma transcript 1 (MALAT1) were upregulated, and miR-224-5p was downregulated in OSCC tissues and cells. METTL14 induced m6A modification of MALAT1 to upregulate MALAT1.

X inactive specific transcript (XIST)

Target Gene

Diffuse large B-cell lymphomas [ICD-11: 2A81]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[104]
Responsed Disease	Diffuse large B-cell lymphomas [ICD-11: 2A81]
In-vitro Model	OCI-Ly3	Diffuse large B-cell lymphoma activated B-cell type	Homo sapiens	CVCL_8800
	OCI-Ly10	Diffuse large B-cell lymphoma	Homo sapiens	CVCL_8795
	SU-DHL-2	Diffuse large B-cell lymphoma activated B-cell type	Homo sapiens	CVCL_9550
	U-2932	Diffuse large B-cell lymphoma	Homo sapiens	CVCL_1896

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				[105]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulation	Up regulation
Cell Process	Tumorigenicity and metastasis
In-vitro Model	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	HT29	Colon cancer	Mus musculus	CVCL_A8EZ
	LoVo	Colon adenocarcinoma	Homo sapiens	CVCL_0399
	NCM460	Normal	Homo sapiens	CVCL_0460
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
	SW620	Colon adenocarcinoma	Homo sapiens	CVCL_0547
In-vivo Model	For liver metastasis model, mice were anaesthetized and an incision was made through the skin and peritoneum to expose the spleen. 1 × 10⁶ HCT116 cells were injected into the spleen (n = 4 each group).
Response Summary	In colorectal cancer, knockdown of METTL14 substantially abolished m6A level of X inactive specific transcript (XIST) and augmented XIST expression. m6A-methylated XIST was recognized by YTHDF2, a m6A reader protein, to mediate the degradation of XIST.

ZNFX1 antisense RNA 1 (ZFAS1)

Target Gene

Atherosclerosis [ICD-11: BD40]

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	Atherosclerosis [ICD-11: BD40.Z]

microRNA 211 (MIR211)

Target Gene

Lymphoma [ICD-11: 2A70]

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	Lymphoma [ICD-11: 2A70]
Target Regulation	Up regulation
In-vitro Model	CCRF-CEM	T acute lymphoblastic leukemia	Homo sapiens	CVCL_0207
	H9	Sezary syndrome	Homo sapiens	CVCL_1240
	Jurkat	T acute lymphoblastic leukemia	Homo sapiens	CVCL_0065
	SUP-T1	Childhood T lymphoblastic lymphoma	Homo sapiens	CVCL_1714
In-vivo Model	Subcutaneously injected with 5 × 10⁶ Jurkat cells and fed under Specific Pathogen Free (SPF) conditions. One week later, tumor mass was injected once a week with Agomir NC, Agomir-211, Antagomir NC and Antagomir 211, respectively, for three weeks.
Response Summary	microRNA 211 (MIR211) is a novel tumor suppressor in T-cell lymphoblastic lymphoma,it regulated by METTL14. Targeting of miR-211/TCF12 axis is a potential treatment for T-cell lymphoblastic lymphoma patients.

microRNA 375 (MIR375)

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				[107]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulation	Up regulation
Pathway Response	Hippo signaling pathway			hsa04390
Cell Process	Cell growth and metastasis
In-vitro Model	DLD-1	Colon adenocarcinoma	Homo sapiens	CVCL_0248
	FHC	Normal	Homo sapiens	CVCL_3688
	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	HCT 8	Colon adenocarcinoma	Homo sapiens	CVCL_2478
	HT29	Colon cancer	Mus musculus	CVCL_A8EZ
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
	SW620	Colon adenocarcinoma	Homo sapiens	CVCL_0547
In-vivo Model	Six-week-old BALB/c nude mice were purchased from the College of Veterinary Medicine, Yang Zhou University. For the xenografted tumor model, 1 × 10⁷ HCT116 cells in 0.2 mL PBS were subcutaneously injected into BALB/c nude mice, which were randomly divided into four groups (six mice per group). The volume of the tumors was calculated with the following equation: V = 0.5 × (length × width²). For metastasis experiments, 2 × 10⁶ cells in 0.2 mL PBS were injected into the tail vein of nude mice, which were randomly divided into four groups (six mice per group).
Response Summary	METTL14 suppressed Colorectal cancer cell growth, migration, and invasion via the microRNA 375 (MIR375)/YAP1 and miR-375/SP1 pathways.

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		[108]
Responsed Disease	Breast cancer [ICD-11: 2C60]
Target Regulation	Down regulation

Injuries of spine or trunk [ICD-11: ND51]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[12]
Responsed Disease	Injuries of spine or trunk [ICD-11: ND51]
Target Regulation	Up regulation
Pathway Response	mTOR signaling pathway			hsa04150
In-vitro Model	C8-D1A	Normal	Mus musculus	CVCL_6379
In-vitro Model	C8-B4	Normal	Mus musculus	CVCL_6378
In-vivo Model	An incision was made in the skin along the medial dorsal line to the aponeurotic and muscular planes, and the posterior vertebral arches were exposed from T8 to T12. Under the dissection stereomicroscope, 3-mm-long laminectomy was performed on the caudal end of T10 vertebra and the rostral end of T11 vertebra. The Infinite Horizons impactor (Infinite Horizons, L.L.C., Lexington, KY, USA) was adopted to produce the contusion SCI using a force of 60 kdyn/cm². The SCI model rats were established and randomly assigned to SCI model group, ant-NC (negative control, SCI rats treated with lentiviral (lv)-shRNA NC of Mettl14) group and ant-Mettl14 group (SCI rats treated with lv-shRNA of Mettl14). Rats were subjected to laminectomy and then treated with lv-shRNA Mettl14/lv-shRNA-NC (50 ul/day, 100 nmoL/mL; RiboBio, Guangzhou, China) via an intrathecal injection through lumbar puncture for 3 days (0, 1, and 2 days) after 15 min of SCI modelling. In addition, the unmodeled rats were set as sham group.
Response Summary	Mettl14-mediated m6A modification inhibited RASD1 and induced the apoptosis of spinal cord neurons in SCI by promoting the transformation of pri-miR-375 to mature microRNA 375 (MIR375).

microRNA 93 (MIR93)

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				[109]
Responsed Disease	Non-small cell lung cancer [ICD-11: 2C25.Y]
Target Regulation	Up regulation
In-vitro Model	NCI-H460	Lung large cell carcinoma	Homo sapiens	CVCL_0459
	NCI-H520	Lung squamous cell carcinoma	Homo sapiens	CVCL_1566
	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	BEAS-2B	Normal	Homo sapiens	CVCL_0168
In-vivo Model	110⁶ cells/100 L NSCLC cell suspension (oe-NC group, oe-METTL14 + oe-NC group, oe-METTL14 + oe-TXNIP group) were injected into the tail vein. Twenty-four nude mice (8 in each group) were employed. Following the 56th post-injection day, mice were decapitated by decortication. Hematoxylin-eosin (HE) staining was used to identify tumor metastases in the mouse lung tissue .

hsa-miR-146a-5p

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				[110]
Responsed Disease	Breast cancer [ICD-11: 2C60]
Target Regulation	Up regulation
Cell Process	Cell migration and invasion
	Epithelial-mesenchymal transition
In-vitro Model	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
	MDA-MB-231	Breast adenocarcinoma	Homo sapiens	CVCL_0062
Response Summary	In breast cancer, hsa-miR-146a-5p modulated by METTL14 promoted cell migration and invasion.

hsa-miR-19a-3p

Target Gene

Atherosclerosis [ICD-11: BD40]

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	Atherosclerosis [ICD-11: BD40.Z]
Target Regulation	Up regulation
Cell Process	Cell migration and invasion
	Epithelial-mesenchymal transition
In-vitro Model	ASVEC cell line (Atherosclerotic vascular endothelial cells)
Response Summary	METTL14 increased the m6A modification of pri-miR-19a and promoted the processing of mature hsa-miR-19a-3p, thus promoting the proliferation and invasion of atherosclerotic vascular endothelial cells.

hsa-miR-21-5p

Target Gene

Abortion [ICD-11: JA00]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[112]
Responsed Disease	Abortion [ICD-11: JA00.0]
In-vitro Model	HTR-8	Normal	Homo sapiens	CVCL_D728
In-vivo Model	BALB/c mice (female) and C57BL/6 mice (male) (8-12 weeks-old, 20-22 g) were obtained from the Shanghai Laboratory Animal Center (Shanghai, China). Pregnancy day 0.5 (E0.5) was determined by measuring the vaginal plug. The m6A inhibitor, 3-deazaadenosine (40 μL at a concentration of 10 mg/kg dissolved in physiological saline; Sigma-Aldrich, St. Louis, MO, USA) was injected into the uterine cavity using a small catheter (Instech Laboratories, Plymouth Meeting, PA, USA) at E6.5, E5.5, and E4.5, respectively, whereas the control group was injected with an equal volume of saline solution. Mice were sacrificed at E10.5, embryo resorption was measured and photographed, and the placentas were collected. The resorbed embryos were small (<20 % of the average size), appeared dark with unclear boundaries between the fetus and the placenta, and showed necrosis.

hsa-miR-30c-1-3p

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				[113]
Responsed Disease	Lung cancer [ICD-11: 2C25]
Target Regulation	Up regulation
Cell Process	miRNA maturation
In-vitro Model	PC-9	Lung adenocarcinoma	Homo sapiens	CVCL_B260
	NCI-H1975	Lung adenocarcinoma	Homo sapiens	CVCL_1511
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	BEAS-2B	Normal	Homo sapiens	CVCL_0168
	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
In-vivo Model	The cells (1 × 10⁶) were re-suspended in normal saline and mixed with 25% Matrigel matrix (50 uL) at a 1:1 ratio and subcutaneously injected into the right groin of the mice.
Response Summary	METTL14 was remarkably downregulated in LC tissues and cell lines. METTL14 mediated the maturation of hsa-miR-30c-1-3p.

hsa-miR-30c-2-3p

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				[45]
Responsed Disease	Gastric cancer [ICD-11: 2B72]
Target Regulation	Up regulation
In-vitro Model	SGC-7901	Gastric carcinoma	Homo sapiens	CVCL_0520
	MKN28	Gastric tubular adenocarcinoma	Homo sapiens	CVCL_1416
	MGC-803	Gastric mucinous adenocarcinoma	Homo sapiens	CVCL_5334
	GES-1	Normal	Homo sapiens	CVCL_EQ22
	BGC-823	Gastric carcinoma	Homo sapiens	CVCL_3360
	AGS	Gastric adenocarcinoma	Homo sapiens	CVCL_0139
Response Summary	METTL14-mediated m6A modification of circORC5 suppresses gastric cancer progression by regulating hsa-miR-30c-2-3p/AKT1S1 axis.METTL14 was downregulated in GC tissue samples and its low expression acted as a prognostic factor of poor survival in patients with GC.

hsa-miR-380-3p

Target Gene

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				[114]
Responsed Disease	Pancreatic cancer [ICD-11: 2C10]
Target Regulation	Up regulation
Pathway Response	PI3K-Akt signaling pathway			hsa04151
Cell Process	Epithelial-mesenchymal transition
In-vitro Model	HPDE	Normal	Homo sapiens	CVCL_4376
	PANC-1	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0480
	Capan-2	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0026
	SW1990	Pancreatic adenocarcinoma	Homo sapiens	CVCL_1723
	AsPC-1	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0152
	BxPC-3	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0186
In-vivo Model	The PC cell line PANC1 was subcutaneously injected into the dorsal flank of the mice at the concentration of 1 × 10⁶ cells per mouse.
Response Summary	hsa-miR-380-3p was enriched with m6A modifications, and elimination of m6A modifications by deleting METTL3 and METTL14 synergistically suppressed miR-380-3p expressions in pancreatic cancer cells.

hsa-miR-99a-5p

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				[54]
Responsed Disease	Esophageal squamous cell carcinoma [ICD-11: 2B70.1]
Target Regulation	Up regulation
Pathway Response	Ubiquitin mediated proteolysis			hsa04120
Cell Process	Proteasome pathway degradation
In-vitro Model	TE-1	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1759
	KYSE-410	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1352
	KYSE-150	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1348
	HET-1A	Normal	Homo sapiens	CVCL_3702
	HEK293T	Normal	Homo sapiens	CVCL_0063
	Eca-109	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_6898
	CVCL_E307	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_E307
In-vivo Model	Fresh PDX tumor samples collected from two established PDX models (PDX #07 with high TRIB2 expression and PDX #12 with low TRIB2, passages three to four) were minced and subcutaneously implanted into the flanks of 3- to 4-week-old female BALB/c nude mice (Jiesijie Laboratory Animals).
Response Summary	METTL14, an m6A RNA methyltransferase downregulated in ESCC, suppresses TRIB2 expression via hsa-miR-99a-5p-mediated degradation of TRIB2 mRNA by targeting its 3' untranslated region, whereas TRIB2 induces ubiquitin-mediated proteasomal degradation of METTL14 in a COP1-dependent manner.

hsa_circ_0008399 (Circ_RBM3)

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				[115]
Responsed Disease	Bladder cancer [ICD-11: 2C94]
Responsed Drug	Cisplatin		Approved	Drug Info
Target Regulation	Up regulation
Pathway Response	Protein export			hsa03060
Cell Process	Eukaryotic translation
	Cell apoptosis
In-vitro Model	5637	Bladder carcinoma	Homo sapiens	CVCL_0126
	RT-4	Bladder carcinoma	Homo sapiens	CVCL_0036
	UM-UC-3	Bladder carcinoma	Homo sapiens	CVCL_1783
In-vivo Model	Chose 4-week-old female BALB/c nude mice for tumor xenograft experiments, which randomly were divided into four groups (n = 5 per group). Bladder cancer cells (3 × 10⁶) were subcutaneously injected into the right axilla of the nude mice.
Response Summary	Circ0008399 bound WTAP to promote formation of the WTAP/METTL3/METTL14 m6A methyltransferase complex, reduce cisplatin sensitivity in bladder cancer, implicating the potential therapeutic value of targeting this axis.

hsa_circ_0089552 (circ_NOTCH1)

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				[116]
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulation	Up regulation
Pathway Response	Notch signaling pathway			hsa04330
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
In-vitro Model	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
In-vivo Model	Thirty-two 6 week-old female nude mice divided into four groups (n = 8 per group) for injections of H1299 cells transfected with (a) pLKO.1 + pWPI, (b) shcircNOTCH1 + pWPI, (c) pLKO.1 + oeGPER and (d) shcircNOTCH1 + oeGPER.
Response Summary	GPER promotes non-small-cell lung cancer cell growth by regulating YAP1-TEAD/QKI/circNOTCH1/m6A methylated NOTCH1 signalling. Further exploration of the mechanism demonstrated that GPER could up-regulate hsa_circ_0089552 (circNOTCH1), which could compete with NOTCH1 mRNA for METTL14 binding.

AC026356.1

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		[117]
Responsed Disease	Lung adenocarcinoma [ICD-11: 2C25.0]
Target Regulation	Up regulation
In-vivo Model	Cells (2 × 10⁴) were seeded onto 12-well plates and cultured in serum-free 1640 medium. Cell spheroids were documented and quantified using an inverted microscope (Olympus, Japan) after two weeks.

Alpha-actinin-4 (ACTN4)

Target Gene

SARS-CoV-2 [ICD-11: XN109]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[118]
Responsed Disease	SARS-CoV-2 [ICD-11: XN109]

Alpha-synuclein (SNCA)

Target Gene

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				[119]
Responsed Disease	Parkinson disease [ICD-11: 8A00]
Target Regulation	Up regulation
In-vitro Model	SN4741	N.A.	Mus musculus	CVCL_S466
In-vivo Model	Male nude mice (6 weeks old) were purchased from the Shanghai Laboratory Animal Central (Shanghai, China). 95D cells (1 × 10⁷) transfected with sh-HNRNPA2B1 or sh-NC lentiviruses were injected subcutaneously into the right flanks of mice. After 8 weeks, the mice were sacrificed, and the xenografted tumors were collected for hematoxylin-eosin (HE) staining and IHC analysis.

Amino acid transporter heavy chain SLC3A2 (SLC3A2)

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		[120]
Responsed Disease	Lung cancer [ICD-11: 2C25]
Target Regulation	Down regulation

Ankyrin repeat domain-containing protein 22 (ANKRD22)

Target Gene

Nasopharyngeal carcinoma [ICD-11: 2B6B]

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	Nasopharyngeal carcinoma [ICD-11: 2B6B]
Target Regulation	Up regulation

Aspartyl/asparaginyl beta-hydroxylase (ASPH)

Target Gene

Atherosclerosis [ICD-11: BD40]

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	Atherosclerosis [ICD-11: BD40.Z]
Target Regulation	Up regulation
In-vitro Model	HUVEC-CS	N.A.	Homo sapiens	CVCL_0F27
In-vivo Model	The adenovirus-mediated silencing METTL14 (ad-sh-METTL14) or negative control vectors were designed and packaged by GenePharma (Shanghai, China). All mice (18 mice in each group) were euthanized at 20 weeks of age by injection of pentobarbital sodium (250 mg/kg).

BET1-like protein (BET1L)

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				[123]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
In-vitro Model	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	SW620	Colon adenocarcinoma	Homo sapiens	CVCL_0547
	LoVo	Colon adenocarcinoma	Homo sapiens	CVCL_0399
	DLD-1	Colon adenocarcinoma	Homo sapiens	CVCL_0248
	FHC	Normal	Homo sapiens	CVCL_3688
In-vivo Model	For subcutaneous xenotransplantation, 3- to 4-week-old male BALB/c nude mice were randomly divided into groups (8 mice per group) and injected in the back flank with 100 μL of 1.0 × 10⁷ suspended cells.

C-C motif chemokine 5 (CCL5)

Target Gene

Gestational diabetes mellitus [ICD-11: JA63]

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	Gestational diabetes mellitus [ICD-11: JA63]
Responsed Drug	Fentanyl		Approved	Drug Info
Target Regulation	Up regulation
In-vitro Model	HPDE6c7	Normal	Homo sapiens	CVCL_0P38
	Capan-1	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0237
	SW1990	Pancreatic adenocarcinoma	Homo sapiens	CVCL_1723
	CFPAC-1	Cystic fibrosis	Homo sapiens	CVCL_1119

Calcium-binding and coiled-coil domain-containing protein 1 (CALCOCO1)

Target Gene

Breast cancer [ICD-11: 2C60]

In total 2 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	Paclitaxel		Approved	Drug Info
In-vitro Model	HEK293T	Normal	Homo sapiens	CVCL_0063
In-vivo Model	The experimental mice were housed in an SPF-grade animal laboratory at a temperature of approximately 25 °C, a humidity range of 50%, and an average daylight duration of 12 h. BALB/C female mice at 5-7 weeks of age were taken and prepared for tumor-bearing. After the mice were sacrificed, their tissues were collected, weighed and immediately snap-frozen in liquid nitrogen.
Experiment 2 Reporting the m6A-centered Disease Response of This Target Gene				[89]
Responsed Disease	Breast cancer [ICD-11: 2C60]
Responsed Drug	STM2457		Investigative	Drug Info
In-vitro Model	HEK293T	Normal	Homo sapiens	CVCL_0063
In-vivo Model	The experimental mice were housed in an SPF-grade animal laboratory at a temperature of approximately 25 °C, a humidity range of 50%, and an average daylight duration of 12 h. BALB/C female mice at 5-7 weeks of age were taken and prepared for tumor-bearing. After the mice were sacrificed, their tissues were collected, weighed and immediately snap-frozen in liquid nitrogen.

Caldesmon (CALD1)

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		[125]
Responsed Disease	Oral squamous cell carcinoma [ICD-11: 2B6E.0]
Target Regulation	Up regulation

CCN family member 2 (CTGF)

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				[126]
Responsed Disease	Chronic kidney disease [ICD-11: GB61]
Target Regulation	Up regulation
In-vitro Model	SV40 MES 13	N.A.	Mus musculus	CVCL_5368
In-vitro Model	NRK-52E	Normal	Rattus norvegicus	CVCL_0468

Circ_FUT8

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				[127]
Responsed Disease	Liver cancer [ICD-11: 2C12]
Target Regulation	Up regulation
In-vitro Model	Huh-7	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0336
	HCCLM3	Adult hepatocellular carcinoma	Homo sapiens	CVCL_6832
	Hep 3B2.1-7	Childhood hepatocellular carcinoma	Homo sapiens	CVCL_0326
	MHCC97-H	Adult hepatocellular carcinoma	Homo sapiens	CVCL_4972
	THLE-3	Normal	Homo sapiens	CVCL_3804
In-vivo Model	Male BALb/c nude mice (three mice per group) were bought from Guangdong Medical Laboratory Animal Center, and indicated HCC cells were subcutaneously injected into the flanks of nude mice at 2 × 10⁶ cells per site.

Circ_GFR-Alpha-1

Target Gene

Female reproductive system disorders [ICD-11: SC4Y]

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	Female reproductive system disorders [ICD-11: SC4Y]
Pathway Response	Calcium signaling pathway			hsa04020
In-vitro Model	HEK293T	Normal	Homo sapiens	CVCL_0063
	FGSCs cell line (Female Germline Stem Cells)
Response Summary	Circ_GFR-Alpha-1 promotes female germline stem cells self-renewal by acting as a ceRNA that sponges miR-449, leading to enhanced GFRalpha-1 expression and activation of the GDNF signaling pathway. circGFRalpha-1 acts as a ceRNA based on METTL14-mediated cytoplasmic export through the GGACU motif.

Circ_ORC5

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				[45]
Responsed Disease	Gastric cancer [ICD-11: 2B72]
Target Regulation	Down regulation
In-vitro Model	SGC-7901	Gastric carcinoma	Homo sapiens	CVCL_0520
	MKN28	Gastric tubular adenocarcinoma	Homo sapiens	CVCL_1416
	MGC-803	Gastric mucinous adenocarcinoma	Homo sapiens	CVCL_5334
	GES-1	Normal	Homo sapiens	CVCL_EQ22
	BGC-823	Gastric carcinoma	Homo sapiens	CVCL_3360
	AGS	Gastric adenocarcinoma	Homo sapiens	CVCL_0139
Response Summary	METTL14-mediated m6A modification of Circ_ORC5 suppresses gastric cancer progression by regulating miR-30c-2-3p/AKT1S1 axis. METTL14 was downregulated in GC tissue samples and its low expression acted as a prognostic factor of poor survival in patients with GC.

Cyclic AMP-dependent transcription factor ATF-5 (ATF5)

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		[129]
Responsed Disease	Gastric cancer [ICD-11: 2B72]
Target Regulation	Down regulation

Dickkopf-related protein 3 (DKK3)

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				[130]
Responsed Disease	Diabetic nephropathy [ICD-11: GB61.Z]
In-vitro Model	HK-2 [Human kidney]	Normal	Homo sapiens	CVCL_0302
In-vivo Model	Female mice (8 weeks old, 20-25 g) on a C57BL/6J background were fasted for 12 h but were allowed to drink water freely. They were then injected intraperitoneally with 50 mg/kg body weight of freshly dissolved STZ in sterile PBS for four consecutive days. Mice were given sterile PBS alone in the same way as an untreated control. The mice's blood glucose levels were assessed two weeks after their most recent treatment. Mice that exhibited glucose levels greater than 200 mg/dL were classified as successful hyperglycemic models and were utilized in subsequent studies. Five months after the final dose of STZ, the mice were euthanized, and the renal tissues were collected for pathological examination to confirm the successful establishment of the model of diabetes nephropathy induced by hyperglycemia. All animal experiments were performed according to the guidelines of the Institutional Animal Care and Use Committee at the China Pharmaceutical University. Isoflurane was used to anesthetize mice.

Dynamin-1-like protein (DRP1)

Target Gene

Acute myocardial infarction [ICD-11: BA41]

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	Acute myocardial infarction [ICD-11: BA41]
Target Regulation	Up regulation

E3 ubiquitin-protein ligase UBR1 (UBR1)

Target Gene

Injuries of spine or trunk [ICD-11: ND51]

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	Spinal cord injury [ICD-11: ND51.2]
Target Regulation	Up regulation
In-vitro Model	PC-12	Lung papillary adenocarcinoma	Homo sapiens	CVCL_S979
In-vivo Model	After anesthetization with an intraperitoneal injection of ketamine (80 mg/kg) and xylazine (10 mg/kg), none of the rats had obvious abdominal distention, ascites, discomfort, or pain. Laminectomy was performed at T8-T10 (counting from top to bottom; from the 8th thoracic vertebra to the 10th thoracic vertebra). The spine was immobilized with a stereotaxic device, and the exposed spinal cord was severely injured at the center between T8 and T10 by a 5-g weight dropping freely from a height of 8 cm (Perot et al., 1987; Ray et al., 2000). After surgery, the rats were carefully nursed and fed and their urine was squeezed three times a day until reflex bladder emptying was established. Successful modeling was defined as (1) rapid retraction of the whole body, (2) rapid edema and congestion on the surface of the local spinal cord, (3) intact spinal dura mater, (4) flaccid paralysis of the hindlimbs, and (5) survival. Rats that underwent unsuccessful modeling were replaced. The SCI (1 d), SCI (7 d), and SCI (14 d) groups were killed on first, seventh, and 14th day after modeling, respectively, while the other groups were killed on the 14th day. Most operations in the sham group were the same as those in the SCI group, with no spinal cord contusions. The SCI + LV-NC, SCI + LV-UBR1, SCI + sh-NC, and SCI + sh-METTL14 groups were given lentiviral tail vein injections (once every 3 d, virus titers of 108 TU/ml; GenePharma) 3 d before SCI modeling.

