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.

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.

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.

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.

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.

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

Cytomegaloviral disease [ICD-11: 1DB2]

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]
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.Z]
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.

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.

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).

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

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

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[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	()
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.

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.

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				[62]
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.

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				[63]
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.

Mammalian target of rapamycin complex 2 (mTORC2)

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				[64]
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.

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				[65]
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.

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		[66]
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				[67]
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				[68]
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.

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.

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		[69]
Responsed Disease	Atherosclerosis [ICD-11: BD40.Z]

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.

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				[70]
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.

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				[71]
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				[72]
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				[73]
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				[74]
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				[75]
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

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				[76]
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		[69]
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				[77]
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				[78]
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.

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).

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				[79]
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		[80]
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-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				[81]
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				[82]
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

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

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[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

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				[83]
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 (circNOTCH1)

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				[84]
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.

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				[85]
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.

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				[63]
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.

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				[87]
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		[88]
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				[89]
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				[90]
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		[91]
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.

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				[92]
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				[93]
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				[94]
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		[95]
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				[96]
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		[97]
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		[98]
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				[99]
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				[100]
Responsed Disease	Glucose Intolerance [ICD-11: 5C61.Y]
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.

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		[101]
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		[102]
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			[103]
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				[104]
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				[105]
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.

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.

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.

Mammalian target of rapamycin complex 2 (mTORC2)

Target Gene

Gemcitabine [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[64]
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.

hsa_circ_0008399

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				[83]
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.

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		[86]
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.

Sunitinib [Approved]

In total 1 item(s) under this drug			Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene			[103]
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				[104]
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

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.	[100]
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	[106]
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	[106]

References

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Ref 4	LNC942 promoting METTL14-mediated m(6)A methylation in breast cancer cell proliferation and progression. Oncogene. 2020 Jul;39(31):5358-5372. doi: 10.1038/s41388-020-1338-9. Epub 2020 Jun 23.
Ref 5	m(6) A RNA methyltransferases METTL3/14 regulate immune responses to anti-PD-1 therapy. EMBO J. 2020 Oct 15;39(20):e104514. doi: 10.15252/embj.2020104514. Epub 2020 Sep 23.
Ref 6	m(6)A mRNA methylation regulates testosterone synthesis through modulating autophagy in Leydig cells. Autophagy. 2021 Feb;17(2):457-475. doi: 10.1080/15548627.2020.1720431. Epub 2020 Jan 31.
Ref 7	METTL14 Overexpression Promotes Osteosarcoma Cell Apoptosis and Slows Tumor Progression via Caspase 3 Activation. Cancer Manag Res. 2020 Dec 11;12:12759-12767. doi: 10.2147/CMAR.S284273. eCollection 2020.
Ref 8	N6-methyladenosine regulated FGFR4 attenuates ferroptotic cell death in recalcitrant HER2-positive breast cancer. Nat Commun. 2022 May 13;13(1):2672. doi: 10.1038/s41467-022-30217-7.
Ref 9	Mettl14 Attenuates Cardiac Ischemia/Reperfusion Injury by Regulating Wnt1/Beta-Catenin Signaling Pathway. Front Cell Dev Biol. 2021 Dec 16;9:762853. doi: 10.3389/fcell.2021.762853. eCollection 2021.
Ref 10	The m(6)A RNA methyltransferase METTL3/METTL14 promotes leukemogenesis through the mdm2/p53 pathway in acute myeloid leukemia. J Cancer. 2022 Jan 4;13(3):1019-1030. doi: 10.7150/jca.60381. eCollection 2022.
Ref 11	Hypoxia blocks ferroptosis of hepatocellular carcinoma via suppression of METTL14 triggered YTHDF2-dependent silencing of SLC7A11. J Cell Mol Med. 2021 Nov;25(21):10197-10212. doi: 10.1111/jcmm.16957. Epub 2021 Oct 5.
Ref 12	Mettl14-mediated m6A modification modulates neuron apoptosis during the repair of spinal cord injury by regulating the transformation from pri-mir-375 to miR-375. Cell Biosci. 2021 Mar 11;11(1):52. doi: 10.1186/s13578-020-00526-9.
Ref 13	METTL14 facilitates global genome repair and suppresses skin tumorigenesis. Proc Natl Acad Sci U S A. 2021 Aug 31;118(35):e2025948118. doi: 10.1073/pnas.2025948118.
Ref 14	HRD1-mediated METTL14 degradation regulates m(6)A mRNA modification to suppress ER proteotoxic liver disease. Mol Cell. 2021 Dec 16;81(24):5052-5065.e6. doi: 10.1016/j.molcel.2021.10.028. Epub 2021 Nov 29.
Ref 15	N6-Methyladenosine modification of the TRIM7 positively regulates tumorigenesis and chemoresistance in osteosarcoma through ubiquitination of BRMS1. EBioMedicine. 2020 Sep;59:102955. doi: 10.1016/j.ebiom.2020.102955. Epub 2020 Aug 24.
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Ref 18	TNF-Alpha-mediated m(6)A modification of ELMO1 triggers directional migration of mesenchymal stem cell in ankylosing spondylitis. Nat Commun. 2021 Sep 10;12(1):5373. doi: 10.1038/s41467-021-25710-4.
Ref 19	Dynamic m(6)A mRNA Methylation Reveals the Role of METTL3/14-m(6)A-MNK2-ERK Signaling Axis in Skeletal Muscle Differentiation and Regeneration. Front Cell Dev Biol. 2021 Oct 1;9:744171. doi: 10.3389/fcell.2021.744171. eCollection 2021.
Ref 20	METTL14 Inhibits Hepatocellular Carcinoma Metastasis Through Regulating EGFR/PI3K/AKT Signaling Pathway in an m6A-Dependent Manner. Cancer Manag Res. 2020 Dec 23;12:13173-13184. doi: 10.2147/CMAR.S286275. eCollection 2020.
Ref 21	N6-Methyladenosine Methyltransferase METTL14-Mediated Autophagy in Malignant Development of Oral Squamous Cell Carcinoma. Front Oncol. 2021 Nov 24;11:738406. doi: 10.3389/fonc.2021.738406. eCollection 2021.
Ref 22	METTL14 aggravates endothelial inflammation and atherosclerosis by increasing FOXO1 N6-methyladeosine modifications. Theranostics. 2020 Jul 11;10(20):8939-8956. doi: 10.7150/thno.45178. eCollection 2020.
Ref 23	Upregulation of METTL14 contributes to trophoblast dysfunction by elevating FOXO3a expression in an m(6)A-dependent manner. Placenta. 2022 Jun 24;124:18-