Ferroptosis suppressor protein 1 (AIFM2)

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				[133]
Responsed Disease	Esophageal cancer [ICD-11: 2B70]
Responsed Drug	Cisplatin		Approved	Drug Info
In-vitro Model	TE-1	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1759
In-vitro Model	KYSE-150	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1348
In-vivo Model	The KYSE-150 cells were subcutaneously inoculated on the right side at a dosage of 10⁶ cells per mouse. After the tumor grew to approximately 50 mm3, mice were randomly divided into four groups (n = 6): Control, CisR-exo, Cis, and Cis + CisR-exo. Then, normal saline or cisplatin (20 mg/kg; twice a week) was intratumorally injected alone or combined with CisR-exos (10 μg; once every two days).

Frizzled-2 (FZD2)

Target Gene

Diabetic [ICD-11: 5A14]

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	Diabetic [ICD-11: 5A14]
In-vitro Model	CT26	Mouse colon adenocarcinoma	Mus musculus	CVCL_7254

Hamartin (TSC1)

Target Gene

Ulcerative colitis [ICD-11: DD71]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[135]
Responsed Disease	Ulcerative colitis [ICD-11: DD71]
Responsed Drug	Coptisine		Investigative	Drug Info
Target Regulation	Up regulation
In-vitro Model	RAW 264.7	Mouse leukemia	Mus musculus	CVCL_0493
In-vivo Model	Sixty mice were disposed in 6 groups randomly by using spss25.0 software after an adaption period of one week (n = 10): control, DSS model, 5-ASA (200 mg/kg) +DSS, coptisine 25 mg/kg + DSS (COP-l), coptisine 50 mg/kg + DSS (COP-M) and coptisine 100 mg/kg + DSS (COP-H). The dosages of 5-ASA and COP were implemented in accordance with the previous report.

Histone deacetylase 3 (HDAC3)

Target Gene

Acute ischemic stroke [ICD-11: 8B11]

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	Acute ischemic stroke [ICD-11: 8B11]
Target Regulation	Up regulation

HOX transcript antisense RNA (HOTAIR)

Target Gene

Disorders due to use of opioids [ICD-11: 6C43]

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	Disorders due to use of opioids [ICD-11: 6C43.1]
Responsed Drug	MM-102	Investigative	Drug Info
Target Regulation	Up regulation

hsa-mir-19a

Target Gene

Atherosclerosis [ICD-11: BD40]

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	Atherosclerosis [ICD-11: BD40.Z]
Target Regulation	Up regulation

Interleukin-12 subunit beta (IL12B)

Target Gene

Inflammatory response [ICD-11: MG46]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[138]
Responsed Disease	Inflammatory response [ICD-11: MG46]
Cell Process	RNA decay

Interleukin-13 (IL13)

Target Gene

Allergy [ICD-11: 4A8Z]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[139]
Responsed Disease	Allergy [ICD-11: 4A8Z]

Asthma [ICD-11: CA23]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[139]
Responsed Disease	Asthma [ICD-11: CA23]

Intraflagellar transport protein 80 homolog (IFT80)

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				[140]
Responsed Disease	Head and neck squamous carcinoma [ICD-11: 2B6E]
Target Regulation	Up regulation
In-vitro Model	HN4	Clear cell renal cell carcinoma	Homo sapiens	CVCL_IS30
	HN-6	Tongue squamous cell carcinoma	Homo sapiens	CVCL_8129
	WSU-HN30	Pharyngeal squamous cell carcinoma	Homo sapiens	CVCL_5525
	SCC-4	Tongue squamous cell carcinoma	Homo sapiens	CVCL_1684
	SCC-9	Tongue squamous cell carcinoma	Homo sapiens	CVCL_1685
	SCC-25	Tongue squamous cell carcinoma	Homo sapiens	CVCL_1682
	CAL-27	Tongue squamous cell carcinoma	Homo sapiens	CVCL_1107
In-vivo Model	To determine whether lnc-H2AFV-1 overexpression could enhance tumorigenicity in vivo, 1 × 10⁶ HN6 cells stably transduced with LV-lnc-H2AFV-1 or LV-NC were subcutaneously injected into the right and left flanks of six mice.

JmjC domain-containing protein 8 (JMJD8)

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				[141]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
In-vitro Model	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
In-vitro Model	SW620	Colon adenocarcinoma	Homo sapiens	CVCL_0547

Lnc_LSG1

Target Gene

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				[70]
Responsed Disease	Renal cell carcinoma of kidney [ICD-11: 2C90.0]
Target Regulation	Up regulation
Pathway Response	Ubiquitin mediated proteolysis			hsa04120
Cell Process	Ubiquitination
In-vitro Model	OS-RC-2	Clear cell renal cell carcinoma	Homo sapiens	CVCL_1626
	Caki-1	Clear cell renal cell carcinoma	Homo sapiens	CVCL_0234
	786-O	Renal cell carcinoma	Homo sapiens	CVCL_1051
In-vivo Model	For the xenograft tumor model, approximately 1 × 10⁶ ccRCC cells suspended in 100 uL PBS were subcutaneously inoculated in the right flank of 5-week-old BALB/c nude mice. For the ccRCC orthotopic implantation model, approximately 1 × 10⁶ ccRCC cells suspended in 30 uL Matrigel were injected under the renal capsule of 5-week-old BALB/c nude mice. After 6 weeks, the anesthetized mice were intraperitoneally injected with D-luciferin (Yeason) and imaged using an in vivo imaging system to detect tumor growth and metastasis. For the lung metastasis model, approximately 5 × 10⁵ ccRCC cells suspended in PBS were injected into the tail vein of 5-week-old mice. After 6-8 weeks, mice were anesthetized and lung metastasis was imaged as above.
Response Summary	The expression of METTL14 was negatively correlated to the prognosis, stage, and ccRCC tumor grade. Lnc-LSG1 could be regulated by METTL14. Lnc_LSG1 can directly bind to ESRP2 protein and promote ESRP2 degradation via facilitating ESRP2 ubiquitination.

long intergenic non-protein coding RNA 2747 (LINC02747)

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		[142]
Responsed Disease	Non-small cell lung cancer [ICD-11: 2C25.Y]
Target Regulation	Up regulation

long intergenic non-protein coding RNA 941 (LINC00941)

Target Gene

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				[143]
Responsed Disease	Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0]
Target Regulation	Up regulation
In-vitro Model	PANC-1	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0480
	MIA PaCa-2	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0428
	SW1990	Pancreatic adenocarcinoma	Homo sapiens	CVCL_1723
	AsPC-1	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0152
	BxPC-3	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0186
	HPDE6c7	Normal	Homo sapiens	CVCL_0P38
In-vivo Model	PANC-1 cells were stably transfected with LV-METTL14, LV-NC, sh-METTL14, sh-NC, or sh-LINC00941. A mixture of 2×10⁶ cells and 100 μL PBS was injected into the spleen of every BALB/c nude mouse. After two months of housing in a sterile environment, the mice were sacrificed. Their liver tissues were removed for hematoxylin and eosin (HE) staining.

Lysine-specific demethylase 6B (KDM6B)

Target Gene

Inflammatory response [ICD-11: MG46]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[144]
Responsed Disease	Inflammatory response [ICD-11: MG46]
Target Regulation	Down regulation
In-vitro Model	THP-1	Childhood acute monocytic leukemia	Homo sapiens	CVCL_0006
In-vitro Model	HEK293T	Normal	Homo sapiens	CVCL_0063

Macrophage colony-stimulating factor 1 receptor (CSF1R)

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				[145]
Responsed Disease	Non-small cell lung cancer [ICD-11: 2C25.Y]
Target Regulation	Up regulation
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
In-vitro Model	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060

miR-6858

Target Gene

Lichen planus [ICD-11: EA91]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[146]
Responsed Disease	Lichen planus [ICD-11: EA91.4]
Target Regulation	Up regulation

Mitochondrial fission 1 protein (FIS1)

Target Gene

Cognitive impairment [ICD-11: MB21]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[147]
Responsed Disease	Cognitive impairment [ICD-11: MB21]
Target Regulation	Up regulation
In-vitro Model	Neuro-2a	Mouse neuroblastoma	Mus musculus	CVCL_0470
In-vivo Model	To investigate chronic Cd-induced mitochondrial dysfunction and neurotoxicity in vivo, C57BL/6J mice were randomly assigned to 2 groups: (i) control group mice (n = 20) and (ii) Cd exposure group mice (n = 20).

Neurotrophic factor BDNF precursor form (BDNF)

Target Gene

Traumatic brain injury induced by controlled cortical impact injury [ICD-11: NA07]

In total 1 item(s) under this disease			Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene			[149]
Responsed Disease	Traumatic brain injury induced by controlled cortical impact injury [ICD-11: NA07]
Responsed Drug	Xuefu Zhuyu decoction	Investigative	Drug Info
Target Regulation	Up regulation
In-vivo Model	Adult male Sprague-Dawley rats (body weight 220 g-250 g) were acquired from Hunan Silaike Jingda Laboratory Animal Co., Ltd. (Changsha, China, license No. SCXK (XIANG) 2016-0002). They were housed under specific pathogen-free conditions in the Department of Laboratory Animals, Central South University (Changsha, China, license No. SYXK (XIANG) 2015-0017). All rats were kept in air-conditioned animal quarters under standard conditions (50 ± 10% relative humidity, 12-h light/dark cycle, 22 ± 2 °C), with ad libitum water and food.

Nicotinamide N-methyltransferase (NNMT)

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				[64]
Responsed Disease	Esophageal Squamous Cell Carcinoma [ICD-11: 2B70.1]
In-vitro Model	Eca-109	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_6898
In-vitro Model	KYSE-30	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1351

Nuclear factor of activated T-cells, cytoplasmic 1 (NFATC1)

Target Gene

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				[150]
Responsed Disease	Osteoporosis [ICD-11: FB83.1]
In-vitro Model	RAW 264.7	Mouse leukemia	Mus musculus	CVCL_0493
In-vitro Model	MC3T3-E1	Normal	Mus musculus	CVCL_0409

Paired box protein Pax-6 (PAX6)

Target Gene

Acute ischemic stroke [ICD-11: 8B11]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[151]
Responsed Disease	Acute ischemic stroke [ICD-11: 8B11]
In-vitro Model	BV-2	Normal	Mus musculus	CVCL_0182
In-vivo Model	C57BL/6 mice were anesthetized intraperitoneally with 1% sodium pentobarbital (100 mg/kg). The mouse was placed on a thermostatic blanket to maintain the rectal temperature at 37.0°C± 0.5°C during surgery. The left common carotid artery (CCA), external carotid artery (ECA), and internal carotid artery (ICA) were exposed through a midline incision in the cervico abdominal region. The CCA was ligated distally with surgical nylon monofilament.

Phosphoenolpyruvate carboxykinase [GTP], mitochondrial (PCK2)

Target Gene

Hepatic inflammation [ICD-11: DB97]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[152]
Responsed Disease	Hepatic inflammation [ICD-11: DB97]
Target Regulation	Up regulation

Phospholipid hydroperoxide glutathione peroxidase GPX4 (GPX4)

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				[153]
Responsed Disease	Small cell lung cancer [ICD-11: 2C25.1]
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	PC-9	Lung adenocarcinoma	Homo sapiens	CVCL_B260
	BEAS-2B	Normal	Homo sapiens	CVCL_0168
In-vivo Model	For xenograft establishment, six-week-old female athymic nude mice (n = 6 per group) were used, following ethical guidelines approved by the Institutional Animal Care and Use Committee. Each mouse received subcutaneous injections in the flank region with 1 × 10^6 cells suspended in 100 μL of serum-free medium, either sh-METTL3-transfected A549 cells or sh-NC-transfected controls. Tumour growth was monitored bi-dimensionally every week using callipers, with tumour volume calculated using the formula (length × width^2)/2. After 4 weeks, the mice were anaesthetised and euthanized by intraperitoneal injection of 3% pentobarbital sodium (100 mg/kg). The tumours were weighted and used for HE and Immunohistochemistry staining.

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		[154]
Responsed Disease	Osteoarthritis [ICD-11: FA05]
In-vivo Model	Female 8-week-old Wistar rats (weighed 200 ± 20 g) were housed under a 12-h light/dark cycle with temperature and humidity (23 ± 1°C and 52 ± 2%) maintained, and they had free access to food and tap water. After 1 week of adaptive feeding, rats were anesthetized by intraperitoneal injection of 40 mg/kg of sodium thiopental. A rat model of OA was established according to the reference.32 Iodoacetate causes joint pathology via the inhibition of glycolysis, thereby targeting the avascular cartilage and causing chondrocyte death.33 With the left leg flexed at a 90° angle at the knee, 2 mg of monosodium iodoacetate (Sigma-Aldrich, MO, USA) was injected through the patellar ligament between the tibia and the femur using a 26GX3/8 needle at a volume of 25 μL. Control rats received an intra-articular injection of sterile saline (25 μL) alone. After recovery, the animals were returned to cages. Seven days after injection, the cartilages in the control and OA groups were collected for gene expression analysis.

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		[155]
Responsed Disease	Osteoporosis [ICD-11: FB83.1]
Target Regulation	Up regulation

Polyamine-transporting ATPase 13A3 (ATP13A3)

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		[156]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulation	Up regulation
In-vitro Model	HCoEpiC (Healthy colon epithelial HCoEpiC cells)
In-vivo Model	The nude mice were randomly assigned to two groups consisting of six mice each. We injected transformed cells (P0 and P40) into the flank of each mouse in 0.1 mL of sterile PBS to form xenograft tumors. The tumor volume was measured every 2 or 3 days (volume = length × width2 × 1/2). The tumors were resected, imaged, and weighed after the mice were sacrificed. One piece of each tumor tissue was fixed in 4% (v/v) paraformaldehyde for hematoxylin and eosin (H&E) and immunohistochemistry (IHC) staining, and the remaining tissue was stored at -80 °C.

pri-miR-17

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				[157]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Responsed Drug	Fluorouracil		Approved	Drug Info
Target Regulation	Up regulation
In-vitro Model	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	LoVo	Colon adenocarcinoma	Homo sapiens	CVCL_0399
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
	SW620	Colon adenocarcinoma	Homo sapiens	CVCL_0547
	Caco-2	Colon adenocarcinoma	Homo sapiens	CVCL_0025
	HT29	Colon cancer	Mus musculus	CVCL_A8EZ
	RKO	Colon carcinoma	Homo sapiens	CVCL_0504
	FHC	Normal	Homo sapiens	CVCL_3688
	NCM460	Normal	Homo sapiens	CVCL_0460

Progestin and adipoQ receptor family member 3 (PAQR3)

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				[158]
Responsed Disease	Diabetic nephropathy [ICD-11: GB61.Z]
In-vitro Model	GEC	N.A.	Epinephelus tauvina	CVCL_S009
In-vitro Model	THP-1	Childhood acute monocytic leukemia	Homo sapiens	CVCL_0006

Protein disulfide-isomerase (P4HB)

Target Gene

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			[159]
Responsed Disease	Osteoporosis [ICD-11: FB83.1]
Responsed Drug	ICARIIN	Investigative	Drug Info
In-vivo Model	After anesthesia with ketamine-xylazine(intraperitoneal injection, 60 and 5 mg/kg, respectively), the rats were operated to remove the bilateral ovaries. For the rats in the Sham group, only the fat around the ovaries was surgically removed. Four weeks after the operation, the animals were orally treated with ICA (250 mg/kg) daily for 10 weeks .

Pseudorabies Virus (PRV)

Target Gene

Rabies [ICD-11: 1C82]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[160]
Responsed Disease	Rabies [ICD-11: 1C82]
Responsed Drug	3-deazidenosine		Investigative	Drug Info
Target Regulation	Up regulation
In-vitro Model	PK-15	N.A.	Sus scrofa	CVCL_2160

Receptor-interacting serine/threonine-protein kinase 3 (RIP3)

Target Gene

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		[161]
Responsed Disease	Abdominal aortic aneurysm [ICD-11: BD50.4]
Target Regulation	Up regulation

Retinoic Acid Receptor Alpha-Retinoic Acid Receptor Alpha (PML-RARalpha)

Target Gene

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		[101]
Responsed Disease	Blood malignancies [ICD-11: 2B33.Y]
Target Regulation	Up regulation
Cell Process	Cell differentiation

Rho GTPase-activating protein 12 (ARHGAP12)

Target Gene

Atherosclerosis [ICD-11: BD40]

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	Atherosclerosis [ICD-11: BD40.Z]
Target Regulation	Up regulation
In-vitro Model	HUVEC-CS	N.A.	Homo sapiens	CVCL_0F27
In-vivo Model	The adenovirus-mediated silencing METTL14 (ad-sh-METTL14) or negative control vectors were designed and packaged by GenePharma (Shanghai, China). All mice (18 mice in each group) were euthanized at 20 weeks of age by injection of pentobarbital sodium (250 mg/kg).

RNA-binding protein Nova-2 (NOVA2)

Target Gene

Hepatic fibrosis/cirrhosis [ICD-11: DB93]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[162]
Responsed Disease	Hepatic fibrosis/cirrhosis [ICD-11: DB93]
Target Regulation	Down regulation

SET-binding protein (SETBP1)

Target Gene

Myelodysplastic neoplasms [ICD-11: 2A4Z]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[163]
Responsed Disease	Myelodysplastic neoplasms [ICD-11: 2A4Z]
In-vivo Model	In the first in vivo experiment focused on investigating the role of METTL14 in MDS cell proliferation in vivo, the MDS-L-luc cells were transduced with the Dox-inducible shMETTL14 (shMETTL14_Tet-on). After treatment with 2 μg/mL puromycin for a duration of 4 days, a total of 2.5 × 10⁶ selected cells were injected via the tail vein into irradiated female NCG-M mice aged 8-10 weeks (GemPharmatech, China) to establish cell line-derived xenograft (CDX) models. On day 14 post transplantation, 20 mice were randomly assigned to two groups and treated with either Dox or vehicle. A total of 2 mg Dox was dissolved in water and administered by gastric lavage once a day. Five mice from each group underwent in vivo chemiluminescence imaging on day 14, 21, and 28 after receiving intraperitoneal injection of luciferin (Promega, USA). Their overall survival (OS) was also observed and documented. The remaining five mice from each group were utilized to assess the proportions of human CD45+cells in bone marrow and peripheral blood on day 28 through flow cytometry analysis.

Solute carrier family 2, facilitated glucose transporter member 3 (SLC2A3)

Target Gene

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				[164]
Responsed Disease	Osteoporosis [ICD-11: FB83.1]
In-vitro Model	MC3T3-E1	Normal	Mus musculus	CVCL_0409
In-vivo Model	Female C57BL/6 mice, aged eight weeks, were selected for the study. The mice were divided into three groups with six mice per group. After intramuscular anesthesia (xylazine 10 mg/kg, ketamine 100 mg/kg), two groups underwent bilateral ovariectomy (OVX), while the remaining group had a sham operation. Ovariectomized mice were administered weekly intratibial injections of Mettl14 overexpression adenovirus containing at a concentration of 109 plaque-forming unit per injection, for a duration of 8 weeks. The mice were humanely euthanized one week after the final injection, and their tibia were gathered for further analysis. This study was approved by the ethics committee of Tongji University (NO: TJBH00823101). All the experimental methods were carried out in accordance with the approved guidelines. All experimental procedures involving mice were carried out in strict accordance with the recommendations in the ARRIVE guidelines (Animal Research: Reporting of In Vivo Experiments).

Spindlin-2A (SPIN2A)

Target Gene

Vascular Calcification [ICD-11: BE2Y]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[165]
Responsed Disease	Vascular Calcification [ICD-11: BE2Y]
Target Regulation	Up regulation
Pathway Response	NF-kappa B signaling pathway			hsa04064
In-vitro Model	THP-1	Childhood acute monocytic leukemia	Homo sapiens	CVCL_0006
	RAW 264.7	Mouse leukemia	Mus musculus	CVCL_0493
	NCTC clone 929	N.A.	Mus musculus	CVCL_0462
	HEK293T	Normal	Homo sapiens	CVCL_0063

SREBF2 antisense RNA 1 (SREBF2-AS1)

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				[166]
Responsed Disease	Liver hepatocellular carcinoma [ICD-11: 2C12.02]
Responsed Drug	Sorafenib		Approved	Drug Info
Target Regulation	Up regulation
In-vitro Model	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
	SNU-398	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0077
	THLE-2	Normal	Homo sapiens	CVCL_3803
	Huh-7	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0336

Taurine up-regulated 1 protein (TUG1)

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				[167]
Responsed Disease	Diabetic nephropathy [ICD-11: GB61.Z]
In-vitro Model	HK2	Normal	Acipenser baerii	CVCL_YE28

TNF and HNRNPL related immunoregulatory long non-coding RNA (THRIL)

Target Gene

Injury of other or unspecified intrathoracic organs [ICD-11: NB32]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[168]
Responsed Disease	Injury of other or unspecified intrathoracic organs [ICD-11: NB32.3]
Responsed Drug	LPS		Investigative	Drug Info
Target Regulation	Up regulation
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023

Transcription factor SOX-6 (SOX6)

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		[169]
Responsed Disease	Intrahepatic cholangiocarcinoma [ICD-11: 2C12.10]
Target Regulation	Up regulation

Transcription factor SOX-9 (SOX9)

Target Gene

Rheumatoid arthritis [ICD-11: FA20]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[170]
Responsed Disease	Rheumatoid arthritis [ICD-11: FA20]

Transmembrane protein 127 (TMEM127)

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				[171]
Responsed Disease	Breast cancer [ICD-11: 2C60]
Responsed Drug	Rapamycin		Approved	Drug Info
Target Regulation	Up regulation
In-vitro Model	MDA-MB-231	Breast adenocarcinoma	Homo sapiens	CVCL_0062
	T-47D	Invasive breast carcinoma	Homo sapiens	CVCL_0553
	HEK293T	Normal	Homo sapiens	CVCL_0063
In-vivo Model	Approximately 1 × 10⁶ viable MDA-MB-231 breast cancer cells were resuspended in 1:1 ratio in 50 μl medium and 50 μl matrigel (Corning, 354234) and injected orthotopically into the fourth mammary fat pad of each mouse. After injection, tumor size was measured twice a week using an electronic caliper. Tumor volumes were calculated with the formula: volume = (L × W2)/2, where L is the tumor length and W is the tumor width measured in millimeters.

TRHDE antisense RNA 1 (TRHDE-AS1)

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				[172]
Responsed Disease	Prostate cancer [ICD-11: 2C82]
In-vitro Model	RWPE-1	Normal	Homo sapiens	CVCL_3791
	22Rv1	Prostate carcinoma	Homo sapiens	CVCL_1045
	DU145	Prostate carcinoma	Homo sapiens	CVCL_0105
	LNCaP	Prostate carcinoma	Homo sapiens	CVCL_0395

Ubiquitin carboxyl-terminal hydrolase 38 (USP38)

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				[173]
Responsed Disease	Bladder cancer [ICD-11: 2C94]
Target Regulation	Up regulation
In-vitro Model	SV-HUC-1	Normal	Homo sapiens	CVCL_3798
In-vivo Model	BALB/c nude mice were purchased from the Slac Laboratories (Shanghai, China) and randomly divided into two groups. The xenograft mouse model was generated via tail-vein injection of METTL14-expressing T24 cells (5 × 10⁵ cells per mouse) into experimental mice while those injected with pcDNA3.1 empty vector transfected cells as control.

Zinc finger protein PLAGL2 (PLAGL2)

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				[174]
Responsed Disease	Non-small cell lung cancer [ICD-11: 2C25.Y]
Target Regulation	Up regulation
Pathway Response	Wnt signaling pathway			hsa04310
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
In-vivo Model	Twenty BALB/c nude mice (4-6 weeks) were randomly assigned to sh-NC, sh-METTL14, sh-METTL14+oe-NC, and sh-METTL14+oe-PLAGL2, with 5 mice in each group. Mice were raised under sterile conditions of ambient room temperature of 26-28°C, the humidity of 40-60%, and alternating day and night for 10 h/14 h. The Mice were fed sterile food and water. After 1 week of adaptive feeding, A549 cells that transfected with sh-NC, sh-METTL14, oe-NC, and oe-PLAGL2 were subcutaneously injected. The cell concentration was 5 × 10⁶/mL, and 200 μL was injected.

Zinc finger protein RFP (TRIM27)

Target Gene

Psoriasis [ICD-11: EA90]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[175]
Responsed Disease	Psoriasis [ICD-11: EA90]
In-vitro Model	HaCaT	Normal	Homo sapiens	CVCL_0038

Zinc transporter ZIP9 (SLC39A9)

Target Gene

Periodontitis [ICD-11: DA0C]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[176]
Responsed Disease	Periodontitis [ICD-11: DA0C]
Target Regulation	Down regulation

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				[178]
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.

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		[179]
Responsed Disease	Neuroblastoma [ICD-11: 2A00.11]
Response Summary	Some SNPs in the METTL14 gene are associated with predisposition to neuroblastoma.

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				[180]
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.

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				[181]
Responsed Disease	Oral squamous cell carcinoma [ICD-11: 2B6E.0]
In-vitro Model	HOK	Normal	Hexagrammos otakii	CVCL_YE19
	HN-6	Tongue squamous cell carcinoma	Homo sapiens	CVCL_8129
	HN-5	Squamous cell carcinoma of the oral cavity	Homo sapiens	CVCL_8128
	HN-15	Squamous cell carcinoma of the oral cavity	Homo sapiens	CVCL_W297
Response Summary	METTL3 and METTL14 are overexpressed in OSCC tissues and in the HN6 OSCC cell line that promotes cell proliferation. Overexpressed METTL3 or METTL14 is found to be an independent prognostic factor for short overall survival in patients with OSCC.

Rectum cancer [ICD-11: 2B92]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[182]
Responsed Disease	Rectum cancer [ICD-11: 2B92]
Target Regulation	Down regulation
Pathway Response	Nucleotide excision repair	hsa03420
Cell Process	DNA repair
	Epithelial-mesenchymal transition
Response Summary	The m6A RNA methylation regulators, specifically YTHDC2 and METTL14, were significantly down-regulated and were potential prognostic biomarkers in rectal cancer.

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				[183]
Responsed Disease	Pancreatic cancer [ICD-11: 2C10]
Responsed Drug	Gemcitabine		Approved	Drug Info
In-vitro Model	PANC-1	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0480
	BxPC-3	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0186
	MIA PaCa-2	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0428
	Hs 766T	Pancreatic adenocarcinoma	Homo sapiens	CVCL_0334
	AsPC-1	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0152
	Capan-2	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0026
In-vivo Model	NOD/SCID mice (6-week-old) were injected (subcutaneously in both flanks) with 5.0 x 10⁶ PANC-1 GemR cells (infected with scr or METTL14 shRNA) per mouse suspended in 50 ul PBS and mixed with equal volume of growth factor reduced matrigel. One week after injection, we started measuring tumor size at the indicated times. Tumor size was calculated by 0.5 × (long diameter) × (short diameter)2. The mice were treated with vehicle or 100 mg/kg gemcitabine intraperitoneally twice a week.
Response Summary	Suppression of METTL14 obviously increased the sensitivity of gemcitabine in resistant cells. This study suggested that METTL14 is a potential target for chemotherapy resistance in pancreatic cancer.

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				[184]
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Pathway Response	PI3K-Akt signaling pathway			hsa04151
In-vitro Model	SK-MES-1	Lung squamous cell carcinoma	Homo sapiens	CVCL_0630
	NCI-H520	Lung squamous cell carcinoma	Homo sapiens	CVCL_1566
	NCI-H460	Lung large cell carcinoma	Homo sapiens	CVCL_0459
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	BEAS-2B	Normal	Homo sapiens	CVCL_0168
	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	16HBE14o-	Normal	Homo sapiens	CVCL_0112
Response Summary	Silencing of METTL14 suppressed non-small cell lung cancer malignancy by inhibiting Twist-mediated activation of AKT signaling.

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				[185]
Responsed Disease	Ovarian cancer [ICD-11: 2C73]
Cell Process	Cell apoptosis
In-vitro Model	CRL-11731D cell line (Human ovarian cancer cell)
	TOV-112D	Ovarian endometrioid adenocarcinoma	Homo sapiens	CVCL_3612
Response Summary	METTL3 can regulate m6A methylation independently of METTL14 and WTAP in endometrioid epithelial ovarian cancer.

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				[186]
Responsed Disease	Cervical cancer [ICD-11: 2C77]
Pathway Response	PI3K-Akt signaling pathway			hsa04151
Pathway Response	mTOR signaling pathway			hsa04150
In-vitro Model	SiHa	Cervical squamous cell carcinoma	Homo sapiens	CVCL_0032
In-vitro Model	C-33 A	Cervical squamous cell carcinoma	Homo sapiens	CVCL_1094
Response Summary	Up-regulation of METTL14 acted as an adverse prognostic factor for overall survival in cervical cancer patients. These study suggest an important oncogenic role of METTL14 in the growth and invasion of both HPV-positive and HPV-negative cervical cancer cells.

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		[187]
Responsed Disease	Renal cell carcinoma of kidney [ICD-11: 2C90.0]
Pathway Response	mTOR signaling pathway	hsa04150
	p53 signaling pathway	hsa04115
	PI3K-Akt signaling pathway	hsa04151
Cell Process	Adipogenesis
Response Summary	It is plausible that VHL-HIF-METTL3/14 pathways are involved in the m6A regulation in clear cell renal cell carcinoma cells, and PI3K-mTOR as well as p53 signaling pathways are possible downstream targets of m6A in ccRCC.

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				[188]
Responsed Disease	Bladder urothelial carcinoma [ICD-11: 2C94.2]
In-vitro Model	UM-UC-3	Bladder carcinoma	Homo sapiens	CVCL_1783
	TCCSUP	Bladder carcinoma	Homo sapiens	CVCL_1738
	T24	Bladder carcinoma	Homo sapiens	CVCL_0554
	SV-HUC-1	Normal	Homo sapiens	CVCL_3798
	RT-112	Bladder carcinoma	Homo sapiens	CVCL_1670
	MGH-U3	Bladder carcinoma	Homo sapiens	CVCL_9827
	J82	Bladder carcinoma	Homo sapiens	CVCL_0359
	5637	Bladder carcinoma	Homo sapiens	CVCL_0126
Response Summary	METTL14 as a key component for m6 A RNA deposit and that it is closely related to BlCa progression, playing an important role in tumor aggressiveness.

Hematological disorders [ICD-11: 3C0Z]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[189]
Responsed Disease	Hematological disorders [ICD-11: 3C0Z]
Response Summary	This reviewed summarize and discuss recent findings regarding the biological functions and underlying mechanisms of m6A modification(i.e., the METTL3/METTL14/WTAP complex and other cofactor proteins) and the associated machinery in normal hematopoiesis and the initiation, progression, and drug response of acute myeloid leukemia (AML), a major subtype of leukemia usually associated with unfavorable prognosis.

Lupus erythematosus [ICD-11: 4A40]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[190]
Responsed Disease	Lupus erythematosus [ICD-11: 4A40]
Response Summary	These findings suggested decreased YTHDF2 that was associated with disease activity play an important role in the pathogenesis of SLE, METTL14 and ALKBH5 were concomitantly decreased.

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				[191]
Responsed Disease	Obesity [ICD-11: 5B81]
Cell Process	Mitotic clonal expansion
In-vitro Model	3T3F442A	Normal	Mus musculus	CVCL_0122
	3T3-L1	Normal	Mus musculus	CVCL_0123
	COS (From the African green monkey cell line (CV-1).)
	MEF (Mouse embryonic fibroblasts)
In-vivo Model	Mice were anesthetized after 24 h of fasting, and 5 U of human insulin (Humalin R; Eli Lilly) was injected into the inferior vena cava. After 5 min, the liver and hind limb muscles were dissected and immediately frozen in liquid nitrogen.
Response Summary	WTAP, coupled with METTL3 and METTL14, is increased and distributed in nucleus by the induction of adipogenesis dependently on RNA in vitro Knockdown of each of these three proteins leads to cell cycle arrest and impaired adipogenesis associated with suppression of cyclin A2 upregulation during MCE, whose knockdown also impairs adipogenesis.

Glucose intolerance [ICD-11: 5C61]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[192]
Responsed Disease	Glucose Intolerance [ICD-11: 5C61.Y]
Responsed Drug	Tamoxifen		Approved	Drug Info
In-vitro Model	MIN6	Mouse insulinoma	Mus musculus	CVCL_0431
In-vivo Model	The mice were fed a normal chow diet (Harlan Teklad) and maintained in a standard 12-hour light/12-hour dark cycle. At the age of 10 weeks, both male and female mice were intraperitoneally injected with 250 L (20 mg/mL) tamoxifen every other day for three times to delete Mettl14 in Beta-cells. Intraperitoneal glucose tolerance tests were performed on mice at the age of 15 weeks after a 5-hour fast (2 g/kg dextrose). Insulin levels were measured at 0, 15, and 30 minutes after glucose challenge by using the Ultra Sensitive Mouse Insulin ELISA Kit .Insulin tolerance tests were performed after a 5-hour fast by administering human recombinant insulin (0.75 U/kg).
Response Summary	METTL14 deficiency in beta-cells induces glucose intolerance and a decrease in insulin secretion.To define the role of m6A in regulating the beta-cell function, the study generated beta-cell METTL14-specific knockout (beta-KO) mice by tamoxifen administration. beta-cell mass in beta-KO mice was related to beta-cell proliferation and also observed elevated mRNA and protein levels of Ire1-alpha and sXBP-1 in beta-KO islets.

Epilepsy due to structural or metabolic conditions or diseases [ICD-11: 8A60]

In total 1 item(s) under this disease			Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene			[193]
Responsed Disease	Epilepsy due to structural or metabolic conditions or diseases [ICD-11: 8A60.5]
Responsed Drug	Betaine	Approved	Drug Info
Target Regulation	Down regulation
In-vivo Model	Mice were treated with a single i.p. injection of pentylenetetrazol (PTZ, Sigma-Aldrich, P6500) at a dose of 50 mg/kg to establish the animal model of acute seizures [16]. Betaine (Sigma-Aldrich, B2629) was dissolved in normal saline, and administrated at a dose of 200 mg/kg or 600 mg/kg, i.p., to mice for 15 days before PTZ injection in reference to a previous study.

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		[194]
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.

Vascular Calcification [ICD-11: BE2Y]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[195]
Responsed Disease	Vascular Calcification [ICD-11: BE2Y]
In-vitro Model	HASMC cell line (Primary human artery smooth muscle cell)
In-vivo Model	The experimental rats received intraperitoneal injection with IS at a dosage of 100 mg/kg/48 h for 8,16,24 weeks. The control rats (n = 5) received same volume of phosphate-buffered saline injection every 48 h for 8,16,24 weeks.
Response Summary	METTL14 expression increases in calcific arteries and in HASMCs induced by indoxyl sulfate, thereby increasing the m6A level in RNA and decreasing the vascular repair function.METTL14 m6A regulates vascular calcification induced by indoxyl sulfate.

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			[196]
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).

Male infertility [ICD-11: GB04]

In total 2 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[197]
Responsed Disease	Male infertility [ICD-11: GB04]
Responsed Drug	Ethyl ester form of meclofenamic acid		Approved	Drug Info
Cell Process	Cell cycle
	Cell proliferation
In-vitro Model	GC-1 spg	Normal	Mus musculus	CVCL_8872
	HEK293T	Normal	Homo sapiens	CVCL_0063
In-vivo Model	Mouse GC-1 spg cells were treated with the ester form of meclofenamic acid (MA2) to inhibit the demethylase activity of FTO.
Response Summary	METTL3, METTL14, ALKBH5 and YTHDC2 are involved in the regulation of spermatogenesis and oogenesis. MA2 affected CDKs expression through the m6A-dependent mRNA degradation pathway, and thus repressed spermatogonial proliferation. Additionally, mutation of the predicted m6A sites in the Cdk2-3'UTR could mitigated the degradation of CDK2 mRNA after MA2 treatment.
Experiment 2 Reporting the m6A-centered Disease Response of This Target Gene				[198]
Responsed Disease	Male infertility [ICD-11: GB04]
In-vitro Model	Pachytene/diplotene spermatocyte (Prepared from undifferentiated mouse spermatogonial cells)
	Preleptotene spermatocyte (Prepared from undifferentiated mouse spermatogonial cells)
	Round spermatid. (Prepared from undifferentiated mouse spermatogonial cells)
	Type A1 spermatogonia (Prepared from undifferentiated mouse spermatogonial cells)
In-vivo Model	All mice described above were maintained on the C57BL/6J (B6) background. Mettl3- and Mettl14-floxed mice (Mettl3^flox/flox and Mettl14^flox/flox) were then bred with germ cell-specific expressed Cre mice including Vasa-Cre mouse line (Jackson Laboratory, Bar Harbor, Maine, USA) and Stra8-GFPCre mouse line for excising the loxP-flanked exon 4 and exon 2 to generate germ cell-specific Mettl3 and Mettl14KO mice, respectively. Germ cell-specific Mettl3 and Mettl14 double KO mice were obtained by crossing Mettl3^flox/floxMettl14^flox/flox with Mettl3^flox/+Mettl14^flox/+ or Mettl3^flox/+Mettl14^flox/flox carried germ cell-specific expressed Cre mice.
Response Summary	Combined deletion of Mettl3 and Mettl14 in advanced germ cells with Stra8-GFPCre disrupts spermiogenesis, whereas mice with single deletion of either Mettl3 or Mettl14 in advanced germ cells show normal spermatogenesis.

Inflammatory response [ICD-11: MG46]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[144]
Responsed Disease	Inflammatory response [ICD-11: MG46]
In-vitro Model	THP-1	Childhood acute monocytic leukemia	Homo sapiens	CVCL_0006
In-vitro Model	HEK293T	Normal	Homo sapiens	CVCL_0063

Catenin beta-1 (CTNNB1/Beta-catenin)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL14*
Cell Line	BMDM	Mus musculus
Treatment: METTL14 knockout mice BMDM Control: Wild type mice BMDM		GSE153512
Regulation		logFC: -6.10E-01 p-value: 2.52E-16
More Results	Click to View More RNA-seq Results

Pertuzumab [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[8]
Responsed Disease	Breast cancer		ICD-11: 2C60	Disease Info
Target Regulation	Down regulation
Pathway Response	Wnt signaling pathway			hsa04310
Cell Process	Glutathione synthesis
In-vitro Model	ZR-75-1	Invasive breast carcinoma	Homo sapiens	CVCL_0588
	T-47D	Invasive breast carcinoma	Homo sapiens	CVCL_0553
	SUM-159 (A mesenchymal triple-negative breast cancer cell line)
	SK-BR-3	Breast adenocarcinoma	Homo sapiens	CVCL_0033
	MDA-MB-468	Breast adenocarcinoma	Homo sapiens	CVCL_0419
	MDA-MB-453	Breast adenocarcinoma	Homo sapiens	CVCL_0418
	MDA-MB-361	Breast adenocarcinoma	Homo sapiens	CVCL_0620
	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
	HEK293T	Normal	Homo sapiens	CVCL_0063
	BT-549	Invasive breast carcinoma	Homo sapiens	CVCL_1092
	BT-474	Invasive breast carcinoma	Homo sapiens	CVCL_0179
	AU565	Breast adenocarcinoma	Homo sapiens	CVCL_1074
In-vivo Model	Luciferase-labeled rSKBR3 and MDA-MB-361 cells (1 × 10⁷ cells) mixed with 1:1 Matrigel (Corning, 356237) were subcutaneously injected into the fat pads of mice. After a tumor was palpable, the mice were randomized into four groups (five mice per group), and they were treated with vehicle, trastuzumab (20 mg/kg, intraperitoneal administration), roblitinib (30 mg/kg, oral administration), or a combination of both drugs.
Response Summary	m6A-hypomethylation regulated FGFR4 phosphorylates GSK-3beta and activates Catenin beta-1 (CTNNB1/Beta-catenin)/TCF4-SLC7A11/FPN1 signaling to drive anti-HER2 resistance. Knockdown of METTL14 significantly increased the expression level of FGFR4 in HER2-positive breast cancer cells. FGFR4 reduced the sensitivity of HER2-positive breast cancer to trastuzumab plus pertuzumab or tucatinib. These results pinpoint a mechanism of anti-HER2 resistance and provide a strategy for overcoming resistance via FGFR4 inhibition in recalcitrant HER2-positive breast cancer.

Trastuzumab [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[8]
Responsed Disease	Breast cancer		ICD-11: 2C60	Disease Info
Target Regulation	Down regulation
Pathway Response	Wnt signaling pathway			hsa04310
Cell Process	Glutathione synthesis
In-vitro Model	ZR-75-1	Invasive breast carcinoma	Homo sapiens	CVCL_0588
	T-47D	Invasive breast carcinoma	Homo sapiens	CVCL_0553
	SUM-159 (A mesenchymal triple-negative breast cancer cell line)
	SK-BR-3	Breast adenocarcinoma	Homo sapiens	CVCL_0033
	MDA-MB-468	Breast adenocarcinoma	Homo sapiens	CVCL_0419
	MDA-MB-453	Breast adenocarcinoma	Homo sapiens	CVCL_0418
	MDA-MB-361	Breast adenocarcinoma	Homo sapiens	CVCL_0620
	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
	HEK293T	Normal	Homo sapiens	CVCL_0063
	BT-549	Invasive breast carcinoma	Homo sapiens	CVCL_1092
	BT-474	Invasive breast carcinoma	Homo sapiens	CVCL_0179
	AU565	Breast adenocarcinoma	Homo sapiens	CVCL_1074
In-vivo Model	Luciferase-labeled rSKBR3 and MDA-MB-361 cells (1 × 10⁷ cells) mixed with 1:1 Matrigel (Corning, 356237) were subcutaneously injected into the fat pads of mice. After a tumor was palpable, the mice were randomized into four groups (five mice per group), and they were treated with vehicle, trastuzumab (20 mg/kg, intraperitoneal administration), roblitinib (30 mg/kg, oral administration), or a combination of both drugs.
Response Summary	m6A-hypomethylation regulated FGFR4 phosphorylates GSK-3beta and activates Catenin beta-1 (CTNNB1/Beta-catenin)/TCF4-SLC7A11/FPN1 signaling to drive anti-HER2 resistance. Knockdown of METTL14 significantly increased the expression level of FGFR4 in HER2-positive breast cancer cells. FGFR4 reduced the sensitivity of HER2-positive breast cancer to trastuzumab plus pertuzumab or tucatinib. These results pinpoint a mechanism of anti-HER2 resistance and provide a strategy for overcoming resistance via FGFR4 inhibition in recalcitrant HER2-positive breast cancer.

Tucatinib [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[8]
Responsed Disease	Breast cancer		ICD-11: 2C60	Disease Info
Target Regulation	Down regulation
Pathway Response	Wnt signaling pathway			hsa04310
Cell Process	Glutathione synthesis
In-vitro Model	ZR-75-1	Invasive breast carcinoma	Homo sapiens	CVCL_0588
	T-47D	Invasive breast carcinoma	Homo sapiens	CVCL_0553
	SUM-159 (A mesenchymal triple-negative breast cancer cell line)
	SK-BR-3	Breast adenocarcinoma	Homo sapiens	CVCL_0033
	MDA-MB-468	Breast adenocarcinoma	Homo sapiens	CVCL_0419
	MDA-MB-453	Breast adenocarcinoma	Homo sapiens	CVCL_0418
	MDA-MB-361	Breast adenocarcinoma	Homo sapiens	CVCL_0620
	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
	HEK293T	Normal	Homo sapiens	CVCL_0063
	BT-549	Invasive breast carcinoma	Homo sapiens	CVCL_1092
	BT-474	Invasive breast carcinoma	Homo sapiens	CVCL_0179
	AU565	Breast adenocarcinoma	Homo sapiens	CVCL_1074
In-vivo Model	Luciferase-labeled rSKBR3 and MDA-MB-361 cells (1 × 10⁷ cells) mixed with 1:1 Matrigel (Corning, 356237) were subcutaneously injected into the fat pads of mice. After a tumor was palpable, the mice were randomized into four groups (five mice per group), and they were treated with vehicle, trastuzumab (20 mg/kg, intraperitoneal administration), roblitinib (30 mg/kg, oral administration), or a combination of both drugs.
Response Summary	m6A-hypomethylation regulated FGFR4 phosphorylates GSK-3beta and activates Catenin beta-1 (CTNNB1/Beta-catenin)/TCF4-SLC7A11/FPN1 signaling to drive anti-HER2 resistance. Knockdown of METTL14 significantly increased the expression level of FGFR4 in HER2-positive breast cancer cells. FGFR4 reduced the sensitivity of HER2-positive breast cancer to trastuzumab plus pertuzumab or tucatinib. These results pinpoint a mechanism of anti-HER2 resistance and provide a strategy for overcoming resistance via FGFR4 inhibition in recalcitrant HER2-positive breast cancer.

Cystine/glutamate transporter (SLC7A11)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL14*
Cell Line	HepG2 cell line	Homo sapiens
Treatment: shMETTL14 HepG2 cells Control: shCtrl HepG2 cells		GSE121949
Regulation		logFC: -1.11E+00 p-value: 3.96E-11
More Results	Click to View More RNA-seq Results

Pertuzumab [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[8]
Responsed Disease	Breast cancer		ICD-11: 2C60	Disease Info
Target Regulation	Down regulation
Pathway Response	Wnt signaling pathway			hsa04310
Cell Process	Glutathione synthesis
In-vitro Model	ZR-75-1	Invasive breast carcinoma	Homo sapiens	CVCL_0588
	T-47D	Invasive breast carcinoma	Homo sapiens	CVCL_0553
	SUM-159 (A mesenchymal triple-negative breast cancer cell line)
	SK-BR-3	Breast adenocarcinoma	Homo sapiens	CVCL_0033
	MDA-MB-468	Breast adenocarcinoma	Homo sapiens	CVCL_0419
	MDA-MB-453	Breast adenocarcinoma	Homo sapiens	CVCL_0418
	MDA-MB-361	Breast adenocarcinoma	Homo sapiens	CVCL_0620
	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
	HEK293T	Normal	Homo sapiens	CVCL_0063
	BT-549	Invasive breast carcinoma	Homo sapiens	CVCL_1092
	BT-474	Invasive breast carcinoma	Homo sapiens	CVCL_0179
	AU565	Breast adenocarcinoma	Homo sapiens	CVCL_1074
In-vivo Model	Luciferase-labeled rSKBR3 and MDA-MB-361 cells (1 × 10⁷ cells) mixed with 1:1 Matrigel (Corning, 356237) were subcutaneously injected into the fat pads of mice. After a tumor was palpable, the mice were randomized into four groups (five mice per group), and they were treated with vehicle, trastuzumab (20 mg/kg, intraperitoneal administration), roblitinib (30 mg/kg, oral administration), or a combination of both drugs.
Response Summary	m6A-hypomethylation regulated FGFR4 phosphorylates GSK-3beta and activates beta-catenin/TCF4-Cystine/glutamate transporter (SLC7A11)/FPN1 signaling to drive anti-HER2 resistance. Knockdown of METTL14 significantly increased the expression level of FGFR4 in HER2-positive breast cancer cells. FGFR4 reduced the sensitivity of HER2-positive breast cancer to trastuzumab plus pertuzumab or tucatinib. These results pinpoint a mechanism of anti-HER2 resistance and provide a strategy for overcoming resistance via FGFR4 inhibition in recalcitrant HER2-positive breast cancer.

Trastuzumab [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[8]
Responsed Disease	Breast cancer		ICD-11: 2C60	Disease Info
Target Regulation	Down regulation
Pathway Response	Wnt signaling pathway			hsa04310
Cell Process	Glutathione synthesis
In-vitro Model	ZR-75-1	Invasive breast carcinoma	Homo sapiens	CVCL_0588
	T-47D	Invasive breast carcinoma	Homo sapiens	CVCL_0553
	SUM-159 (A mesenchymal triple-negative breast cancer cell line)
	SK-BR-3	Breast adenocarcinoma	Homo sapiens	CVCL_0033
	MDA-MB-468	Breast adenocarcinoma	Homo sapiens	CVCL_0419
	MDA-MB-453	Breast adenocarcinoma	Homo sapiens	CVCL_0418
	MDA-MB-361	Breast adenocarcinoma	Homo sapiens	CVCL_0620
	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
	HEK293T	Normal	Homo sapiens	CVCL_0063
	BT-549	Invasive breast carcinoma	Homo sapiens	CVCL_1092
	BT-474	Invasive breast carcinoma	Homo sapiens	CVCL_0179
	AU565	Breast adenocarcinoma	Homo sapiens	CVCL_1074
In-vivo Model	Luciferase-labeled rSKBR3 and MDA-MB-361 cells (1 × 10⁷ cells) mixed with 1:1 Matrigel (Corning, 356237) were subcutaneously injected into the fat pads of mice. After a tumor was palpable, the mice were randomized into four groups (five mice per group), and they were treated with vehicle, trastuzumab (20 mg/kg, intraperitoneal administration), roblitinib (30 mg/kg, oral administration), or a combination of both drugs.
Response Summary	m6A-hypomethylation regulated FGFR4 phosphorylates GSK-3beta and activates beta-catenin/TCF4-Cystine/glutamate transporter (SLC7A11)/FPN1 signaling to drive anti-HER2 resistance. Knockdown of METTL14 significantly increased the expression level of FGFR4 in HER2-positive breast cancer cells. FGFR4 reduced the sensitivity of HER2-positive breast cancer to trastuzumab plus pertuzumab or tucatinib. These results pinpoint a mechanism of anti-HER2 resistance and provide a strategy for overcoming resistance via FGFR4 inhibition in recalcitrant HER2-positive breast cancer.

Tucatinib [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[8]
Responsed Disease	Breast cancer		ICD-11: 2C60	Disease Info
Target Regulation	Down regulation
Pathway Response	Wnt signaling pathway			hsa04310
Cell Process	Glutathione synthesis
In-vitro Model	ZR-75-1	Invasive breast carcinoma	Homo sapiens	CVCL_0588
	T-47D	Invasive breast carcinoma	Homo sapiens	CVCL_0553
	SUM-159 (A mesenchymal triple-negative breast cancer cell line)
	SK-BR-3	Breast adenocarcinoma	Homo sapiens	CVCL_0033
	MDA-MB-468	Breast adenocarcinoma	Homo sapiens	CVCL_0419
	MDA-MB-453	Breast adenocarcinoma	Homo sapiens	CVCL_0418
	MDA-MB-361	Breast adenocarcinoma	Homo sapiens	CVCL_0620
	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
	HEK293T	Normal	Homo sapiens	CVCL_0063
	BT-549	Invasive breast carcinoma	Homo sapiens	CVCL_1092
	BT-474	Invasive breast carcinoma	Homo sapiens	CVCL_0179
	AU565	Breast adenocarcinoma	Homo sapiens	CVCL_1074
In-vivo Model	Luciferase-labeled rSKBR3 and MDA-MB-361 cells (1 × 10⁷ cells) mixed with 1:1 Matrigel (Corning, 356237) were subcutaneously injected into the fat pads of mice. After a tumor was palpable, the mice were randomized into four groups (five mice per group), and they were treated with vehicle, trastuzumab (20 mg/kg, intraperitoneal administration), roblitinib (30 mg/kg, oral administration), or a combination of both drugs.
Response Summary	m6A-hypomethylation regulated FGFR4 phosphorylates GSK-3beta and activates beta-catenin/TCF4-Cystine/glutamate transporter (SLC7A11)/FPN1 signaling to drive anti-HER2 resistance. Knockdown of METTL14 significantly increased the expression level of FGFR4 in HER2-positive breast cancer cells. FGFR4 reduced the sensitivity of HER2-positive breast cancer to trastuzumab plus pertuzumab or tucatinib. These results pinpoint a mechanism of anti-HER2 resistance and provide a strategy for overcoming resistance via FGFR4 inhibition in recalcitrant HER2-positive breast cancer.

Fibroblast growth factor receptor 4 (FGFR4)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL14*
Cell Line	HepG2 cell line	Homo sapiens
Treatment: shMETTL14 HepG2 cells Control: shCtrl HepG2 cells		GSE121949
Regulation		logFC: -7.17E-01 p-value: 3.71E-06
More Results	Click to View More RNA-seq Results

Pertuzumab [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[8]
Responsed Disease	Breast cancer		ICD-11: 2C60	Disease Info
Target Regulation	Down regulation
Pathway Response	Wnt signaling pathway			hsa04310
Cell Process	Glutathione synthesis
In-vitro Model	ZR-75-1	Invasive breast carcinoma	Homo sapiens	CVCL_0588
	T-47D	Invasive breast carcinoma	Homo sapiens	CVCL_0553
	SUM-159 (A mesenchymal triple-negative breast cancer cell line)
	SK-BR-3	Breast adenocarcinoma	Homo sapiens	CVCL_0033
	MDA-MB-468	Breast adenocarcinoma	Homo sapiens	CVCL_0419
	MDA-MB-453	Breast adenocarcinoma	Homo sapiens	CVCL_0418
	MDA-MB-361	Breast adenocarcinoma	Homo sapiens	CVCL_0620
	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
	HEK293T	Normal	Homo sapiens	CVCL_0063
	BT-549	Invasive breast carcinoma	Homo sapiens	CVCL_1092
	BT-474	Invasive breast carcinoma	Homo sapiens	CVCL_0179
	AU565	Breast adenocarcinoma	Homo sapiens	CVCL_1074
In-vivo Model	Luciferase-labeled rSKBR3 and MDA-MB-361 cells (1 × 10⁷ cells) mixed with 1:1 Matrigel (Corning, 356237) were subcutaneously injected into the fat pads of mice. After a tumor was palpable, the mice were randomized into four groups (five mice per group), and they were treated with vehicle, trastuzumab (20 mg/kg, intraperitoneal administration), roblitinib (30 mg/kg, oral administration), or a combination of both drugs.
Response Summary	m6A-hypomethylation regulated Fibroblast growth factor receptor 4 (FGFR4) phosphorylates GSK-3beta and activates beta-catenin/TCF4-SLC7A11/FPN1 signaling to drive anti-HER2 resistance. Knockdown of METTL14 significantly increased the expression level of FGFR4 in HER2-positive breast cancer cells. FGFR4 reduced the sensitivity of HER2-positive breast cancer to trastuzumab plus pertuzumab or tucatinib. These results pinpoint a mechanism of anti-HER2 resistance and provide a strategy for overcoming resistance via FGFR4 inhibition in recalcitrant HER2-positive breast cancer.

Trastuzumab [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[8]
Responsed Disease	Breast cancer		ICD-11: 2C60	Disease Info
Target Regulation	Down regulation
Pathway Response	Wnt signaling pathway			hsa04310
Cell Process	Glutathione synthesis
In-vitro Model	ZR-75-1	Invasive breast carcinoma	Homo sapiens	CVCL_0588
	T-47D	Invasive breast carcinoma	Homo sapiens	CVCL_0553
	SUM-159 (A mesenchymal triple-negative breast cancer cell line)
	SK-BR-3	Breast adenocarcinoma	Homo sapiens	CVCL_0033
	MDA-MB-468	Breast adenocarcinoma	Homo sapiens	CVCL_0419
	MDA-MB-453	Breast adenocarcinoma	Homo sapiens	CVCL_0418
	MDA-MB-361	Breast adenocarcinoma	Homo sapiens	CVCL_0620
	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
	HEK293T	Normal	Homo sapiens	CVCL_0063
	BT-549	Invasive breast carcinoma	Homo sapiens	CVCL_1092
	BT-474	Invasive breast carcinoma	Homo sapiens	CVCL_0179
	AU565	Breast adenocarcinoma	Homo sapiens	CVCL_1074
In-vivo Model	Luciferase-labeled rSKBR3 and MDA-MB-361 cells (1 × 10⁷ cells) mixed with 1:1 Matrigel (Corning, 356237) were subcutaneously injected into the fat pads of mice. After a tumor was palpable, the mice were randomized into four groups (five mice per group), and they were treated with vehicle, trastuzumab (20 mg/kg, intraperitoneal administration), roblitinib (30 mg/kg, oral administration), or a combination of both drugs.
Response Summary	m6A-hypomethylation regulated Fibroblast growth factor receptor 4 (FGFR4) phosphorylates GSK-3beta and activates beta-catenin/TCF4-SLC7A11/FPN1 signaling to drive anti-HER2 resistance. Knockdown of METTL14 significantly increased the expression level of FGFR4 in HER2-positive breast cancer cells. FGFR4 reduced the sensitivity of HER2-positive breast cancer to trastuzumab plus pertuzumab or tucatinib. These results pinpoint a mechanism of anti-HER2 resistance and provide a strategy for overcoming resistance via FGFR4 inhibition in recalcitrant HER2-positive breast cancer.

Tucatinib [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[8]
Responsed Disease	Breast cancer		ICD-11: 2C60	Disease Info
Target Regulation	Down regulation
Pathway Response	Wnt signaling pathway			hsa04310
Cell Process	Glutathione synthesis
In-vitro Model	ZR-75-1	Invasive breast carcinoma	Homo sapiens	CVCL_0588
	T-47D	Invasive breast carcinoma	Homo sapiens	CVCL_0553
	SUM-159 (A mesenchymal triple-negative breast cancer cell line)
	SK-BR-3	Breast adenocarcinoma	Homo sapiens	CVCL_0033
	MDA-MB-468	Breast adenocarcinoma	Homo sapiens	CVCL_0419
	MDA-MB-453	Breast adenocarcinoma	Homo sapiens	CVCL_0418
	MDA-MB-361	Breast adenocarcinoma	Homo sapiens	CVCL_0620
	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
	HEK293T	Normal	Homo sapiens	CVCL_0063
	BT-549	Invasive breast carcinoma	Homo sapiens	CVCL_1092
	BT-474	Invasive breast carcinoma	Homo sapiens	CVCL_0179
	AU565	Breast adenocarcinoma	Homo sapiens	CVCL_1074
In-vivo Model	Luciferase-labeled rSKBR3 and MDA-MB-361 cells (1 × 10⁷ cells) mixed with 1:1 Matrigel (Corning, 356237) were subcutaneously injected into the fat pads of mice. After a tumor was palpable, the mice were randomized into four groups (five mice per group), and they were treated with vehicle, trastuzumab (20 mg/kg, intraperitoneal administration), roblitinib (30 mg/kg, oral administration), or a combination of both drugs.
Response Summary	m6A-hypomethylation regulated Fibroblast growth factor receptor 4 (FGFR4) phosphorylates GSK-3beta and activates beta-catenin/TCF4-SLC7A11/FPN1 signaling to drive anti-HER2 resistance. Knockdown of METTL14 significantly increased the expression level of FGFR4 in HER2-positive breast cancer cells. FGFR4 reduced the sensitivity of HER2-positive breast cancer to trastuzumab plus pertuzumab or tucatinib. These results pinpoint a mechanism of anti-HER2 resistance and provide a strategy for overcoming resistance via FGFR4 inhibition in recalcitrant HER2-positive breast cancer.

Glycogen synthase kinase-3 beta (GSK3Beta/GSK3B)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL14*
Cell Line	BMDM	Mus musculus
Treatment: METTL14 knockout mice BMDM Control: Wild type mice BMDM		GSE153512
Regulation		logFC: 1.08E+00 p-value: 1.69E-24
More Results	Click to View More RNA-seq Results

Pertuzumab [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[8]
Responsed Disease	Breast cancer		ICD-11: 2C60	Disease Info
Target Regulation	Down regulation
Pathway Response	Wnt signaling pathway			hsa04310
Cell Process	Glutathione synthesis
In-vitro Model	ZR-75-1	Invasive breast carcinoma	Homo sapiens	CVCL_0588
	T-47D	Invasive breast carcinoma	Homo sapiens	CVCL_0553
	SUM-159 (A mesenchymal triple-negative breast cancer cell line)
	SK-BR-3	Breast adenocarcinoma	Homo sapiens	CVCL_0033
	MDA-MB-468	Breast adenocarcinoma	Homo sapiens	CVCL_0419
	MDA-MB-453	Breast adenocarcinoma	Homo sapiens	CVCL_0418
	MDA-MB-361	Breast adenocarcinoma	Homo sapiens	CVCL_0620
	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
	HEK293T	Normal	Homo sapiens	CVCL_0063
	BT-549	Invasive breast carcinoma	Homo sapiens	CVCL_1092
	BT-474	Invasive breast carcinoma	Homo sapiens	CVCL_0179
	AU565	Breast adenocarcinoma	Homo sapiens	CVCL_1074
In-vivo Model	Luciferase-labeled rSKBR3 and MDA-MB-361 cells (1 × 10⁷ cells) mixed with 1:1 Matrigel (Corning, 356237) were subcutaneously injected into the fat pads of mice. After a tumor was palpable, the mice were randomized into four groups (five mice per group), and they were treated with vehicle, trastuzumab (20 mg/kg, intraperitoneal administration), roblitinib (30 mg/kg, oral administration), or a combination of both drugs.
Response Summary	m6A-hypomethylation regulated FGFR4 phosphorylates Glycogen synthase kinase-3 beta (GSK3Beta/GSK3B) and activates beta-catenin/TCF4-SLC7A11/FPN1 signaling to drive anti-HER2 resistance. Knockdown of METTL14 significantly increased the expression level of FGFR4 in HER2-positive breast cancer cells. FGFR4 reduced the sensitivity of HER2-positive breast cancer to trastuzumab plus pertuzumab or tucatinib. These results pinpoint a mechanism of anti-HER2 resistance and provide a strategy for overcoming resistance via FGFR4 inhibition in recalcitrant HER2-positive breast cancer.

Trastuzumab [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[8]
Responsed Disease	Breast cancer		ICD-11: 2C60	Disease Info
Target Regulation	Down regulation
Pathway Response	Wnt signaling pathway			hsa04310
Cell Process	Glutathione synthesis
In-vitro Model	ZR-75-1	Invasive breast carcinoma	Homo sapiens	CVCL_0588
	T-47D	Invasive breast carcinoma	Homo sapiens	CVCL_0553
	SUM-159 (A mesenchymal triple-negative breast cancer cell line)
	SK-BR-3	Breast adenocarcinoma	Homo sapiens	CVCL_0033
	MDA-MB-468	Breast adenocarcinoma	Homo sapiens	CVCL_0419
	MDA-MB-453	Breast adenocarcinoma	Homo sapiens	CVCL_0418
	MDA-MB-361	Breast adenocarcinoma	Homo sapiens	CVCL_0620
	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
	HEK293T	Normal	Homo sapiens	CVCL_0063
	BT-549	Invasive breast carcinoma	Homo sapiens	CVCL_1092
	BT-474	Invasive breast carcinoma	Homo sapiens	CVCL_0179
	AU565	Breast adenocarcinoma	Homo sapiens	CVCL_1074
In-vivo Model	Luciferase-labeled rSKBR3 and MDA-MB-361 cells (1 × 10⁷ cells) mixed with 1:1 Matrigel (Corning, 356237) were subcutaneously injected into the fat pads of mice. After a tumor was palpable, the mice were randomized into four groups (five mice per group), and they were treated with vehicle, trastuzumab (20 mg/kg, intraperitoneal administration), roblitinib (30 mg/kg, oral administration), or a combination of both drugs.
Response Summary	m6A-hypomethylation regulated FGFR4 phosphorylates Glycogen synthase kinase-3 beta (GSK3Beta/GSK3B) and activates beta-catenin/TCF4-SLC7A11/FPN1 signaling to drive anti-HER2 resistance. Knockdown of METTL14 significantly increased the expression level of FGFR4 in HER2-positive breast cancer cells. FGFR4 reduced the sensitivity of HER2-positive breast cancer to trastuzumab plus pertuzumab or tucatinib. These results pinpoint a mechanism of anti-HER2 resistance and provide a strategy for overcoming resistance via FGFR4 inhibition in recalcitrant HER2-positive breast cancer.

Tucatinib [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[8]
Responsed Disease	Breast cancer		ICD-11: 2C60	Disease Info
Target Regulation	Down regulation
Pathway Response	Wnt signaling pathway			hsa04310
Cell Process	Glutathione synthesis
In-vitro Model	ZR-75-1	Invasive breast carcinoma	Homo sapiens	CVCL_0588
	T-47D	Invasive breast carcinoma	Homo sapiens	CVCL_0553
	SUM-159 (A mesenchymal triple-negative breast cancer cell line)
	SK-BR-3	Breast adenocarcinoma	Homo sapiens	CVCL_0033
	MDA-MB-468	Breast adenocarcinoma	Homo sapiens	CVCL_0419
	MDA-MB-453	Breast adenocarcinoma	Homo sapiens	CVCL_0418
	MDA-MB-361	Breast adenocarcinoma	Homo sapiens	CVCL_0620
	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
	HEK293T	Normal	Homo sapiens	CVCL_0063
	BT-549	Invasive breast carcinoma	Homo sapiens	CVCL_1092
	BT-474	Invasive breast carcinoma	Homo sapiens	CVCL_0179
	AU565	Breast adenocarcinoma	Homo sapiens	CVCL_1074
In-vivo Model	Luciferase-labeled rSKBR3 and MDA-MB-361 cells (1 × 10⁷ cells) mixed with 1:1 Matrigel (Corning, 356237) were subcutaneously injected into the fat pads of mice. After a tumor was palpable, the mice were randomized into four groups (five mice per group), and they were treated with vehicle, trastuzumab (20 mg/kg, intraperitoneal administration), roblitinib (30 mg/kg, oral administration), or a combination of both drugs.
Response Summary	m6A-hypomethylation regulated FGFR4 phosphorylates Glycogen synthase kinase-3 beta (GSK3Beta/GSK3B) and activates beta-catenin/TCF4-SLC7A11/FPN1 signaling to drive anti-HER2 resistance. Knockdown of METTL14 significantly increased the expression level of FGFR4 in HER2-positive breast cancer cells. FGFR4 reduced the sensitivity of HER2-positive breast cancer to trastuzumab plus pertuzumab or tucatinib. These results pinpoint a mechanism of anti-HER2 resistance and provide a strategy for overcoming resistance via FGFR4 inhibition in recalcitrant HER2-positive breast cancer.

Hepatocyte nuclear factor 3-gamma (HNF3gamma/FOXA3)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL14*
Cell Line	mouse embryonic stem cells	Mus musculus
Treatment: METTL14-/- ESCs Control: Wild type ESCs		GSE145309
Regulation		logFC: -4.46E+00 p-value: 6.08E-19
More Results	Click to View More RNA-seq Results

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

Meltrin-beta (ADAM19)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL14*
Cell Line	MDA-MB-231	Homo sapiens
Treatment: siMETTL14 MDA-MB-231 cells Control: MDA-MB-231 cells		GSE81164
Regulation		logFC: -1.69E+00 p-value: 2.38E-31
More Results	Click to View More RNA-seq Results

Ethyl ester form of 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				[31]
Responsed Disease	Glioblastoma		ICD-11: 2A00.00	Disease Info
Target Regulation	Down regulation
Cell Process	Cells growth
	Cells self-renewal
	Tumorigenesis
	MicroRNAs in cancer (hsa05206)
In-vitro Model	GSC	Glioma	Epinephelus akaara	CVCL_M752
In-vivo Model	2 × 10⁵ dissociated cells in 2 uL PBS were injected into the following site (anteroposterior [AP] +0.6 mm, mediolateral [ML] +1.6 mm, and dorsoventricular [DV] 2.6 mm) with a rate of 1 uL/min.
Response Summary	Knockdown of METTL3 or METTL14 induced changes in mRNA m6A enrichment and altered mRNA expression of genes (e.g., Meltrin-beta (ADAM19)) with critical biological functions in GSCs. Treatment with MA2, a chemical inhibitor of FTO, dramatically suppressed GSC-induced tumorigenesis and prolonged lifespan in GSC-grafted animals.

NAD-dependent protein deacetylase sirtuin-1 (SIRT1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL14*
Cell Line	HepG2 cell line	Homo sapiens
Treatment: shMETTL14 HepG2 cells Control: shCtrl HepG2 cells		GSE121949
Regulation		logFC: -7.26E-01 p-value: 1.60E-02
More Results	Click to View More RNA-seq Results

Doxil [Approved]

In total 1 item(s) under this drug			Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene			[37]
Responsed Disease	Chronic kidney disease	ICD-11: GB61.Z	Disease Info
Target Regulation	Down regulation
Cell Process	Cell apoptosis
In-vitro Model	Conditionally immortalized human podocytes (Podocytes)
In-vivo Model	To establish mice model with ADR nephropathy, adult male C57BL/6J mice (8-12 weeks of age) were purchased from Animal Center of Fudan University and injected with 19.5 mg/kg ADR (D1515, Sigma-Aldrich, St-Louis, MO, USA) intravenously via tail vein.
Response Summary	The elevated m6A RNA levels and the most upregulated METTL14 expression in kidneys of mice with adriamycin and diabetic nephropathy. METTL14-dependent RNA m6A modification contributes to podocyte injury through posttranscriptional regulation of NAD-dependent protein deacetylase sirtuin-1 (SIRT1) mRNA, which provide a potential approach for the diagnosis and treatment of podocytopathies.

PI3-kinase subunit beta (PIK3CB)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL14*
Cell Line	MDA-MB-231	Homo sapiens
Treatment: siMETTL14 MDA-MB-231 cells Control: MDA-MB-231 cells		GSE81164
Regulation		logFC: 5.88E-01 p-value: 1.08E-05
More Results	Click to View More RNA-seq Results

AZD6482 [Terminated]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[44]
Responsed Disease	Pancreatic cancer		ICD-11: 2C10	Disease Info
Target Regulation	Up regulation
Pathway Response	PI3K-Akt signaling pathway			hsa04151
	Glycolysis / Gluconeogenesis			hsa00010
Cell Process	Glucose metabolism
In-vitro Model	BxPC-3	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0186
	PANC-1	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0480
In-vivo Model	Established cohorts of mice bearing tumour xenografts driven by PTEN-deficient BxPC-3 and PANC-1 cells with PIK3CB overexpression. When tumours grew to ~300 mm³, mice were grouped and administered with vehicle (DMSO) or KIN-193 via intraperitoneal injection (20 mg/kg) once daily.
Response Summary	N6-methyladenosine mRNA methylation of PIK3CB regulates AKT signalling to promote PTEN-deficient pancreatic cancer progression. Rs142933486 is significantly associated with the overall survival of PDAC by reducing the PIK3CB m6A level, which facilitated its mRNA and protein expression levels mediated by the m6A 'writer' complex (METTL13/METTL14/WTAP) and the m6A 'reader' YTHDF2. KIN-193, a PI3-kinase subunit beta (PIK3CB)-selective inhibitor, is shown to serve as an effective anticancer agent for blocking PTEN-deficient PDAC.

Solute carrier family 40 member 1 (FPN1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL14*
Cell Line	HepG2 cell line	Homo sapiens
Treatment: shMETTL14 HepG2 cells Control: shCtrl HepG2 cells		GSE121949
Regulation		logFC: 1.09E+00 p-value: 8.51E-14
More Results	Click to View More RNA-seq Results

Pertuzumab [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[8]
Responsed Disease	Breast cancer		ICD-11: 2C60	Disease Info
Target Regulation	Down regulation
Pathway Response	Wnt signaling pathway			hsa04310
Cell Process	Glutathione synthesis
In-vitro Model	ZR-75-1	Invasive breast carcinoma	Homo sapiens	CVCL_0588
	T-47D	Invasive breast carcinoma	Homo sapiens	CVCL_0553
	SUM-159 (A mesenchymal triple-negative breast cancer cell line)
	SK-BR-3	Breast adenocarcinoma	Homo sapiens	CVCL_0033
	MDA-MB-468	Breast adenocarcinoma	Homo sapiens	CVCL_0419
	MDA-MB-453	Breast adenocarcinoma	Homo sapiens	CVCL_0418
	MDA-MB-361	Breast adenocarcinoma	Homo sapiens	CVCL_0620
	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
	HEK293T	Normal	Homo sapiens	CVCL_0063
	BT-549	Invasive breast carcinoma	Homo sapiens	CVCL_1092
	BT-474	Invasive breast carcinoma	Homo sapiens	CVCL_0179
	AU565	Breast adenocarcinoma	Homo sapiens	CVCL_1074
In-vivo Model	Luciferase-labeled rSKBR3 and MDA-MB-361 cells (1 × 10⁷ cells) mixed with 1:1 Matrigel (Corning, 356237) were subcutaneously injected into the fat pads of mice. After a tumor was palpable, the mice were randomized into four groups (five mice per group), and they were treated with vehicle, trastuzumab (20 mg/kg, intraperitoneal administration), roblitinib (30 mg/kg, oral administration), or a combination of both drugs.
Response Summary	m6A-hypomethylation regulated FGFR4 phosphorylates GSK-3beta and activates beta-catenin/TCF4-SLC7A11/Solute carrier family 40 member 1 (FPN1) signaling to drive anti-HER2 resistance. Knockdown of METTL14 significantly increased the expression level of FGFR4 in HER2-positive breast cancer cells. FGFR4 reduced the sensitivity of HER2-positive breast cancer to trastuzumab plus pertuzumab or tucatinib. These results pinpoint a mechanism of anti-HER2 resistance and provide a strategy for overcoming resistance via FGFR4 inhibition in recalcitrant HER2-positive breast cancer.

Trastuzumab [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[8]
Responsed Disease	Breast cancer		ICD-11: 2C60	Disease Info
Target Regulation	Down regulation
Pathway Response	Wnt signaling pathway			hsa04310
Cell Process	Glutathione synthesis
In-vitro Model	ZR-75-1	Invasive breast carcinoma	Homo sapiens	CVCL_0588
	T-47D	Invasive breast carcinoma	Homo sapiens	CVCL_0553
	SUM-159 (A mesenchymal triple-negative breast cancer cell line)
	SK-BR-3	Breast adenocarcinoma	Homo sapiens	CVCL_0033
	MDA-MB-468	Breast adenocarcinoma	Homo sapiens	CVCL_0419
	MDA-MB-453	Breast adenocarcinoma	Homo sapiens	CVCL_0418
	MDA-MB-361	Breast adenocarcinoma	Homo sapiens	CVCL_0620
	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
	HEK293T	Normal	Homo sapiens	CVCL_0063
	BT-549	Invasive breast carcinoma	Homo sapiens	CVCL_1092
	BT-474	Invasive breast carcinoma	Homo sapiens	CVCL_0179
	AU565	Breast adenocarcinoma	Homo sapiens	CVCL_1074
In-vivo Model	Luciferase-labeled rSKBR3 and MDA-MB-361 cells (1 × 10⁷ cells) mixed with 1:1 Matrigel (Corning, 356237) were subcutaneously injected into the fat pads of mice. After a tumor was palpable, the mice were randomized into four groups (five mice per group), and they were treated with vehicle, trastuzumab (20 mg/kg, intraperitoneal administration), roblitinib (30 mg/kg, oral administration), or a combination of both drugs.
Response Summary	m6A-hypomethylation regulated FGFR4 phosphorylates GSK-3beta and activates beta-catenin/TCF4-SLC7A11/Solute carrier family 40 member 1 (FPN1) signaling to drive anti-HER2 resistance. Knockdown of METTL14 significantly increased the expression level of FGFR4 in HER2-positive breast cancer cells. FGFR4 reduced the sensitivity of HER2-positive breast cancer to trastuzumab plus pertuzumab or tucatinib. These results pinpoint a mechanism of anti-HER2 resistance and provide a strategy for overcoming resistance via FGFR4 inhibition in recalcitrant HER2-positive breast cancer.

Tucatinib [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[8]
Responsed Disease	Breast cancer		ICD-11: 2C60	Disease Info
Target Regulation	Down regulation
Pathway Response	Wnt signaling pathway			hsa04310
Cell Process	Glutathione synthesis
In-vitro Model	ZR-75-1	Invasive breast carcinoma	Homo sapiens	CVCL_0588
	T-47D	Invasive breast carcinoma	Homo sapiens	CVCL_0553
	SUM-159 (A mesenchymal triple-negative breast cancer cell line)
	SK-BR-3	Breast adenocarcinoma	Homo sapiens	CVCL_0033
	MDA-MB-468	Breast adenocarcinoma	Homo sapiens	CVCL_0419
	MDA-MB-453	Breast adenocarcinoma	Homo sapiens	CVCL_0418
	MDA-MB-361	Breast adenocarcinoma	Homo sapiens	CVCL_0620
	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
	HEK293T	Normal	Homo sapiens	CVCL_0063
	BT-549	Invasive breast carcinoma	Homo sapiens	CVCL_1092
	BT-474	Invasive breast carcinoma	Homo sapiens	CVCL_0179
	AU565	Breast adenocarcinoma	Homo sapiens	CVCL_1074
In-vivo Model	Luciferase-labeled rSKBR3 and MDA-MB-361 cells (1 × 10⁷ cells) mixed with 1:1 Matrigel (Corning, 356237) were subcutaneously injected into the fat pads of mice. After a tumor was palpable, the mice were randomized into four groups (five mice per group), and they were treated with vehicle, trastuzumab (20 mg/kg, intraperitoneal administration), roblitinib (30 mg/kg, oral administration), or a combination of both drugs.
Response Summary	m6A-hypomethylation regulated FGFR4 phosphorylates GSK-3beta and activates beta-catenin/TCF4-SLC7A11/Solute carrier family 40 member 1 (FPN1) signaling to drive anti-HER2 resistance. Knockdown of METTL14 significantly increased the expression level of FGFR4 in HER2-positive breast cancer cells. FGFR4 reduced the sensitivity of HER2-positive breast cancer to trastuzumab plus pertuzumab or tucatinib. These results pinpoint a mechanism of anti-HER2 resistance and provide a strategy for overcoming resistance via FGFR4 inhibition in recalcitrant HER2-positive breast cancer.

TNF receptor-associated factor 1 (TRAF1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL14*
Cell Line	MDA-MB-231	Homo sapiens
Treatment: siMETTL14 MDA-MB-231 cells Control: MDA-MB-231 cells		GSE81164
Regulation		logFC: -8.04E-01 p-value: 5.72E-05
More Results	Click to View More RNA-seq Results

Sunitinib [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[50]
Responsed Disease	Renal cell carcinoma		ICD-11: 2C90	Disease Info
Target Regulation	Up regulation
Cell Process	RNA stability
Cell Process	Cell apoptosis
In-vitro Model	OS-RC-2	Clear cell renal cell carcinoma	Homo sapiens	CVCL_1626
	HUVEC-C	Normal	Homo sapiens	CVCL_2959
	786-O	Renal cell carcinoma	Homo sapiens	CVCL_1051
In-vivo Model	For the xenograft tumor model, approximately 1 × 10⁶ ccRCC cells suspended in 100 uL PBS were subcutaneously inoculated in the right flank of 5-week-old BALB/c nude mice. For the ccRCC orthotopic implantation model, approximately 1 × 10⁶ ccRCC cells suspended in 30 uL Matrigel were injected under the renal capsule of 5-week-old BALB/c nude mice. After 6 weeks, the anesthetized mice were intraperitoneally injected with D-luciferin (Yeason) and imaged using an in vivo imaging system to detect tumor growth and metastasis. For the lung metastasis model, approximately 5 × 10⁵ ccRCC cells suspended in PBS were injected into the tail vein of 5-week-old mice. After 6-8 weeks, mice were anesthetized and lung metastasis was imaged as above.
Response Summary	In renal cell carcinoma, overexpression of TNF receptor-associated factor 1 (TRAF1) promotes sunitinib resistance by modulating apoptotic and angiogenic pathways in a METTL14-dependent manner.

Transcription factor E2F8 (E2F8)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL14*
Cell Line	MDA-MB-231	Homo sapiens
Treatment: siMETTL14 MDA-MB-231 cells Control: MDA-MB-231 cells		GSE81164
Regulation		logFC: -6.53E-01 p-value: 4.62E-05
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				[51]
Responsed Disease	Breast cancer		ICD-11: 2C60	Disease Info
Target Regulation	Up regulation
Pathway Response	Nucleotide excision repair			hsa03420
Cell Process	RNA stability
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
In-vivo Model	1×10⁶ MDA-MB-231 cells were resuspended in 100 uL PBS with 50% Matrigel (Corning Costar, USA), and injected into the mammary fat pad of the mice.
Response Summary	In breast cancer, accordingly YTHDF1 knockdown sensitizes breast cancer cells to Adriamycin and Cisplatin as well as Olaparib, a PARP inhibitor. Transcription factor E2F8 (E2F8) is a target molecule by YTHDF1 which modulates E2F8 mRNA stability and DNA damage repair in a METTL14-dependent manner.

Doxil [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[51]
Responsed Disease	Breast cancer		ICD-11: 2C60	Disease Info
Target Regulation	Up regulation
Pathway Response	Nucleotide excision repair			hsa03420
Cell Process	RNA stability
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
In-vivo Model	1×10⁶ MDA-MB-231 cells were resuspended in 100 uL PBS with 50% Matrigel (Corning Costar, USA), and injected into the mammary fat pad of the mice.
Response Summary	In breast cancer, accordingly YTHDF1 knockdown sensitizes breast cancer cells to Adriamycin and Cisplatin as well as Olaparib, a PARP inhibitor. Transcription factor E2F8 (E2F8) is a target molecule by YTHDF1 which modulates E2F8 mRNA stability and DNA damage repair in a METTL14-dependent manner.

Olaparib [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[51]
Responsed Disease	Breast cancer		ICD-11: 2C60	Disease Info
Target Regulation	Up regulation
Pathway Response	Nucleotide excision repair			hsa03420
Cell Process	RNA stability
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
In-vivo Model	1×10⁶ MDA-MB-231 cells were resuspended in 100 uL PBS with 50% Matrigel (Corning Costar, USA), and injected into the mammary fat pad of the mice.
Response Summary	In breast cancer, accordingly YTHDF1 knockdown sensitizes breast cancer cells to Adriamycin and Cisplatin as well as Olaparib, a PARP inhibitor. Transcription factor E2F8 (E2F8) is a target molecule by YTHDF1 which modulates E2F8 mRNA stability and DNA damage repair in a METTL14-dependent manner.

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

Target Gene

Regorafenib [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	Liver hepatocellular carcinoma		ICD-11: 2C12.02	Disease Info
In-vitro Model	Huh-7	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0336
	SK-HEP-1	Liver and intrahepatic bile duct epithelial neoplasm	Homo sapiens	CVCL_0525
	HCCLM3	Adult hepatocellular carcinoma	Homo sapiens	CVCL_6832
	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
In-vivo Model	After one week of acclimatization, the nude mice were randomly divided into 5 groups (n = 3): Control, vehicle + oe-NC, vehicle + oe-CHOP, Regorafenib + oe-NC, and Regorafenib + oe-CHOP. The Control group was injected with untreated SK-Hep-1 cells. The vehicle + oe-NC group and Regorafenib + oe-NC group were injected with SK-Hep-1 cells transfected with oe-NC. vehicle + oe-CHOP group and Regorafenib + oe-CHOP group were injected with SK-Hep-1 cells transfected with oe-CHOP.

Pancreas/duodenum homeobox protein 1 (Pdx1)

Target Gene

Bisphenol F [Investigative]

In total 1 item(s) under this drug		Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene		[83]
Target Regulation	Up regulation

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

Target Gene

Arsenite [Phase 2]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[85]
Responsed Disease	Diabetic		ICD-11: 5A14	Disease Info
In-vitro Model	L-02	Endocervical adenocarcinoma	Homo sapiens	CVCL_6926

Sequestosome-1 (SQSTM1)

Target Gene

Paclitaxel [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	HEK293T	Normal	Homo sapiens	CVCL_0063
In-vivo Model	The experimental mice were housed in an SPF-grade animal laboratory at a temperature of approximately 25 °C, a humidity range of 50%, and an average daylight duration of 12 h. BALB/C female mice at 5-7 weeks of age were taken and prepared for tumor-bearing. After the mice were sacrificed, their tissues were collected, weighed and immediately snap-frozen in liquid nitrogen.

STM2457 [Investigative]

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	HEK293T	Normal	Homo sapiens	CVCL_0063
In-vivo Model	The experimental mice were housed in an SPF-grade animal laboratory at a temperature of approximately 25 °C, a humidity range of 50%, and an average daylight duration of 12 h. BALB/C female mice at 5-7 weeks of age were taken and prepared for tumor-bearing. After the mice were sacrificed, their tissues were collected, weighed and immediately snap-frozen in liquid nitrogen.

hsa_circ_0008399 (Circ_RBM3)

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				[115]
Responsed Disease	Bladder cancer		ICD-11: 2C94	Disease Info
Target Regulation	Up regulation
Pathway Response	Protein export			hsa03060
Cell Process	Eukaryotic translation
Cell Process	Cell apoptosis
In-vitro Model	5637	Bladder carcinoma	Homo sapiens	CVCL_0126
	RT-4	Bladder carcinoma	Homo sapiens	CVCL_0036
	UM-UC-3	Bladder carcinoma	Homo sapiens	CVCL_1783
In-vivo Model	Chose 4-week-old female BALB/c nude mice for tumor xenograft experiments, which randomly were divided into four groups (n = 5 per group). Bladder cancer cells (3 × 10⁶) were subcutaneously injected into the right axilla of the nude mice.
Response Summary	Circ0008399 bound WTAP to promote formation of the WTAP/METTL3/METTL14 m6A methyltransferase complex, reduce cisplatin sensitivity in bladder cancer, implicating the potential therapeutic value of targeting this axis.

C-C motif chemokine 5 (CCL5)

Target Gene

Fentanyl [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[124]
Responsed Disease	Gestational diabetes mellitus		ICD-11: JA63	Disease Info
Target Regulation	Up regulation
In-vitro Model	HPDE6c7	Normal	Homo sapiens	CVCL_0P38
	Capan-1	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0237
	SW1990	Pancreatic adenocarcinoma	Homo sapiens	CVCL_1723
	CFPAC-1	Cystic fibrosis	Homo sapiens	CVCL_1119

Calcium-binding and coiled-coil domain-containing protein 1 (CALCOCO1)

Target Gene

Paclitaxel [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	HEK293T	Normal	Homo sapiens	CVCL_0063
In-vivo Model	The experimental mice were housed in an SPF-grade animal laboratory at a temperature of approximately 25 °C, a humidity range of 50%, and an average daylight duration of 12 h. BALB/C female mice at 5-7 weeks of age were taken and prepared for tumor-bearing. After the mice were sacrificed, their tissues were collected, weighed and immediately snap-frozen in liquid nitrogen.

STM2457 [Investigative]

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	HEK293T	Normal	Homo sapiens	CVCL_0063
In-vivo Model	The experimental mice were housed in an SPF-grade animal laboratory at a temperature of approximately 25 °C, a humidity range of 50%, and an average daylight duration of 12 h. BALB/C female mice at 5-7 weeks of age were taken and prepared for tumor-bearing. After the mice were sacrificed, their tissues were collected, weighed and immediately snap-frozen in liquid nitrogen.

Ferroptosis suppressor protein 1 (AIFM2)

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				[133]
Responsed Disease	Esophageal cancer		ICD-11: 2B70	Disease Info
In-vitro Model	TE-1	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1759
In-vitro Model	KYSE-150	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1348
In-vivo Model	The KYSE-150 cells were subcutaneously inoculated on the right side at a dosage of 10⁶ cells per mouse. After the tumor grew to approximately 50 mm3, mice were randomly divided into four groups (n = 6): Control, CisR-exo, Cis, and Cis + CisR-exo. Then, normal saline or cisplatin (20 mg/kg; twice a week) was intratumorally injected alone or combined with CisR-exos (10 μg; once every two days).

Hamartin (TSC1)

Target Gene

Coptisine [Investigative]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[135]
Responsed Disease	Ulcerative colitis		ICD-11: DD71	Disease Info
Target Regulation	Up regulation
In-vitro Model	RAW 264.7	Mouse leukemia	Mus musculus	CVCL_0493
In-vivo Model	Sixty mice were disposed in 6 groups randomly by using spss25.0 software after an adaption period of one week (n = 10): control, DSS model, 5-ASA (200 mg/kg) +DSS, coptisine 25 mg/kg + DSS (COP-l), coptisine 50 mg/kg + DSS (COP-M) and coptisine 100 mg/kg + DSS (COP-H). The dosages of 5-ASA and COP were implemented in accordance with the previous report.

HOX transcript antisense RNA (HOTAIR)

Target Gene

MM-102 [Investigative]

In total 1 item(s) under this drug			Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene			[137]
Responsed Disease	Disorders due to use of opioids	ICD-11: 6C43.1	Disease Info
Target Regulation	Up regulation

Mitogen-activated protein kinase 13 (MAPK13)

Target Gene

Rapamycin [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[148]
Target Regulation	Down regulation
In-vitro Model	621-101	Lung lymphangioleiomyomatosis	Homo sapiens	CVCL_S879
	HEK293-EBNA	N.A.	Homo sapiens	CVCL_6974
	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
	BT-549	Invasive breast carcinoma	Homo sapiens	CVCL_1092
	UMB1949	Kidney angiomyolipoma	Homo sapiens	CVCL_C471

Neurotrophic factor BDNF precursor form (BDNF)

Target Gene

Xuefu Zhuyu decoction [Investigative]

In total 1 item(s) under this drug			Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene			[149]
Responsed Disease	Traumatic brain injury induced by controlled cortical impact injury	ICD-11: NA07	Disease Info
Target Regulation	Up regulation
In-vivo Model	Adult male Sprague-Dawley rats (body weight 220 g-250 g) were acquired from Hunan Silaike Jingda Laboratory Animal Co., Ltd. (Changsha, China, license No. SCXK (XIANG) 2016-0002). They were housed under specific pathogen-free conditions in the Department of Laboratory Animals, Central South University (Changsha, China, license No. SYXK (XIANG) 2015-0017). All rats were kept in air-conditioned animal quarters under standard conditions (50 ± 10% relative humidity, 12-h light/dark cycle, 22 ± 2 °C), with ad libitum water and food.

pri-miR-17

Target Gene

Fluorouracil [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[157]
Responsed Disease	Colorectal cancer		ICD-11: 2B91	Disease Info
Target Regulation	Up regulation
In-vitro Model	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	LoVo	Colon adenocarcinoma	Homo sapiens	CVCL_0399
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
	SW620	Colon adenocarcinoma	Homo sapiens	CVCL_0547
	Caco-2	Colon adenocarcinoma	Homo sapiens	CVCL_0025
	HT29	Colon cancer	Mus musculus	CVCL_A8EZ
	RKO	Colon carcinoma	Homo sapiens	CVCL_0504
	FHC	Normal	Homo sapiens	CVCL_3688
	NCM460	Normal	Homo sapiens	CVCL_0460

Protein disulfide-isomerase (P4HB)

Target Gene

ICARIIN [Investigative]

In total 1 item(s) under this drug			Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene			[159]
Responsed Disease	Osteoporosis	ICD-11: FB83.1	Disease Info
In-vivo Model	After anesthesia with ketamine-xylazine(intraperitoneal injection, 60 and 5 mg/kg, respectively), the rats were operated to remove the bilateral ovaries. For the rats in the Sham group, only the fat around the ovaries was surgically removed. Four weeks after the operation, the animals were orally treated with ICA (250 mg/kg) daily for 10 weeks .

Pseudorabies Virus (PRV)

Target Gene

3-deazidenosine [Investigative]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[160]
Responsed Disease	Rabies		ICD-11: 1C82	Disease Info
Target Regulation	Up regulation
In-vitro Model	PK-15	N.A.	Sus scrofa	CVCL_2160

SREBF2 antisense RNA 1 (SREBF2-AS1)

Target Gene

Sorafenib [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[166]
Responsed Disease	Liver hepatocellular carcinoma		ICD-11: 2C12.02	Disease Info
Target Regulation	Up regulation
In-vitro Model	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
	SNU-398	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0077
	THLE-2	Normal	Homo sapiens	CVCL_3803
	Huh-7	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0336

TNF and HNRNPL related immunoregulatory long non-coding RNA (THRIL)

Target Gene

LPS [Investigative]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[168]
Responsed Disease	Injury of other or unspecified intrathoracic organs		ICD-11: NB32.3	Disease Info
Target Regulation	Up regulation
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023

Transmembrane protein 127 (TMEM127)

Target Gene

Rapamycin [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[171]
Responsed Disease	Breast cancer		ICD-11: 2C60	Disease Info
Target Regulation	Up regulation
In-vitro Model	MDA-MB-231	Breast adenocarcinoma	Homo sapiens	CVCL_0062
	T-47D	Invasive breast carcinoma	Homo sapiens	CVCL_0553
	HEK293T	Normal	Homo sapiens	CVCL_0063
In-vivo Model	Approximately 1 × 10⁶ viable MDA-MB-231 breast cancer cells were resuspended in 1:1 ratio in 50 μl medium and 50 μl matrigel (Corning, 354234) and injected orthotopically into the fourth mammary fat pad of each mouse. After injection, tumor size was measured twice a week using an electronic caliper. Tumor volumes were calculated with the formula: volume = (L × W2)/2, where L is the tumor length and W is the tumor width measured in millimeters.

Unspecific Target Gene

Arsenite [Phase 2]

In total 1 item(s) under this drug		Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene		[177]
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.

Gemcitabine [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[183]
Responsed Disease	Pancreatic cancer		ICD-11: 2C10	Disease Info
In-vitro Model	PANC-1	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0480
	BxPC-3	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0186
	MIA PaCa-2	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0428
	Hs 766T	Pancreatic adenocarcinoma	Homo sapiens	CVCL_0334
	AsPC-1	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0152
	Capan-2	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0026
In-vivo Model	NOD/SCID mice (6-week-old) were injected (subcutaneously in both flanks) with 5.0 x 10⁶ PANC-1 GemR cells (infected with scr or METTL14 shRNA) per mouse suspended in 50 ul PBS and mixed with equal volume of growth factor reduced matrigel. One week after injection, we started measuring tumor size at the indicated times. Tumor size was calculated by 0.5 × (long diameter) × (short diameter)2. The mice were treated with vehicle or 100 mg/kg gemcitabine intraperitoneally twice a week.
Response Summary	Suppression of METTL14 obviously increased the sensitivity of gemcitabine in resistant cells. This study suggested that METTL14 is a potential target for chemotherapy resistance in pancreatic cancer.

Tamoxifen [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[192]
Responsed Disease	Glucose Intolerance		ICD-11: 5C61.Y	Disease Info
In-vitro Model	MIN6	Mouse insulinoma	Mus musculus	CVCL_0431
In-vivo Model	The mice were fed a normal chow diet (Harlan Teklad) and maintained in a standard 12-hour light/12-hour dark cycle. At the age of 10 weeks, both male and female mice were intraperitoneally injected with 250 L (20 mg/mL) tamoxifen every other day for three times to delete Mettl14 in Beta-cells. Intraperitoneal glucose tolerance tests were performed on mice at the age of 15 weeks after a 5-hour fast (2 g/kg dextrose). Insulin levels were measured at 0, 15, and 30 minutes after glucose challenge by using the Ultra Sensitive Mouse Insulin ELISA Kit .Insulin tolerance tests were performed after a 5-hour fast by administering human recombinant insulin (0.75 U/kg).
Response Summary	METTL14 deficiency in beta-cells induces glucose intolerance and a decrease in insulin secretion.To define the role of m6A in regulating the beta-cell function, the study generated beta-cell METTL14-specific knockout (beta-KO) mice by tamoxifen administration. beta-cell mass in beta-KO mice was related to beta-cell proliferation and also observed elevated mRNA and protein levels of Ire1-alpha and sXBP-1 in beta-KO islets.

Betaine [Approved]

In total 1 item(s) under this drug			Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene			[193]
Responsed Disease	Epilepsy due to structural or metabolic conditions or diseases	ICD-11: 8A60.5	Disease Info
Target Regulation	Down regulation
In-vivo Model	Mice were treated with a single i.p. injection of pentylenetetrazol (PTZ, Sigma-Aldrich, P6500) at a dose of 50 mg/kg to establish the animal model of acute seizures [16]. Betaine (Sigma-Aldrich, B2629) was dissolved in normal saline, and administrated at a dose of 200 mg/kg or 600 mg/kg, i.p., to mice for 15 days before PTZ injection in reference to a previous study.

Sunitinib [Approved]

In total 1 item(s) under this drug			Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene			[196]
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).

Ethyl ester form of 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				[197]
Responsed Disease	Male infertility		ICD-11: GB04	Disease Info
Cell Process	Cell cycle
	Cell proliferation
In-vitro Model	GC-1 spg	Normal	Mus musculus	CVCL_8872
	HEK293T	Normal	Homo sapiens	CVCL_0063
In-vivo Model	Mouse GC-1 spg cells were treated with the ester form of meclofenamic acid (MA2) to inhibit the demethylase activity of FTO.
Response Summary	METTL3, METTL14, ALKBH5 and YTHDC2 are involved in the regulation of spermatogenesis and oogenesis. MA2 affected CDKs expression through the m6A-dependent mRNA degradation pathway, and thus repressed spermatogonial proliferation. Additionally, mutation of the predicted m6A sites in the Cdk2-3'UTR could mitigated the degradation of CDK2 mRNA after MA2 treatment.

Click to View Potential Drug Response of This Regulator

Full List of Crosstalk(s) between m6A Modification and Epigenetic Regulation Related to This Regulator

RNA modification

m6A Target: Cyclin-dependent kinase inhibitor 1 (CDKN1A)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT00002		Crosstalk Info
Epigenetic Regulator	RNA cytosine C(5)-methyltransferase NSUN2 (NSUN2)
Regulated Target	Cyclin-dependent kinase inhibitor 1 (CDKN1A)
Crosstalk relationship	m5C → m6A

m6A Target: Mutated in multiple advanced cancers 1 (PTEN)

Target Gene

In total 4 item(s) under this m6A target
Crosstalk ID: M6ACROT00413		Crosstalk Info
Epigenetic Regulator	Double-stranded RNA-specific editase 1 (ADARB1)
Regulated Target	MicroRNA 21 (MIR21)
Crosstalk relationship	A-to-I → m6A
Crosstalk ID: M6ACROT00414		Crosstalk Info
Epigenetic Regulator	Interferon-inducible protein 4 (ADAR1)
Regulated Target	MicroRNA 21 (MIR21)
Crosstalk relationship	A-to-I → m6A
Crosstalk ID: M6ACROT00448		Crosstalk Info
Epigenetic Regulator	Double-stranded RNA-specific editase 1 (ADARB1)
Regulated Target	MicroRNA 214 (MIR214)
Crosstalk relationship	A-to-I → m6A
Crosstalk ID: M6ACROT00512		Crosstalk Info
Epigenetic Regulator	Interferon-inducible protein 4 (ADAR1)
Regulated Target	hsa-mir-18a
Crosstalk relationship	A-to-I → m6A

m6A Target: X inactive specific transcript (XIST)

Target Gene

In total 2 item(s) under this m6A target
Crosstalk ID: M6ACROT00427		Crosstalk Info
Epigenetic Regulator	Double-stranded RNA-specific editase 1 (ADARB1)
Regulated Target	MicroRNA 21 (MIR21)
Crosstalk relationship	m6A → A-to-I
Crosstalk ID: M6ACROT00428		Crosstalk Info
Epigenetic Regulator	Interferon-inducible protein 4 (ADAR1)
Regulated Target	MicroRNA 21 (MIR21)
Crosstalk relationship	m6A → A-to-I

m6A Target: Nuclear paraspeckle assembly transcript 1 (NEAT1)

Target Gene

In total 4 item(s) under this m6A target
Crosstalk ID: M6ACROT00435		Crosstalk Info
Epigenetic Regulator	Methyltransferase-like protein 1 (METTL1)
Regulated Target	MicroRNA 125a (MIR125A)
Crosstalk relationship	m6A → m7G
Crosstalk ID: M6ACROT00440		Crosstalk Info
Epigenetic Regulator	Double-stranded RNA-specific editase 1 (ADARB1)
Regulated Target	MicroRNA 214 (MIR214)
Crosstalk relationship	m6A → A-to-I
Crosstalk ID: M6ACROT00474		Crosstalk Info
Epigenetic Regulator	Interferon-inducible protein 4 (ADAR1)
Regulated Target	MicroRNA 181a-1 (MIR181A1)
Crosstalk relationship	m6A → A-to-I
Crosstalk ID: M6ACROT00476		Crosstalk Info
Epigenetic Regulator	Interferon-inducible protein 4 (ADAR1)
Regulated Target	MicroRNA 155 (MIR155)
Crosstalk relationship	m6A → A-to-I

m6A Target: Epidermal growth factor receptor (EGFR)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT00444		Crosstalk Info
Epigenetic Regulator	Double-stranded RNA-specific editase 1 (ADARB1)
Regulated Target	MicroRNA 214 (MIR214)
Crosstalk relationship	A-to-I → m6A

m6A Target: High mobility group protein HMGI-C (HMGA2)

Target Gene

In total 2 item(s) under this m6A target
Crosstalk ID: M6ACROT00467		Crosstalk Info
Epigenetic Regulator	Interferon-inducible protein 4 (ADAR1)
Regulated Target	MicroRNA 149 (MIR149)
Crosstalk relationship	A-to-I → m6A
Crosstalk ID: M6ACROT00468		Crosstalk Info
Epigenetic Regulator	Methyltransferase-like protein 1 (METTL1)
Regulated Target	MicroRNA 149 (MIR149)
Crosstalk relationship	m7G → m6A

m6A Target: KCNQ1 opposite strand/antisense transcript 1 (KCNQ1OT1)

Target Gene

In total 2 item(s) under this m6A target
Crosstalk ID: M6ACROT00471		Crosstalk Info
Epigenetic Regulator	Interferon-inducible protein 4 (ADAR1)
Regulated Target	MicroRNA 149 (MIR149)
Crosstalk relationship	m6A → A-to-I
Crosstalk ID: M6ACROT00472		Crosstalk Info
Epigenetic Regulator	Methyltransferase-like protein 1 (METTL1)
Regulated Target	MicroRNA 149 (MIR149)
Crosstalk relationship	m6A → m7G

m6A Target: NACHT, LRR and PYD domains-containing protein 3 (NLRP3)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT00482		Crosstalk Info
Epigenetic Regulator	Fat mass and obesity-associated protein (FTO)
Regulated Target	hsa-mir-22
Crosstalk relationship	m6Am → m6A

m6A Target: Cyclin-dependent kinase inhibitor 1B (CDKN1B/p27)

Target Gene

In total 2 item(s) under this m6A target
Crosstalk ID: M6ACROT00497		Crosstalk Info
Epigenetic Regulator	Double-stranded RNA-specific editase 1 (ADARB1)
Regulated Target	MicroRNA 222 (MIR222)
Crosstalk relationship	A-to-I → m6A
Crosstalk ID: M6ACROT00498		Crosstalk Info
Epigenetic Regulator	Interferon-inducible protein 4 (ADAR1)
Regulated Target	MicroRNA 222 (MIR222)
Crosstalk relationship	A-to-I → m6A

m6A Target: Fascin (FSCN1)

Target Gene

In total 2 item(s) under this m6A target
Crosstalk ID: M6ACROT00542		Crosstalk Info
Epigenetic Regulator	Interferon-inducible protein 4 (ADAR1)
Regulated Target	MicroRNA 200b (MIR200B)
Crosstalk relationship	A-to-I → m6A
Crosstalk ID: M6ACROT00543		Crosstalk Info
Epigenetic Regulator	Y-box-binding protein 1 (YBX1)
Regulated Target	MicroRNA 200b (MIR200B)
Crosstalk relationship	m5C → m6A

m6A Target: Transcription factor SOX-6 (SOX6)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT00554		Crosstalk Info
Epigenetic Regulator	Double-stranded RNA-specific editase 1 (ADARB1)
Regulated Target	MicroRNA 122 (MIR122)
Crosstalk relationship	A-to-I → m6A

m6A Target: hsa-miR-34a

Target Gene

In total 13 item(s) under this m6A target
Crosstalk ID: M6ACROT00611		Crosstalk Info
Epigenetic Regulator	Interferon-inducible protein 4 (ADAR1)
Regulated Target	G1/S-specific cyclin-E1 (CCNE1)
Crosstalk relationship	m6A → A-to-I
Crosstalk ID: M6ACROT00612		Crosstalk Info
Epigenetic Regulator	Y-box-binding protein 1 (YBX1)
Regulated Target	G1/S-specific cyclin-E1 (CCNE1)
Crosstalk relationship	m6A → m5C
Crosstalk ID: M6ACROT00613		Crosstalk Info
Epigenetic Regulator	Methylcytosine dioxygenase TET1 (TET1)
Regulated Target	G1/S-specific cyclin-E1 (CCNE1)
Crosstalk relationship	m6A → m5C
Crosstalk ID: M6ACROT00614		Crosstalk Info
Epigenetic Regulator	Interferon-inducible protein 4 (ADAR1)
Regulated Target	Nuclear paraspeckle assembly transcript 1 (NEAT1)
Crosstalk relationship	A-to-I → m6A
Crosstalk ID: M6ACROT00615		Crosstalk Info
Epigenetic Regulator	Y-box-binding protein 1 (YBX1)
Regulated Target	Zinc finger protein SNAI1 (SNAI1)
Crosstalk relationship	m6A → m5C
Crosstalk ID: M6ACROT00616		Crosstalk Info
Epigenetic Regulator	Methylcytosine dioxygenase TET3 (TET3)
Regulated Target	Apoptosis regulator Bcl-2 (BCL2)
Crosstalk relationship	m6A → m5C
Crosstalk ID: M6ACROT00617		Crosstalk Info
Epigenetic Regulator	Y-box-binding protein 1 (YBX1)
Regulated Target	Apoptosis regulator Bcl-2 (BCL2)
Crosstalk relationship	m6A → m5C
Crosstalk ID: M6ACROT00618		Crosstalk Info
Epigenetic Regulator	Fat mass and obesity-associated protein (FTO)
Regulated Target	Apoptosis regulator Bcl-2 (BCL2)
Crosstalk relationship	m6A → m6Am
Crosstalk ID: M6ACROT00619		Crosstalk Info
Epigenetic Regulator	Pseudouridylate synthase 1 homolog (PUS1)
Regulated Target	Apoptosis regulator Bcl-2 (BCL2)
Crosstalk relationship	m6A → Pseudouridine
Crosstalk ID: M6ACROT00620		Crosstalk Info
Epigenetic Regulator	THO complex subunit 4 (ALYREF)
Regulated Target	N-myc proto-oncogene protein (MYCN)
Crosstalk relationship	m6A → m5C
Crosstalk ID: M6ACROT00621		Crosstalk Info
Epigenetic Regulator	Fat mass and obesity-associated protein (FTO)
Regulated Target	Cytochrome c, somatic (CYCS)
Crosstalk relationship	m6A → m6Am
Crosstalk ID: M6ACROT00622		Crosstalk Info
Epigenetic Regulator	Fat mass and obesity-associated protein (FTO)
Regulated Target	NAD-dependent protein deacetylase sirtuin-1 (SIRT1)
Crosstalk relationship	m6A → m6Am
Crosstalk ID: M6ACROT00623		Crosstalk Info
Epigenetic Regulator	Fat mass and obesity-associated protein (FTO)
Regulated Target	Autophagy protein 5 (ATG5)
Crosstalk relationship	m6A → m6Am

m6A Target: microRNA 126 (MIR126)

Target Gene

In total 4 item(s) under this m6A target
Crosstalk ID: M6ACROT00624		Crosstalk Info
Epigenetic Regulator	Interferon-inducible protein 4 (ADAR1)
Regulated Target	Nuclear paraspeckle assembly transcript 1 (NEAT1)
Crosstalk relationship	A-to-I → m6A
Crosstalk ID: M6ACROT00625		Crosstalk Info
Epigenetic Regulator	Alpha-ketoglutarate-dependent dioxygenase alkB homolog 3 (ALKBH3)
Regulated Target	Vascular endothelial growth factor A (VEGFA)
Crosstalk relationship	m6A → m1A
Crosstalk ID: M6ACROT00626		Crosstalk Info
Epigenetic Regulator	Methyltransferase-like protein 1 (METTL1)
Regulated Target	Vascular endothelial growth factor A (VEGFA)
Crosstalk relationship	m6A → m7G
Crosstalk ID: M6ACROT00627		Crosstalk Info
Epigenetic Regulator	Fat mass and obesity-associated protein (FTO)
Regulated Target	C-X-C chemokine receptor type 4 (CXCR4)
Crosstalk relationship	m6A → m6Am

m6A Target: hsa-mir-146a

Target Gene

In total 5 item(s) under this m6A target
Crosstalk ID: M6ACROT00628		Crosstalk Info
Epigenetic Regulator	Interferon-inducible protein 4 (ADAR1)
Regulated Target	Nuclear paraspeckle assembly transcript 1 (NEAT1)
Crosstalk relationship	A-to-I → m6A
Crosstalk ID: M6ACROT00629		Crosstalk Info
Epigenetic Regulator	Y-box-binding protein 1 (YBX1)
Regulated Target	Growth arrest specific 5 (GAS5)
Crosstalk relationship	m5C → m6A
Crosstalk ID: M6ACROT00630		Crosstalk Info
Epigenetic Regulator	THO complex subunit 4 (ALYREF)
Regulated Target	Breast cancer type 1 susceptibility protein (BRCA1)
Crosstalk relationship	m6A → m5C
Crosstalk ID: M6ACROT00631		Crosstalk Info
Epigenetic Regulator	Fat mass and obesity-associated protein (FTO)
Regulated Target	C-X-C chemokine receptor type 4 (CXCR4)
Crosstalk relationship	m6A → m6Am
Crosstalk ID: M6ACROT00632		Crosstalk Info
Epigenetic Regulator	Fat mass and obesity-associated protein (FTO)
Regulated Target	Metastasis associated lung adenocarcinoma transcript 1 (MALAT1)
Crosstalk relationship	m6Am → m6A

m6A Target: microRNA 375 (MIR375)

Target Gene

In total 6 item(s) under this m6A target
Crosstalk ID: M6ACROT00657		Crosstalk Info
Epigenetic Regulator	Y-box-binding protein 1 (YBX1)
Regulated Target	Hypoxia-inducible factor 1-alpha (HIF-1-Alpha/HIF1A)
Crosstalk relationship	m6A → m5C
Crosstalk ID: M6ACROT00658		Crosstalk Info
Epigenetic Regulator	H/ACA ribonucleoprotein complex subunit DKC1 (DKC1)
Regulated Target	Hypoxia-inducible factor 1-alpha (HIF-1-Alpha/HIF1A)
Crosstalk relationship	m6A → Pseudouridine
Crosstalk ID: M6ACROT00659		Crosstalk Info
Epigenetic Regulator	Y-box-binding protein 1 (YBX1)
Regulated Target	Transcriptional coactivator YAP1 (YAP1)
Crosstalk relationship	m6A → m5C
Crosstalk ID: M6ACROT00660		Crosstalk Info
Epigenetic Regulator	Fat mass and obesity-associated protein (FTO)
Regulated Target	NAD-dependent protein deacetylase sirtuin-1 (SIRT1)
Crosstalk relationship	m6A → m6Am
Crosstalk ID: M6ACROT00661		Crosstalk Info
Epigenetic Regulator	Fat mass and obesity-associated protein (FTO)
Regulated Target	Metastasis associated lung adenocarcinoma transcript 1 (MALAT1)
Crosstalk relationship	m6Am → m6A
Crosstalk ID: M6ACROT00662		Crosstalk Info
Epigenetic Regulator	Methyltransferase-like protein 1 (METTL1)
Regulated Target	High mobility group protein HMGI-C (HMGA2)
Crosstalk relationship	m6A → m7G

m6A Target: hsa-mir-19a

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT00673		Crosstalk Info
Epigenetic Regulator	RNA cytosine C(5)-methyltransferase NSUN2 (NSUN2)
Regulated Target	H19 imprinted maternally expressed transcript (H19)
Crosstalk relationship	m5C → m6A

DNA modification

m6A Target: Neurogenic locus notch homolog protein 2 (NOTCH2)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT02045		Crosstalk Info
Epigenetic Regulator	DNA (cytosine-5)-methyltransferase 1 (DNMT1)
Regulated Target	Neurogenic locus notch homolog protein 2 (NOTCH2)
Crosstalk relationship	m6A → DNA modification

m6A Target: SREBF2 antisense RNA 1 (SREBF2-AS1)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT02099		Crosstalk Info
Epigenetic Regulator	Methylcytosine dioxygenase TET1 (TET1)
Regulated Target	Sterol regulatory element binding transcription factor 2 (SREBF2)
Crosstalk relationship	m6A → DNA modification
Disease	Liver cancer	Disease Info

m6A Target: microRNA 375 (MIR375)

Target Gene

In total 3 item(s) under this m6A target
Crosstalk ID: M6ACROT02101		Crosstalk Info
Epigenetic Regulator	Cysteine methyltransferase DNMT3A (DNMT3A)
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	DNA modification → m6A
Disease	Breast cancer	Disease Info
Crosstalk ID: M6ACROT02102		Crosstalk Info
Epigenetic Regulator	DNA (cytosine-5)-methyltransferase 3B (DNMT3B)
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	DNA modification → m6A
Disease	Breast cancer	Disease Info
Crosstalk ID: M6ACROT02103		Crosstalk Info
Epigenetic Regulator	DNA (cytosine-5)-methyltransferase 1 (DNMT1)
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	DNA modification → m6A
Disease	Breast cancer	Disease Info

m6A Target: Phosphoenolpyruvate carboxykinase [GTP], mitochondrial (PCK2)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT02114		Crosstalk Info
Epigenetic Regulator	Methylcytosine dioxygenase TET2 (TET2)
Regulated Target	Phosphoenolpyruvate carboxykinase [GTP], mitochondrial (PCK2)
Crosstalk relationship	DNA modification → m6A
Disease	Hepatic inflammation	Disease Info

m6A Target: hsa-miR-146a-5p

Target Gene

In total 3 item(s) under this m6A target
Crosstalk ID: M6ACROT02203		Crosstalk Info
Epigenetic Regulator	DNA (cytosine-5)-methyltransferase 3B (DNMT3B)
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	DNA modification → m6A
Disease	Breast cancer	Disease Info
Crosstalk ID: M6ACROT02227		Crosstalk Info
Epigenetic Regulator	Cysteine methyltransferase DNMT3A (DNMT3A)
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	DNA modification → m6A
Disease	Breast cancer	Disease Info
Crosstalk ID: M6ACROT02251		Crosstalk Info
Epigenetic Regulator	DNA (cytosine-5)-methyltransferase 1 (DNMT1)
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	DNA modification → m6A
Disease	Breast cancer	Disease Info

m6A Target: C-X-C chemokine receptor type 4 (CXCR4)

Target Gene

In total 3 item(s) under this m6A target
Crosstalk ID: M6ACROT02204		Crosstalk Info
Epigenetic Regulator	DNA (cytosine-5)-methyltransferase 3B (DNMT3B)
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	DNA modification → m6A
Disease	Breast cancer	Disease Info
Crosstalk ID: M6ACROT02228		Crosstalk Info
Epigenetic Regulator	Cysteine methyltransferase DNMT3A (DNMT3A)
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	DNA modification → m6A
Disease	Breast cancer	Disease Info
Crosstalk ID: M6ACROT02252		Crosstalk Info
Epigenetic Regulator	DNA (cytosine-5)-methyltransferase 1 (DNMT1)
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	DNA modification → m6A
Disease	Breast cancer	Disease Info

m6A Target: Cytochrome P450 1B1 (CYP1B1)

Target Gene

In total 3 item(s) under this m6A target
Crosstalk ID: M6ACROT02205		Crosstalk Info
Epigenetic Regulator	DNA (cytosine-5)-methyltransferase 3B (DNMT3B)
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	DNA modification → m6A
Disease	Breast cancer	Disease Info
Crosstalk ID: M6ACROT02229		Crosstalk Info
Epigenetic Regulator	Cysteine methyltransferase DNMT3A (DNMT3A)
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	DNA modification → m6A
Disease	Breast cancer	Disease Info
Crosstalk ID: M6ACROT02253		Crosstalk Info
Epigenetic Regulator	DNA (cytosine-5)-methyltransferase 1 (DNMT1)
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	DNA modification → m6A
Disease	Breast cancer	Disease Info

m6A Target: Catenin beta-1 (CTNNB1/Beta-catenin)

Target Gene

In total 9 item(s) under this m6A target
Crosstalk ID: M6ACROT02206		Crosstalk Info
Epigenetic Regulator	DNA (cytosine-5)-methyltransferase 3B (DNMT3B)
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	DNA modification → m6A
Disease	Breast cancer	Disease Info
Drug	Trastuzumab	Drug Info
Crosstalk ID: M6ACROT02211		Crosstalk Info
Epigenetic Regulator	DNA (cytosine-5)-methyltransferase 3B (DNMT3B)
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	DNA modification → m6A
Disease	Breast cancer	Disease Info
Drug	Pertuzumab	Drug Info
Crosstalk ID: M6ACROT02219		Crosstalk Info
Epigenetic Regulator	DNA (cytosine-5)-methyltransferase 3B (DNMT3B)
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	DNA modification → m6A
Disease	Breast cancer	Disease Info
Drug	Tucatinib	Drug Info
Crosstalk ID: M6ACROT02230		Crosstalk Info
Epigenetic Regulator	Cysteine methyltransferase DNMT3A (DNMT3A)
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	DNA modification → m6A
Disease	Breast cancer	Disease Info
Drug	Trastuzumab	Drug Info
Crosstalk ID: M6ACROT02235		Crosstalk Info
Epigenetic Regulator	Cysteine methyltransferase DNMT3A (DNMT3A)
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	DNA modification → m6A
Disease	Breast cancer	Disease Info
Drug	Pertuzumab	Drug Info
Crosstalk ID: M6ACROT02243		Crosstalk Info
Epigenetic Regulator	Cysteine methyltransferase DNMT3A (DNMT3A)
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	DNA modification → m6A
Disease	Breast cancer	Disease Info
Drug	Tucatinib	Drug Info
Crosstalk ID: M6ACROT02254		Crosstalk Info
Epigenetic Regulator	DNA (cytosine-5)-methyltransferase 1 (DNMT1)
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	DNA modification → m6A
Disease	Breast cancer	Disease Info
Drug	Trastuzumab	Drug Info
Crosstalk ID: M6ACROT02259		Crosstalk Info
Epigenetic Regulator	DNA (cytosine-5)-methyltransferase 1 (DNMT1)
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	DNA modification → m6A
Disease	Breast cancer	Disease Info
Drug	Pertuzumab	Drug Info
Crosstalk ID: M6ACROT02267		Crosstalk Info
Epigenetic Regulator	DNA (cytosine-5)-methyltransferase 1 (DNMT1)
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	DNA modification → m6A
Disease	Breast cancer	Disease Info
Drug	Tucatinib	Drug Info

m6A Target: Cystine/glutamate transporter (SLC7A11)

Target Gene

In total 9 item(s) under this m6A target
Crosstalk ID: M6ACROT02207		Crosstalk Info
Epigenetic Regulator	DNA (cytosine-5)-methyltransferase 3B (DNMT3B)
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	DNA modification → m6A
Disease	Breast cancer	Disease Info
Drug	Trastuzumab	Drug Info
Crosstalk ID: M6ACROT02212		Crosstalk Info
Epigenetic Regulator	DNA (cytosine-5)-methyltransferase 3B (DNMT3B)
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	DNA modification → m6A
Disease	Breast cancer	Disease Info
Drug	Pertuzumab	Drug Info
Crosstalk ID: M6ACROT02220		Crosstalk Info
Epigenetic Regulator	DNA (cytosine-5)-methyltransferase 3B (DNMT3B)
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	DNA modification → m6A
Disease	Breast cancer	Disease Info
Drug	Tucatinib	Drug Info
Crosstalk ID: M6ACROT02231		Crosstalk Info
Epigenetic Regulator	Cysteine methyltransferase DNMT3A (DNMT3A)
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	DNA modification → m6A
Disease	Breast cancer	Disease Info
Drug	Trastuzumab	Drug Info
Crosstalk ID: M6ACROT02236		Crosstalk Info
Epigenetic Regulator	Cysteine methyltransferase DNMT3A (DNMT3A)
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	DNA modification → m6A
Disease	Breast cancer	Disease Info
Drug	Pertuzumab	Drug Info
Crosstalk ID: M6ACROT02244		Crosstalk Info
Epigenetic Regulator	Cysteine methyltransferase DNMT3A (DNMT3A)
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	DNA modification → m6A
Disease	Breast cancer	Disease Info
Drug	Tucatinib	Drug Info
Crosstalk ID: M6ACROT02255		Crosstalk Info
Epigenetic Regulator	DNA (cytosine-5)-methyltransferase 1 (DNMT1)
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	DNA modification → m6A
Disease	Breast cancer	Disease Info
Drug	Trastuzumab	Drug Info
Crosstalk ID: M6ACROT02260		Crosstalk Info
Epigenetic Regulator	DNA (cytosine-5)-methyltransferase 1 (DNMT1)
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	DNA modification → m6A
Disease	Breast cancer	Disease Info
Drug	Pertuzumab	Drug Info
Crosstalk ID: M6ACROT02268		Crosstalk Info
Epigenetic Regulator	DNA (cytosine-5)-methyltransferase 1 (DNMT1)
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	DNA modification → m6A
Disease	Breast cancer	Disease Info
Drug	Tucatinib	Drug Info

m6A Target: Solute carrier family 40 member 1 (FPN1)

Target Gene

In total 9 item(s) under this m6A target
Crosstalk ID: M6ACROT02208		Crosstalk Info
Epigenetic Regulator	DNA (cytosine-5)-methyltransferase 3B (DNMT3B)
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	DNA modification → m6A
Disease	Breast cancer	Disease Info
Drug	Trastuzumab	Drug Info
Crosstalk ID: M6ACROT02213		Crosstalk Info
Epigenetic Regulator	DNA (cytosine-5)-methyltransferase 3B (DNMT3B)
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	DNA modification → m6A
Disease	Breast cancer	Disease Info
Drug	Pertuzumab	Drug Info
Crosstalk ID: M6ACROT02221		Crosstalk Info
Epigenetic Regulator	DNA (cytosine-5)-methyltransferase 3B (DNMT3B)
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	DNA modification → m6A
Disease	Breast cancer	Disease Info
Drug	Tucatinib	Drug Info
Crosstalk ID: M6ACROT02232		Crosstalk Info
Epigenetic Regulator	Cysteine methyltransferase DNMT3A (DNMT3A)
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	DNA modification → m6A
Disease	Breast cancer	Disease Info
Drug	Trastuzumab	Drug Info
Crosstalk ID: M6ACROT02237		Crosstalk Info
Epigenetic Regulator	Cysteine methyltransferase DNMT3A (DNMT3A)
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	DNA modification → m6A
Disease	Breast cancer	Disease Info
Drug	Pertuzumab	Drug Info
Crosstalk ID: M6ACROT02245		Crosstalk Info
Epigenetic Regulator	Cysteine methyltransferase DNMT3A (DNMT3A)
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	DNA modification → m6A
Disease	Breast cancer	Disease Info
Drug	Tucatinib	Drug Info
Crosstalk ID: M6ACROT02256		Crosstalk Info
Epigenetic Regulator	DNA (cytosine-5)-methyltransferase 1 (DNMT1)
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	DNA modification → m6A
Disease	Breast cancer	Disease Info
Drug	Trastuzumab	Drug Info
Crosstalk ID: M6ACROT02261		Crosstalk Info
Epigenetic Regulator	DNA (cytosine-5)-methyltransferase 1 (DNMT1)
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	DNA modification → m6A
Disease	Breast cancer	Disease Info
Drug	Pertuzumab	Drug Info
Crosstalk ID: M6ACROT02269		Crosstalk Info
Epigenetic Regulator	DNA (cytosine-5)-methyltransferase 1 (DNMT1)
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	DNA modification → m6A
Disease	Breast cancer	Disease Info
Drug	Tucatinib	Drug Info

m6A Target: Fibroblast growth factor receptor 4 (FGFR4)

Target Gene

In total 9 item(s) under this m6A target
Crosstalk ID: M6ACROT02209		Crosstalk Info
Epigenetic Regulator	DNA (cytosine-5)-methyltransferase 3B (DNMT3B)
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	DNA modification → m6A
Disease	Breast cancer	Disease Info
Drug	Pertuzumab	Drug Info
Crosstalk ID: M6ACROT02215		Crosstalk Info
Epigenetic Regulator	DNA (cytosine-5)-methyltransferase 3B (DNMT3B)
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	DNA modification → m6A
Disease	Breast cancer	Disease Info
Drug	Tucatinib	Drug Info
Crosstalk ID: M6ACROT02222		Crosstalk Info
Epigenetic Regulator	DNA (cytosine-5)-methyltransferase 3B (DNMT3B)
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	DNA modification → m6A
Disease	Breast cancer	Disease Info
Drug	Trastuzumab	Drug Info
Crosstalk ID: M6ACROT02233		Crosstalk Info
Epigenetic Regulator	Cysteine methyltransferase DNMT3A (DNMT3A)
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	DNA modification → m6A
Disease	Breast cancer	Disease Info
Drug	Pertuzumab	Drug Info
Crosstalk ID: M6ACROT02239		Crosstalk Info
Epigenetic Regulator	Cysteine methyltransferase DNMT3A (DNMT3A)
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	DNA modification → m6A
Disease	Breast cancer	Disease Info
Drug	Tucatinib	Drug Info
Crosstalk ID: M6ACROT02246		Crosstalk Info
Epigenetic Regulator	Cysteine methyltransferase DNMT3A (DNMT3A)
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	DNA modification → m6A
Disease	Breast cancer	Disease Info
Drug	Trastuzumab	Drug Info
Crosstalk ID: M6ACROT02257		Crosstalk Info
Epigenetic Regulator	DNA (cytosine-5)-methyltransferase 1 (DNMT1)
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	DNA modification → m6A
Disease	Breast cancer	Disease Info
Drug	Pertuzumab	Drug Info
Crosstalk ID: M6ACROT02263		Crosstalk Info
Epigenetic Regulator	DNA (cytosine-5)-methyltransferase 1 (DNMT1)
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	DNA modification → m6A
Disease	Breast cancer	Disease Info
Drug	Tucatinib	Drug Info
Crosstalk ID: M6ACROT02270		Crosstalk Info
Epigenetic Regulator	DNA (cytosine-5)-methyltransferase 1 (DNMT1)
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	DNA modification → m6A
Disease	Breast cancer	Disease Info
Drug	Trastuzumab	Drug Info

m6A Target: Glycogen synthase kinase-3 beta (GSK3Beta/GSK3B)

Target Gene

In total 9 item(s) under this m6A target
Crosstalk ID: M6ACROT02210		Crosstalk Info
Epigenetic Regulator	DNA (cytosine-5)-methyltransferase 3B (DNMT3B)
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	DNA modification → m6A
Disease	Breast cancer	Disease Info
Drug	Pertuzumab	Drug Info
Crosstalk ID: M6ACROT02218		Crosstalk Info
Epigenetic Regulator	DNA (cytosine-5)-methyltransferase 3B (DNMT3B)
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	DNA modification → m6A
Disease	Breast cancer	Disease Info
Drug	Tucatinib	Drug Info
Crosstalk ID: M6ACROT02223		Crosstalk Info
Epigenetic Regulator	DNA (cytosine-5)-methyltransferase 3B (DNMT3B)
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	DNA modification → m6A
Disease	Breast cancer	Disease Info
Drug	Trastuzumab	Drug Info
Crosstalk ID: M6ACROT02234		Crosstalk Info
Epigenetic Regulator	Cysteine methyltransferase DNMT3A (DNMT3A)
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	DNA modification → m6A
Disease	Breast cancer	Disease Info
Drug	Pertuzumab	Drug Info
Crosstalk ID: M6ACROT02242		Crosstalk Info
Epigenetic Regulator	Cysteine methyltransferase DNMT3A (DNMT3A)
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	DNA modification → m6A
Disease	Breast cancer	Disease Info
Drug	Tucatinib	Drug Info
Crosstalk ID: M6ACROT02247		Crosstalk Info
Epigenetic Regulator	Cysteine methyltransferase DNMT3A (DNMT3A)
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	DNA modification → m6A
Disease	Breast cancer	Disease Info
Drug	Trastuzumab	Drug Info
Crosstalk ID: M6ACROT02258		Crosstalk Info
Epigenetic Regulator	DNA (cytosine-5)-methyltransferase 1 (DNMT1)
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	DNA modification → m6A
Disease	Breast cancer	Disease Info
Drug	Pertuzumab	Drug Info
Crosstalk ID: M6ACROT02266		Crosstalk Info
Epigenetic Regulator	DNA (cytosine-5)-methyltransferase 1 (DNMT1)
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	DNA modification → m6A
Disease	Breast cancer	Disease Info
Drug	Tucatinib	Drug Info
Crosstalk ID: M6ACROT02271		Crosstalk Info
Epigenetic Regulator	DNA (cytosine-5)-methyltransferase 1 (DNMT1)
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	DNA modification → m6A
Disease	Breast cancer	Disease Info
Drug	Trastuzumab	Drug Info

m6A Target: Transcription factor E2F8 (E2F8)

Target Gene

In total 9 item(s) under this m6A target
Crosstalk ID: M6ACROT02214		Crosstalk Info
Epigenetic Regulator	DNA (cytosine-5)-methyltransferase 3B (DNMT3B)
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	DNA modification → m6A
Disease	Breast cancer	Disease Info
Drug	Olaparib	Drug Info
Crosstalk ID: M6ACROT02216		Crosstalk Info
Epigenetic Regulator	DNA (cytosine-5)-methyltransferase 3B (DNMT3B)
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	DNA modification → m6A
Disease	Breast cancer	Disease Info
Drug	Cisplatin	Drug Info
Crosstalk ID: M6ACROT02217		Crosstalk Info
Epigenetic Regulator	DNA (cytosine-5)-methyltransferase 3B (DNMT3B)
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	DNA modification → m6A
Disease	Breast cancer	Disease Info
Drug	Adriamycin	Drug Info
Crosstalk ID: M6ACROT02238		Crosstalk Info
Epigenetic Regulator	Cysteine methyltransferase DNMT3A (DNMT3A)
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	DNA modification → m6A
Disease	Breast cancer	Disease Info
Drug	Olaparib	Drug Info
Crosstalk ID: M6ACROT02240		Crosstalk Info
Epigenetic Regulator	Cysteine methyltransferase DNMT3A (DNMT3A)
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	DNA modification → m6A
Disease	Breast cancer	Disease Info
Drug	Cisplatin	Drug Info
Crosstalk ID: M6ACROT02241		Crosstalk Info
Epigenetic Regulator	Cysteine methyltransferase DNMT3A (DNMT3A)
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	DNA modification → m6A
Disease	Breast cancer	Disease Info
Drug	Adriamycin	Drug Info
Crosstalk ID: M6ACROT02262		Crosstalk Info
Epigenetic Regulator	DNA (cytosine-5)-methyltransferase 1 (DNMT1)
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	DNA modification → m6A
Disease	Breast cancer	Disease Info
Drug	Olaparib	Drug Info
Crosstalk ID: M6ACROT02264		Crosstalk Info
Epigenetic Regulator	DNA (cytosine-5)-methyltransferase 1 (DNMT1)
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	DNA modification → m6A
Disease	Breast cancer	Disease Info
Drug	Cisplatin	Drug Info
Crosstalk ID: M6ACROT02265		Crosstalk Info
Epigenetic Regulator	DNA (cytosine-5)-methyltransferase 1 (DNMT1)
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	DNA modification → m6A
Disease	Breast cancer	Disease Info
Drug	Adriamycin	Drug Info

m6A Target: Transmembrane protein 127 (TMEM127)

Target Gene

In total 3 item(s) under this m6A target
Crosstalk ID: M6ACROT02224		Crosstalk Info
Epigenetic Regulator	DNA (cytosine-5)-methyltransferase 3B (DNMT3B)
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	DNA modification → m6A
Disease	Breast cancer	Disease Info
Drug	Rapamycin	Drug Info
Crosstalk ID: M6ACROT02248		Crosstalk Info
Epigenetic Regulator	Cysteine methyltransferase DNMT3A (DNMT3A)
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	DNA modification → m6A
Disease	Breast cancer	Disease Info
Drug	Rapamycin	Drug Info
Crosstalk ID: M6ACROT02272		Crosstalk Info
Epigenetic Regulator	DNA (cytosine-5)-methyltransferase 1 (DNMT1)
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	DNA modification → m6A
Disease	Breast cancer	Disease Info
Drug	Rapamycin	Drug Info

m6A Target: Calcium-binding and coiled-coil domain-containing protein 1 (CALCOCO1)

Target Gene

In total 6 item(s) under this m6A target
Crosstalk ID: M6ACROT02225		Crosstalk Info
Epigenetic Regulator	DNA (cytosine-5)-methyltransferase 3B (DNMT3B)
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	DNA modification → m6A
Disease	Breast cancer	Disease Info
Drug	Paclitaxel	Drug Info
Crosstalk ID: M6ACROT02249		Crosstalk Info
Epigenetic Regulator	Cysteine methyltransferase DNMT3A (DNMT3A)
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	DNA modification → m6A
Disease	Breast cancer	Disease Info
Drug	Paclitaxel	Drug Info
Crosstalk ID: M6ACROT02273		Crosstalk Info
Epigenetic Regulator	DNA (cytosine-5)-methyltransferase 1 (DNMT1)
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	DNA modification → m6A
Disease	Breast cancer	Disease Info
Drug	Paclitaxel	Drug Info
Crosstalk ID: M6ACROT05976		Crosstalk Info
Epigenetic Regulator	DNA (cytosine-5)-methyltransferase 3B (DNMT3B)
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	DNA modification → m6A
Disease	Breast cancer	Disease Info
Drug	STM2457	Drug Info
Crosstalk ID: M6ACROT05978		Crosstalk Info
Epigenetic Regulator	Cysteine methyltransferase DNMT3A (DNMT3A)
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	DNA modification → m6A
Disease	Breast cancer	Disease Info
Drug	STM2457	Drug Info
Crosstalk ID: M6ACROT05980		Crosstalk Info
Epigenetic Regulator	DNA (cytosine-5)-methyltransferase 1 (DNMT1)
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	DNA modification → m6A
Disease	Breast cancer	Disease Info
Drug	STM2457	Drug Info

m6A Target: Sequestosome-1 (SQSTM1)

Target Gene

In total 6 item(s) under this m6A target
Crosstalk ID: M6ACROT02226		Crosstalk Info
Epigenetic Regulator	DNA (cytosine-5)-methyltransferase 3B (DNMT3B)
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	DNA modification → m6A
Disease	Breast cancer	Disease Info
Drug	Paclitaxel	Drug Info
Crosstalk ID: M6ACROT02250		Crosstalk Info
Epigenetic Regulator	Cysteine methyltransferase DNMT3A (DNMT3A)
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	DNA modification → m6A
Disease	Breast cancer	Disease Info
Drug	Paclitaxel	Drug Info
Crosstalk ID: M6ACROT02274		Crosstalk Info
Epigenetic Regulator	DNA (cytosine-5)-methyltransferase 1 (DNMT1)
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	DNA modification → m6A
Disease	Breast cancer	Disease Info
Drug	Paclitaxel	Drug Info
Crosstalk ID: M6ACROT05977		Crosstalk Info
Epigenetic Regulator	DNA (cytosine-5)-methyltransferase 3B (DNMT3B)
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	DNA modification → m6A
Disease	Breast cancer	Disease Info
Drug	STM2457	Drug Info
Crosstalk ID: M6ACROT05979		Crosstalk Info
Epigenetic Regulator	Cysteine methyltransferase DNMT3A (DNMT3A)
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	DNA modification → m6A
Disease	Breast cancer	Disease Info
Drug	STM2457	Drug Info
Crosstalk ID: M6ACROT05981		Crosstalk Info
Epigenetic Regulator	DNA (cytosine-5)-methyltransferase 1 (DNMT1)
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	DNA modification → m6A
Disease	Breast cancer	Disease Info
Drug	STM2457	Drug Info

m6A Target: DNA (cytosine-5)-methyltransferase 1 (DNMT1)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT06014		Crosstalk Info
Epigenetic Regulator	DNA (cytosine-5)-methyltransferase 1 (DNMT1)
Regulated Target	Eomesodermin homolog (EOMES)
Crosstalk relationship	m6A → DNA modification

m6A Target: Insulin receptor (INSR)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT06016		Crosstalk Info
Epigenetic Regulator	DNA (cytosine-5)-methyltransferase 1 (DNMT1)
Regulated Target	Insulin receptor (INSR)
Crosstalk relationship	m6A → DNA modification

m6A Target: Mothers against decapentaplegic homolog 3 (SMAD3)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT06018		Crosstalk Info
Epigenetic Regulator	DNA (cytosine-5)-methyltransferase 1 (DNMT1)
Regulated Target	Mothers against decapentaplegic homolog 3 (SMAD3)
Crosstalk relationship	m6A → DNA modification

Histone modification

m6A Target: Phosphoprotein associated with glycosphingolipid-enriched microdomains 1 (CBP)

Target Gene

In total 3 item(s) under this m6A target
Crosstalk ID: M6ACROT03007		Crosstalk Info
Epigenetic Regulator	CREB-binding protein (CREBBP)
Regulated Target	Histone H3 lysine 27 acetylation (H3K27ac)
Crosstalk relationship	m6A → Histone modification
Crosstalk ID: M6ACROT03009		Crosstalk Info
Epigenetic Regulator	CREB-binding protein (CREBBP)
Regulated Target	Histone H3 lysine 4 trimethylation (H3K4me3)
Crosstalk relationship	m6A → Histone modification
Crosstalk ID: M6ACROT03011		Crosstalk Info
Epigenetic Regulator	CREB-binding protein (CREBBP)
Regulated Target	Histone H3 lysine 27 trimethylation (H3K27me3)
Crosstalk relationship	m6A → Histone modification

m6A Target: Histone acetyltransferase p300 (P300)

Target Gene

In total 3 item(s) under this m6A target
Crosstalk ID: M6ACROT03008		Crosstalk Info
Epigenetic Regulator	Histone acetyltransferase p300 (P300)
Regulated Target	Histone H3 lysine 27 acetylation (H3K27ac)
Crosstalk relationship	m6A → Histone modification
Crosstalk ID: M6ACROT03010		Crosstalk Info
Epigenetic Regulator	Histone acetyltransferase p300 (P300)
Regulated Target	Histone H3 lysine 4 trimethylation (H3K4me3)
Crosstalk relationship	m6A → Histone modification
Crosstalk ID: M6ACROT03012		Crosstalk Info
Epigenetic Regulator	Histone acetyltransferase p300 (P300)
Regulated Target	Histone H3 lysine 27 trimethylation (H3K27me3)
Crosstalk relationship	m6A → Histone modification

m6A Target: Lysine-specific demethylase 6B (KDM6B)

Target Gene

In total 2 item(s) under this m6A target
Crosstalk ID: M6ACROT03016		Crosstalk Info
Epigenetic Regulator	Lysine-specific demethylase 6B (KDM6B)
Regulated Target	Histone H3 lysine 27 trimethylation (H3K27me3)
Crosstalk relationship	m6A → Histone modification
Disease	Inflammatory response	Disease Info
Crosstalk ID: M6ACROT05997		Crosstalk Info
Epigenetic Regulator	Lysine-specific demethylase 6B (KDM6B)
Regulated Target	Histone H3 lysine 27 trimethylation (H3K27me3)
Crosstalk relationship	m6A → Histone modification
Disease	Inflammatory response	Disease Info

m6A Target: Interleukin-6 (IL-6)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT03019		Crosstalk Info
Epigenetic Regulator	Lysine-specific demethylase 6B (KDM6B)
Regulated Target	Histone H3 lysine 27 trimethylation (H3K27me3)
Crosstalk relationship	Histone modification → m6A
Disease	Inflammatory response	Disease Info

m6A Target: Histone-lysine N-methyltransferase SETD1A (SETD1A)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT03027		Crosstalk Info
Epigenetic Regulator	Histone-lysine N-methyltransferase SETD1A (SETD1A)
Regulated Target	Histone H3 lysine 4 trimethylation (H3K4me3)
Crosstalk relationship	m6A → Histone modification

m6A Target: Histone-lysine N-methyltransferase SETD1B (SETD1B)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT03028		Crosstalk Info
Epigenetic Regulator	Histone-lysine N-methyltransferase SETD1B (SETD1B)
Regulated Target	Histone H3 lysine 4 trimethylation (H3K4me3)
Crosstalk relationship	m6A → Histone modification

m6A Target: Histone-lysine N-methyltransferase 2D (KMT2D)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT03029		Crosstalk Info
Epigenetic Regulator	Histone-lysine N-methyltransferase 2D (KMT2D)
Regulated Target	Histone H3 lysine 4 trimethylation (H3K4me3)
Crosstalk relationship	m6A → Histone modification

m6A Target: Transcription factor SOX-4 (SOX4)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT03036		Crosstalk Info
Epigenetic Regulator	Lysine-specific demethylase 5C (KDM5C)
Regulated Target	Histone H3 lysine 4 trimethylation (H3K4me3)
Crosstalk relationship	Histone modification → m6A
Disease	Colorectal cancer	Disease Info

m6A Target: Protocadherin Fat 4 (FAT4)

Target Gene

In total 2 item(s) under this m6A target
Crosstalk ID: M6ACROT03051		Crosstalk Info
Epigenetic Regulator	Histone Deacetylase (HDAC)
Regulated Target	Histone H3 lysine 27 acetylation (H3K27ac)
Crosstalk relationship	Histone modification → m6A
Disease	Melanoma of uvea	Disease Info
Crosstalk ID: M6ACROT03052		Crosstalk Info
Epigenetic Regulator	Histone Deacetylase (HDAC)
Regulated Target	Histone H3 lysine 9 acetylation (H3K9Ac)
Crosstalk relationship	Histone modification → m6A
Disease	Melanoma of uvea	Disease Info

m6A Target: HOX transcript antisense RNA (HOTAIR)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT03063		Crosstalk Info
Epigenetic Regulator	Lysine-specific histone demethylase 1A (KDM1A)
Regulated Target	Histone H3 lysine 4 monomethylation (H3K4me1)
Crosstalk relationship	m6A → Histone modification
Disease	Disorders due to use of opioids	Disease Info
Drug	MM-102	Drug Info

m6A Target: long intergenic non-protein coding RNA 2747 (LINC02747)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT03064		Crosstalk Info
Epigenetic Regulator	Lysine-specific demethylase 5B (KDM5B)
Regulated Target	Histone H3 lysine 4 trimethylation (H3K4me3)
Crosstalk relationship	Histone modification → m6A
Disease	Non-small cell lung cancer	Disease Info

m6A Target: pri-rRNA

Target Gene

In total 2 item(s) under this m6A target
Crosstalk ID: M6ACROT03098		Crosstalk Info
Epigenetic Regulator	Histone-lysine N-methyltransferase SUV39H1 (SUV39H1)
Regulated Target	Histone H3 lysine 9 trimethylation (H3K9me3)
Crosstalk relationship	m6A → Histone modification
Crosstalk ID: M6ACROT03099		Crosstalk Info
Epigenetic Regulator	Histone-lysine N-methyltransferase SUV39H2 (SUV39H2)
Regulated Target	Histone H3 lysine 9 trimethylation (H3K9me3)
Crosstalk relationship	m6A → Histone modification

m6A Target: Metastasis associated lung adenocarcinoma transcript 1 (MALAT1)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT03116		Crosstalk Info
Epigenetic Regulator	Lysine-specific demethylase 2A (KDM2A)
Crosstalk relationship	m6A → Histone modification
Disease	Oral squamous cell carcinoma	Disease Info

m6A Target: Transcriptional coactivator YAP1 (YAP1)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT03139		Crosstalk Info
Epigenetic Regulator	Lysine-specific histone demethylase 1A (KDM1A)
Regulated Target	Histone H3 lysine 4 dimethylation (H3K4me2)
Crosstalk relationship	Histone modification → m6A
Disease	Triple-negative breast cancer	Disease Info

m6A Target: Ankyrin repeat domain-containing protein 22 (ANKRD22)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT03152		Crosstalk Info
Regulated Target	Histone H3 lysine 27 acetylation (H3K27ac)
Crosstalk relationship	Histone modification → m6A
Disease	Nasopharyngeal carcinoma	Disease Info

m6A Target: Amino acid transporter heavy chain SLC3A2 (SLC3A2)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT03156		Crosstalk Info
Epigenetic Regulator	Bifunctional arginine demethylase and lysyl-hydroxylase JMJD6 (JMJD6)
Regulated Target	Histone H4 arginine 3 symmetric dimethylation (H4R3me2a)
Crosstalk relationship	Histone modification → m6A
Disease	Lung cancer	Disease Info

m6A Target: Cyclic AMP-dependent transcription factor ATF-5 (ATF5)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT03157		Crosstalk Info
Regulated Target	Histone H3 lysine 18 lactylation (H3K18la)
Crosstalk relationship	Histone modification → m6A
Disease	Gastric cancer	Disease Info

m6A Target: Histone deacetylase 3 (HDAC3)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT03206		Crosstalk Info
Epigenetic Regulator	Histone deacetylase 3 (HDAC3)
Crosstalk relationship	m6A → Histone modification
Disease	Acute ischemic stroke	Disease Info

m6A Target: Homeobox protein Hox-A13 (HOXA13)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT03229		Crosstalk Info
Epigenetic Regulator	PHD finger protein 20 (PHF20)
Regulated Target	Histone H3 lysine 4 trimethylation (H3K4me3)
Crosstalk relationship	Histone modification → m6A

m6A Target: microRNA 375 (MIR375)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT03276		Crosstalk Info
Epigenetic Regulator	Lysine-specific demethylase 5C (KDM5C)
Regulated Target	Histone H3 lysine 4 trimethylation (H3K4me3)
Crosstalk relationship	Histone modification → m6A
Disease	Colorectal cancer	Disease Info

m6A Target: X inactive specific transcript (XIST)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT03277		Crosstalk Info
Epigenetic Regulator	Lysine-specific demethylase 5C (KDM5C)
Regulated Target	Histone H3 lysine 4 trimethylation (H3K4me3)
Crosstalk relationship	Histone modification → m6A
Disease	Colorectal cancer	Disease Info

m6A Target: Interferon gamma (IFN-gamma)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT03278		Crosstalk Info
Epigenetic Regulator	Lysine-specific demethylase 5C (KDM5C)
Regulated Target	Histone H3 lysine 4 trimethylation (H3K4me3)
Crosstalk relationship	Histone modification → m6A
Disease	Colorectal cancer	Disease Info

m6A Target: C-X-C motif chemokine 9 (Cxcl9)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT03279		Crosstalk Info
Epigenetic Regulator	Lysine-specific demethylase 5C (KDM5C)
Regulated Target	Histone H3 lysine 4 trimethylation (H3K4me3)
Crosstalk relationship	Histone modification → m6A
Disease	Colorectal cancer	Disease Info

m6A Target: C-X-C motif chemokine 10 (Cxcl10)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT03280		Crosstalk Info
Epigenetic Regulator	Lysine-specific demethylase 5C (KDM5C)
Regulated Target	Histone H3 lysine 4 trimethylation (H3K4me3)
Crosstalk relationship	Histone modification → m6A
Disease	Colorectal cancer	Disease Info

m6A Target: Transcription factor ISGF-3 components p91/p84 (Stat1)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT03281		Crosstalk Info
Epigenetic Regulator	Lysine-specific demethylase 5C (KDM5C)
Regulated Target	Histone H3 lysine 4 trimethylation (H3K4me3)
Crosstalk relationship	Histone modification → m6A
Disease	Colorectal cancer	Disease Info

m6A Target: Interferon regulatory factor 1 (Irf1)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT03282		Crosstalk Info
Epigenetic Regulator	Lysine-specific demethylase 5C (KDM5C)
Regulated Target	Histone H3 lysine 4 trimethylation (H3K4me3)
Crosstalk relationship	Histone modification → m6A
Disease	Colorectal cancer	Disease Info

m6A Target: Arrestin domain-containing protein 4 (ARRDC4)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT03283		Crosstalk Info
Epigenetic Regulator	Lysine-specific demethylase 5C (KDM5C)
Regulated Target	Histone H3 lysine 4 trimethylation (H3K4me3)
Crosstalk relationship	Histone modification → m6A
Disease	Colorectal cancer	Disease Info

m6A Target: Krueppel-like factor 4 (KLF4)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT03284		Crosstalk Info
Epigenetic Regulator	Lysine-specific demethylase 5C (KDM5C)
Regulated Target	Histone H3 lysine 4 trimethylation (H3K4me3)
Crosstalk relationship	Histone modification → m6A
Disease	Colorectal cancer	Disease Info

m6A Target: Polyamine-transporting ATPase 13A3 (ATP13A3)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT03285		Crosstalk Info
Epigenetic Regulator	Lysine-specific demethylase 5C (KDM5C)
Regulated Target	Histone H3 lysine 4 trimethylation (H3K4me3)
Crosstalk relationship	Histone modification → m6A
Disease	Colorectal cancer	Disease Info

m6A Target: pri-miR-17

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT03286		Crosstalk Info
Epigenetic Regulator	Lysine-specific demethylase 5C (KDM5C)
Regulated Target	Histone H3 lysine 4 trimethylation (H3K4me3)
Crosstalk relationship	Histone modification → m6A
Disease	Colorectal cancer	Disease Info
Drug	Fluorouracil	Drug Info

m6A Target: BET1-like protein (BET1L)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT03287		Crosstalk Info
Epigenetic Regulator	Lysine-specific demethylase 5C (KDM5C)
Regulated Target	Histone H3 lysine 4 trimethylation (H3K4me3)
Crosstalk relationship	Histone modification → m6A
Disease	Colorectal cancer	Disease Info

m6A Target: JmjC domain-containing protein 8 (JMJD8)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT03288		Crosstalk Info
Epigenetic Regulator	Lysine-specific demethylase 5C (KDM5C)
Regulated Target	Histone H3 lysine 4 trimethylation (H3K4me3)
Crosstalk relationship	Histone modification → m6A
Disease	Colorectal cancer	Disease Info

m6A Target: Zinc finger protein PLAGL2 (PLAGL2)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT03307		Crosstalk Info
Epigenetic Regulator	Lysine-specific demethylase 5B (KDM5B)
Regulated Target	Histone H3 lysine 4 trimethylation (H3K4me3)
Crosstalk relationship	Histone modification → m6A
Disease	Non-small cell lung cancer	Disease Info

m6A Target: Macrophage colony-stimulating factor 1 receptor (CSF1R)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT03308		Crosstalk Info
Epigenetic Regulator	Lysine-specific demethylase 5B (KDM5B)
Regulated Target	Histone H3 lysine 4 trimethylation (H3K4me3)
Crosstalk relationship	Histone modification → m6A
Disease	Non-small cell lung cancer	Disease Info

m6A Target: pri-miR-93-5p

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT03309		Crosstalk Info
Epigenetic Regulator	Lysine-specific demethylase 5B (KDM5B)
Regulated Target	Histone H3 lysine 4 trimethylation (H3K4me3)
Crosstalk relationship	Histone modification → m6A
Disease	Non-small cell lung cancer	Disease Info

m6A Target: hsa-miR-30c-1-3p

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT03493		Crosstalk Info
Epigenetic Regulator	Bifunctional arginine demethylase and lysyl-hydroxylase JMJD6 (JMJD6)
Regulated Target	Histone H4 arginine 3 symmetric dimethylation (H4R3me2a)
Crosstalk relationship	Histone modification → m6A
Disease	Lung cancer	Disease Info

m6A Target: Long intergenic non-protein coding RNA 1320 (LINC01320)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT03494		Crosstalk Info
Regulated Target	Histone H3 lysine 18 lactylation (H3K18la)
Crosstalk relationship	Histone modification → m6A
Disease	Gastric cancer	Disease Info

m6A Target: Circ_ORC5

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT03495		Crosstalk Info
Regulated Target	Histone H3 lysine 18 lactylation (H3K18la)
Crosstalk relationship	Histone modification → m6A
Disease	Gastric cancer	Disease Info

m6A Target: hsa-miR-30c-2-3p

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT03496		Crosstalk Info
Regulated Target	Histone H3 lysine 18 lactylation (H3K18la)
Crosstalk relationship	Histone modification → m6A
Disease	Gastric cancer	Disease Info

m6A Target: Proline-rich AKT1 substrate 1 (AKT1S1)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT03497		Crosstalk Info
Regulated Target	Histone H3 lysine 18 lactylation (H3K18la)
Crosstalk relationship	Histone modification → m6A
Disease	Gastric cancer	Disease Info

m6A Target: PI3-kinase subunit alpha (PI3k/PIK3CA)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT03498		Crosstalk Info
Regulated Target	Histone H3 lysine 18 lactylation (H3K18la)
Crosstalk relationship	Histone modification → m6A
Disease	Gastric cancer	Disease Info

m6A Target: RAC-alpha serine/threonine-protein kinase (AKT1)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT03499		Crosstalk Info
Regulated Target	Histone H3 lysine 18 lactylation (H3K18la)
Crosstalk relationship	Histone modification → m6A
Disease	Gastric cancer	Disease Info

m6A Target: Serine/threonine-protein kinase mTOR (MTOR)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT03500		Crosstalk Info
Regulated Target	Histone H3 lysine 18 lactylation (H3K18la)
Crosstalk relationship	Histone modification → m6A
Disease	Gastric cancer	Disease Info

m6A Target: Mutated in multiple advanced cancers 1 (PTEN)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT03501		Crosstalk Info
Regulated Target	Histone H3 lysine 18 lactylation (H3K18la)
Crosstalk relationship	Histone modification → m6A
Disease	Gastric cancer	Disease Info

m6A Target: Signal transducer and activator of transcription 3 (STAT3)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT03502		Crosstalk Info
Regulated Target	Histone H3 lysine 18 lactylation (H3K18la)
Crosstalk relationship	Histone modification → m6A
Disease	Gastric cancer	Disease Info

m6A Target: Interleukin-12 subunit beta (IL12B)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT06000		Crosstalk Info
Epigenetic Regulator	Lysine-specific demethylase 6B (KDM6B)
Regulated Target	Histone H3 lysine 27 trimethylation (H3K27me3)
Crosstalk relationship	Histone modification → m6A
Disease	Inflammatory response	Disease Info

Non-coding RNA

m6A Target: Circ_FUT8

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05121		Crosstalk Info
Epigenetic Regulator	hsa-miR-628-5p
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	ncRNA → m6A
Disease	Liver cancer	Disease Info

m6A Target: Hypoxia-inducible factor 1-alpha (HIF-1-Alpha/HIF1A)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05123		Crosstalk Info
Epigenetic Regulator	Urothelial cancer associated 1 (UCA1)
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	ncRNA → m6A
Disease	Psoriasis	Disease Info

m6A Target: NAD-dependent protein deacetylase sirtuin-1 (SIRT1)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05148		Crosstalk Info
Epigenetic Regulator	hsa-miR-103-3p
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	ncRNA → m6A
Disease	Osteoporosis	Disease Info

m6A Target: Hepatocyte nuclear factor 1-alpha (HNF1A/TCF1)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05149		Crosstalk Info
Epigenetic Regulator	hsa-miR-103-3p
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	ncRNA → m6A
Disease	Osteoporosis	Disease Info

m6A Target: Phospholipid hydroperoxide glutathione peroxidase GPX4 (GPX4)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05150		Crosstalk Info
Epigenetic Regulator	hsa-miR-103-3p
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	ncRNA → m6A
Disease	Osteoporosis	Disease Info

m6A Target: Nuclear factor of activated T-cells, cytoplasmic 1 (NFATC1)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05151		Crosstalk Info
Epigenetic Regulator	hsa-miR-103-3p
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	ncRNA → m6A
Disease	Osteoporosis	Disease Info

m6A Target: Solute carrier family 2, facilitated glucose transporter member 3 (SLC2A3)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05152		Crosstalk Info
Epigenetic Regulator	hsa-miR-103-3p
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	ncRNA → m6A
Disease	Osteoporosis	Disease Info

m6A Target: Protein disulfide-isomerase (P4HB)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05153		Crosstalk Info
Epigenetic Regulator	hsa-miR-103-3p
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	ncRNA → m6A
Disease	Osteoporosis	Disease Info
Drug	ICARIIN	Drug Info

m6A Target: Mitochondrial fission 1 protein (FIS1)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05160		Crosstalk Info
Epigenetic Regulator	Lnc-Gm10532
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	ncRNA → m6A
Disease	Cognitive impairment	Disease Info

m6A Target: C-X-C chemokine receptor type 4 (CXCR4)

Target Gene

In total 2 item(s) under this m6A target
Crosstalk ID: M6ACROT05173		Crosstalk Info
Epigenetic Regulator	hsa_circ_0125169 (Circ_METTL14(11)S)
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	ncRNA → m6A
Disease	Inflammatory response	Disease Info
Crosstalk ID: M6ACROT05352		Crosstalk Info
Epigenetic Regulator	Long intergenic non-protein coding RNA 942 (LINC00942)
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	ncRNA → m6A
Disease	Breast cancer	Disease Info

m6A Target: Ubiquitin carboxyl-terminal hydrolase 38 (USP38)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05174		Crosstalk Info
Epigenetic Regulator	hsa-miR-3165
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	ncRNA → m6A
Disease	Bladder cancer	Disease Info

m6A Target: Intraflagellar transport protein 80 homolog (IFT80)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05178		Crosstalk Info
Epigenetic Regulator	H2AZ2 pseudogene 1 (H2AZ2P1)
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	ncRNA → m6A
Disease	Head and neck squamous carcinoma	Disease Info

m6A Target: CCN family member 2 (CTGF)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05185		Crosstalk Info
Epigenetic Regulator	AI662270
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	ncRNA → m6A
Disease	Chronic kidney disease	Disease Info

m6A Target: Cytochrome P450 1B1 (CYP1B1)

Target Gene

In total 2 item(s) under this m6A target
Crosstalk ID: M6ACROT05193		Crosstalk Info
Epigenetic Regulator	piR-14633
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	ncRNA → m6A
Disease	Cervical cancer	Disease Info
Crosstalk ID: M6ACROT05353		Crosstalk Info
Epigenetic Regulator	Long intergenic non-protein coding RNA 942 (LINC00942)
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	ncRNA → m6A
Disease	Breast cancer	Disease Info

m6A Target: Pancreas/duodenum homeobox protein 1 (Pdx1)

Target Gene

In total 12 item(s) under this m6A target
Crosstalk ID: M6ACROT05194		Crosstalk Info
Epigenetic Regulator	hsa-miR-141
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	ncRNA → m6A
Drug	Bisphenol F	Drug Info
Crosstalk ID: M6ACROT05195		Crosstalk Info
Epigenetic Regulator	hsa-miR-200b
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	ncRNA → m6A
Drug	Bisphenol F	Drug Info
Crosstalk ID: M6ACROT05196		Crosstalk Info
Epigenetic Regulator	hsa-miR-200c
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	ncRNA → m6A
Drug	Bisphenol F	Drug Info
Crosstalk ID: M6ACROT05984		Crosstalk Info
Epigenetic Regulator	hsa-miR-141
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	ncRNA → m6A
Drug	4-(4-hydroxyphenyl)sulfonylphenol	Drug Info
Crosstalk ID: M6ACROT05985		Crosstalk Info
Epigenetic Regulator	hsa-miR-200b
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	ncRNA → m6A
Drug	4-(4-hydroxyphenyl)sulfonylphenol	Drug Info
Crosstalk ID: M6ACROT05986		Crosstalk Info
Epigenetic Regulator	hsa-miR-200c
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	ncRNA → m6A
Drug	4-(4-hydroxyphenyl)sulfonylphenol	Drug Info
Crosstalk ID: M6ACROT05987		Crosstalk Info
Epigenetic Regulator	hsa-miR-141
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	ncRNA → m6A
Drug	BPAF	Drug Info
Crosstalk ID: M6ACROT05988		Crosstalk Info
Epigenetic Regulator	hsa-miR-200b
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	ncRNA → m6A
Drug	BPAF	Drug Info
Crosstalk ID: M6ACROT05989		Crosstalk Info
Epigenetic Regulator	hsa-miR-200c
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	ncRNA → m6A
Drug	BPAF	Drug Info
Crosstalk ID: M6ACROT05990		Crosstalk Info
Epigenetic Regulator	hsa-miR-141
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	ncRNA → m6A
Drug	Bisphenol A	Drug Info
Crosstalk ID: M6ACROT05991		Crosstalk Info
Epigenetic Regulator	hsa-miR-200b
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	ncRNA → m6A
Drug	Bisphenol A	Drug Info
Crosstalk ID: M6ACROT05992		Crosstalk Info
Epigenetic Regulator	hsa-miR-200c
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	ncRNA → m6A
Drug	Bisphenol A	Drug Info

m6A Target: Ferroptosis suppressor protein 1 (AIFM2)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05202		Crosstalk Info
Epigenetic Regulator	hsa-miR-130a-3p
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	ncRNA → m6A
Disease	Esophageal cancer	Disease Info
Drug	Cisplatin	Drug Info

m6A Target: Signal transducer and activator of transcription 3 (STAT3)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05325		Crosstalk Info
Epigenetic Regulator	LOC10013.776 (AGAP2-AS1)
Regulated Target	Pre-mRNA-splicing regulator WTAP (WTAP)
Crosstalk relationship	ncRNA → m6A
Disease	Gastric cancer	Disease Info

m6A Target: NACHT, LRR and PYD domains-containing protein 3 (NLRP3)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05329		Crosstalk Info
Epigenetic Regulator	hsa-miR-26a-5p
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	ncRNA → m6A
Disease	Intervertebral disc degeneration	Disease Info

m6A Target: Aspartate--tRNA ligase, cytoplasmic (DARS)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05357		Crosstalk Info
Epigenetic Regulator	DARS1 antisense RNA 1 (DARS1-AS1)
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	ncRNA → m6A
Disease	Cervical cancer	Disease Info

m6A Target: Transcription factor SOX-9 (SOX9)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05368		Crosstalk Info
Epigenetic Regulator	Circ_FTO
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	ncRNA → m6A
Disease	Rheumatoid arthritis	Disease Info

m6A Target: microRNA 375 (MIR375)

Target Gene

In total 3 item(s) under this m6A target
Crosstalk ID: M6ACROT05410		Crosstalk Info
Epigenetic Regulator	MicroRNA 375 (MIR375)
Crosstalk relationship	m6A → ncRNA
Disease	Colorectal cancer	Disease Info
Crosstalk ID: M6ACROT05606		Crosstalk Info
Epigenetic Regulator	MicroRNA 375 (MIR375)
Regulated Target	Dexamethasone-induced Ras-related protein 1 (RASD1)
Crosstalk relationship	m6A → ncRNA
Disease	Injuries of spine or trunk	Disease Info
Crosstalk ID: M6ACROT05931		Crosstalk Info
Epigenetic Regulator	MicroRNA 375 (MIR375)
Regulated Target	Transcription factor SOX-12 (SOX12)
Crosstalk relationship	m6A → ncRNA
Disease	Breast cancer	Disease Info

m6A Target: X inactive specific transcript (XIST)

Target Gene

In total 2 item(s) under this m6A target
Crosstalk ID: M6ACROT05421		Crosstalk Info
Epigenetic Regulator	X inactive specific transcript (XIST)
Crosstalk relationship	m6A → ncRNA
Disease	Colorectal cancer	Disease Info
Crosstalk ID: M6ACROT05836		Crosstalk Info
Epigenetic Regulator	X inactive specific transcript (XIST)
Crosstalk relationship	m6A → ncRNA
Disease	Diffuse large B-cell lymphomas	Disease Info

m6A Target: LncRNA activating regulator of DKK1 (LNCAROD)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05426		Crosstalk Info
Epigenetic Regulator	LncRNA activating regulator of DKK1 (LNCAROD)
Regulated Target	Heat shock 70 kDa protein 1A (HSPA1A)
Crosstalk relationship	m6A → ncRNA
Disease	Head and neck squamous carcinoma	Disease Info

m6A Target: hsa-miR-146a-5p

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05431		Crosstalk Info
Epigenetic Regulator	hsa-miR-146a-5p
Crosstalk relationship	m6A → ncRNA
Disease	Breast cancer	Disease Info

m6A Target: hsa-miR-19a-3p

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05435		Crosstalk Info
Epigenetic Regulator	hsa-miR-19a-3p
Crosstalk relationship	m6A → ncRNA
Disease	Atherosclerosis	Disease Info

m6A Target: H19 imprinted maternally expressed transcript (H19)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05451		Crosstalk Info
Epigenetic Regulator	H19 imprinted maternally expressed transcript (H19)
Crosstalk relationship	m6A → ncRNA
Disease	Abnormalities of breathing	Disease Info

m6A Target: hsa_circ_0089552 (circ_NOTCH1)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05453		Crosstalk Info
Epigenetic Regulator	hsa_circ_0089552 (Circ_NOTCH1)
Regulated Target	Neurogenic locus notch homolog protein 1 (NOTCH1)
Crosstalk relationship	m6A → ncRNA
Disease	Non-small cell lung cancer	Disease Info

m6A Target: ZNFX1 antisense RNA 1 (ZFAS1)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05455		Crosstalk Info
Epigenetic Regulator	ZNFX1 antisense RNA 1 (ZFAS1)
Regulated Target	Ras-related protein Rab-22A (RAB22A)
Crosstalk relationship	m6A → ncRNA
Disease	Atherosclerosis	Disease Info

m6A Target: Circ_GFR-Alpha-1

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05491		Crosstalk Info
Epigenetic Regulator	Circ_GFR-Alpha-1
Regulated Target	MicroRNA 449a (MIR449A)
Crosstalk relationship	m6A → ncRNA
Disease	Female reproductive system disorders	Disease Info

m6A Target: Long intergenic non-protein coding RNA 1320 (LINC01320)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05499		Crosstalk Info
Epigenetic Regulator	Long intergenic non-protein coding RNA 1320 (LINC01320)
Regulated Target	hsa-miR-495-5p
Crosstalk relationship	m6A → ncRNA
Disease	Gastric cancer	Disease Info

m6A Target: microRNA 211 (MIR211)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05500		Crosstalk Info
Epigenetic Regulator	MicroRNA 211 (MIR211)
Regulated Target	Transcription factor 12 (TCF12)
Crosstalk relationship	m6A → ncRNA
Disease	Lymphoma	Disease Info

m6A Target: HLA complex group 11 (HCG11)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05523		Crosstalk Info
Epigenetic Regulator	HLA complex group 11 (HCG11)
Regulated Target	Serine/threonine-protein kinase LATS1 (LATS1)
Crosstalk relationship	m6A → ncRNA
Disease	Lung cancer	Disease Info

m6A Target: hsa_circ_0008399 (Circ_RBM3)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05531		Crosstalk Info
Epigenetic Regulator	hsa_circ_0008399 (Circ_RBM3)
Regulated Target	Pre-mRNA-splicing regulator WTAP (WTAP)
Crosstalk relationship	m6A → ncRNA
Disease	Bladder cancer	Disease Info
Drug	Cisplatin	Drug Info

m6A Target: Nuclear paraspeckle assembly transcript 1 (NEAT1)

Target Gene

In total 2 item(s) under this m6A target
Crosstalk ID: M6ACROT05540		Crosstalk Info
Epigenetic Regulator	Nuclear paraspeckle assembly transcript 1 (NEAT1)
Crosstalk relationship	m6A → ncRNA
Disease	Renal cell carcinoma	Disease Info
Crosstalk ID: M6ACROT05729		Crosstalk Info
Epigenetic Regulator	Nuclear paraspeckle assembly transcript 1 (NEAT1)
Regulated Target	Krueppel-like factor 4 (KLF4)
Crosstalk relationship	m6A → ncRNA
Disease	Coronary atherosclerosis	Disease Info

m6A Target: hsa-miR-380-3p

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05564		Crosstalk Info
Epigenetic Regulator	hsa-miR-380-3p
Regulated Target	Mutated in multiple advanced cancers 1 (PTEN)
Crosstalk relationship	m6A → ncRNA
Disease	Pancreatic cancer	Disease Info

m6A Target: hsa-miR-99a-5p

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05573		Crosstalk Info
Epigenetic Regulator	hsa-miR-99a-5p
Regulated Target	Tribbles homolog 2 (TRIB2)
Crosstalk relationship	m6A → ncRNA
Disease	Esophageal Squamous Cell Carcinoma	Disease Info

m6A Target: hsa-miR-30c-1-3p

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05578		Crosstalk Info
Epigenetic Regulator	hsa-miR-30c-1-3p
Regulated Target	MARCKS-related protein (MARCKSL1)
Crosstalk relationship	m6A → ncRNA
Disease	Lung cancer	Disease Info

m6A Target: Lnc_LSG1

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05590		Crosstalk Info
Epigenetic Regulator	Lnc_LSG1
Regulated Target	Epithelial splicing regulatory protein 2 (ESRP2)
Crosstalk relationship	m6A → ncRNA
Disease	Renal cell carcinoma	Disease Info

m6A Target: Circ_ORC5

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05598		Crosstalk Info
Epigenetic Regulator	Circ_ORC5
Regulated Target	hsa-miR-30c-2-3p
Crosstalk relationship	m6A → ncRNA
Disease	Gastric cancer	Disease Info

m6A Target: hsa-miR-30c-2-3p

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05599		Crosstalk Info
Epigenetic Regulator	hsa-miR-30c-2-3p
Regulated Target	Proline-rich AKT1 substrate 1 (AKT1S1)
Crosstalk relationship	m6A → ncRNA
Disease	Gastric cancer	Disease Info

m6A Target: Metastasis associated lung adenocarcinoma transcript 1 (MALAT1)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05624		Crosstalk Info
Epigenetic Regulator	Metastasis associated lung adenocarcinoma transcript 1 (MALAT1)
Regulated Target	hsa-miR-224-5p
Crosstalk relationship	m6A → ncRNA
Disease	Oral squamous cell carcinoma	Disease Info

m6A Target: pri-miR-873

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05666		Crosstalk Info
Epigenetic Regulator	pri-miR-873
Crosstalk relationship	m6A → ncRNA

m6A Target: TNF and HNRNPL related immunoregulatory long non-coding RNA (THRIL)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05725		Crosstalk Info
Epigenetic Regulator	TNF and HNRNPL related immunoregulatory long non-coding RNA (THRIL)
Crosstalk relationship	m6A → ncRNA
Disease	Injury of other or unspecified intrathoracic organs	Disease Info
Drug	LPS	Drug Info

m6A Target: miR-6858

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05734		Crosstalk Info
Epigenetic Regulator	miR-6858
Regulated Target	Gasdermin C (GSDMC)
Crosstalk relationship	m6A → ncRNA
Disease	Lichen planus	Disease Info

m6A Target: Long intergenic non-protein coding RNA 941 (LINC00941)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05735		Crosstalk Info
Epigenetic Regulator	Long intergenic non-protein coding RNA 941 (LINC00941)
Regulated Target	Insulin like growth factor 2 mRNA binding protein 2 (IGF2BP2)
Crosstalk relationship	m6A → ncRNA
Disease	Pancreatic cancer	Disease Info

m6A Target: microRNA 93 (MIR93)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05770		Crosstalk Info
Epigenetic Regulator	MicroRNA 93 (MIR93)
Regulated Target	Thioredoxin-interacting protein (TXNIP)
Crosstalk relationship	m6A → ncRNA
Disease	Non-small cell lung cancer	Disease Info

m6A Target: AC026356.1

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05773		Crosstalk Info
Epigenetic Regulator	AC026356.1
Crosstalk relationship	m6A → ncRNA
Disease	Lung cancer	Disease Info

m6A Target: hsa-miR-34a

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05804		Crosstalk Info
Epigenetic Regulator	MicroRNA 34a (MIR34A)
Regulated Target	NAD-dependent protein deacetylase sirtuin-1 (SIRT1)
Crosstalk relationship	m6A → ncRNA

m6A Target: OIP5 antisense RNA 1 (OIP5-AS1)

Target Gene

In total 2 item(s) under this m6A target
Crosstalk ID: M6ACROT05806		Crosstalk Info
Epigenetic Regulator	OIP5 antisense RNA 1 (OIP5-AS1)
Regulated Target	MicroRNA 98 (MIR98)
Crosstalk relationship	m6A → ncRNA
Disease	Papillary thyroid cancer	Disease Info
Crosstalk ID: M6ACROT05963		Crosstalk Info
Epigenetic Regulator	MicroRNA 98 (MIR98)
Regulated Target	A disintegrin and metalloproteinase with thrombospondin motifs 8 (ADAMTS8)
Crosstalk relationship	m6A → ncRNA
Disease	Papillary thyroid cancer	Disease Info

m6A Target: KCNQ1 opposite strand/antisense transcript 1 (KCNQ1OT1)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05813		Crosstalk Info
Epigenetic Regulator	KCNQ1 opposite strand/antisense transcript 1 (KCNQ1OT1)
Regulated Target	hsa-miR-7-5p
Crosstalk relationship	m6A → ncRNA
Drug	Doxorubicin	Drug Info

m6A Target: hsa-miR-21-5p

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05823		Crosstalk Info
Epigenetic Regulator	hsa-miR-21-5p
Regulated Target	Mothers against decapentaplegic homolog 3 (SMAD3)
Crosstalk relationship	m6A → ncRNA
Disease	Abortion	Disease Info

m6A Target: TRHDE antisense RNA 1 (TRHDE-AS1)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05832		Crosstalk Info
Epigenetic Regulator	TRHDE antisense RNA 1 (TRHDE-AS1)
Crosstalk relationship	m6A → ncRNA
Disease	Prostate cancer	Disease Info
Drug	Propofol	Drug Info

m6A Target: SREBF2 antisense RNA 1 (SREBF2-AS1)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05834		Crosstalk Info
Epigenetic Regulator	SREBF2 antisense RNA 1 (SREBF2-AS1)
Regulated Target	FMR1 autosomal homolog 1 (FXR1)
Crosstalk relationship	m6A → ncRNA
Disease	Acute myeloid leukaemia	Disease Info
Drug	Chidamide	Drug Info

m6A Target: Retinoic Acid Receptor Alpha-Retinoic Acid Receptor Alpha (PML-RARalpha)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05879		Crosstalk Info
Epigenetic Regulator	Metastasis associated lung adenocarcinoma transcript 1 (MALAT1)
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	ncRNA → m6A
Disease	Blood malignancies	Disease Info

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	Knockdown of METTL3 or METTL14 induced changes in mRNA m6A enrichment and altered mRNA expression of genes (e.g.,ADAM19) with critical biological functions inGSCs. Treatment with MA2, a chemical inhibitor of FTO, dramatically suppressed GSC-induced tumorigenesis and prolonged lifespan in GSC-grafted animals.	[31]
Compound Name	Tamoxifen	Approved
Synonyms	tamoxifen; 10540-29-1; trans-Tamoxifen; Crisafeno; Soltamox; Tamoxifene; Diemon; Tamoxifenum; Tamoxifeno; Tamizam; Istubol; Tamoxen; Citofen; Oncomox; Valodex; Retaxim; Tamoxifene [INN-French]; Tamoxifenum [INN-Latin]; Tamoxifeno [INN-Spanish]; Tamoxifen (Z); Tamoxifen and its salts; Tamoxifen [INN:BAN]; ICI-46474; ICI 47699; TRANS FORM OF TAMOXIFEN; CCRIS 3275; UNII-094ZI81Y45; HSDB 6782; CHEMBL83; EINECS 234-118-0; 1-p-beta-Dimethylaminoethoxyphenyl-trans-1,2-diphenylbut-1-ene; Citofen; Nourytam; Novaldex; Tamone; Tamoxifeno;Tamoxifenum; Tomaxithen; Gen-Tamoxifen; Istubal (TN); Nolvadex (TN); Nolvadex-D; Novo-Tamoxifen; Pms-Tamoxifen; Tamoplex (TN); Tamoxifen (INN); Tamoxifen (TN); Trans-Tamoxifen; Valodex (TN); TAMOXIFEN (TAMOXIFEN CITRATE (54965-24-1)); Trans-2-[4-(1,2-Diphenyl-1-butenyl)phenoxy]-N,N-dimethylethylamine; (Z)-1-(p-Dimethylaminoethoxyphenyl)-1,2-diphenyl-1-butene; (Z)-2-(4-(1,2-Diphenyl-1-butenyl)phenoxy)-N,N-dimethylethanamine; (Z)-2-(4-(1,2-diphenylbut-1-enyl)phenoxy)-N,N-dimethylethanamine; (Z)-2-(para-(1,2-Diphenyl-1-butenyl)phenoxy)-N,N-dimethylamine (IUPAC); (Z)-2-[4-(1,2)-DIPHENYL-1-BUTENYL)-PHENOXY]-N,N-DIMETHYLETHANAMINE; (Z)-2-[p-(1,2-Diphenyl-1-butenyl)phenoxy]-N,N-dimethylethylamine; 1-p-beta-Dimethylamino-ethoxyphenyl-trans-1,2-diphenylbut-1-ene; 1-para-beta-Dimethylaminoethoxyphenyl-trans-1,2-diphenylbut-1-ene; 2-[4-[(Z)-1,2-diphenylbut-1-enyl]phenoxy]-N,N-dimethylethanamine; 2-{4-[(1Z)-1,2-diphenylbut-1-en-1-yl]phenoxy}-N,N-dimethylethanamine; Tamoxifen (Hormonal therapy); [3H]tamoxifen Click to Show/Hide
External link	CID: 2733526 TTD: D07KSG DrugBank: DB00675
Description	METTL14 deficiency inbeta-cells induces glucose intolerance and a decrease in insulin secretion.To define the role of m6A in regulating the beta-cell function, the study generated beta-cell METTL14-specific knockout (beta-KO) mice by tamoxifen administration. beta-cell mass in beta-KO mice was related to beta-cell proliferation and also observed elevated mRNA and protein levels of Ire1-alpha and sXBP-1 in beta-KO islets.	[192]
Compound Name	N~2~-hexyl-6,7-dimethoxy-N~4~-(1-methylpiperidin-4-yl)quinazoline-2,4-diamine	Investigative
Synonyms	CHEMBL4086403; SCHEMBL23260478; MS012; BDBM50501525; MS 012; MS-012; N~2~-hexyl-6,7-dimethoxy-N~4~-(1-methylpiperidin-4-yl)quinazoline-2,4-diamine; 2089617-83-2 Click to Show/Hide
External link	CID: 137348638
Activity	IC50=7±2 nM	[199]
Compound Name	6,7-Dimethoxy-N-(1-Methylpiperidin-4-Yl)-2-(Morpholin-4-Yl)quinazolin-4-Amine	Investigative
Synonyms	CHEMBL571717; 6,7-Dimethoxy-N-(1-Methylpiperidin-4-Yl)-2-(Morpholin-4-Yl)quinazolin-4-Amine; 7L6; SCHEMBL15280520; BDBM50300032; NCGC00185861-01; 6,7-dimethoxy-N-(1-methylpiperidin-4-yl)-2-morpholinoquinazolin-4-amine Click to Show/Hide
External link	CID: 44605026
Activity	IC50=13 ± 4 nM	[199]

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m6A Regulator Information

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Prof. Feng ZHU

Prof. Shuiping Liu

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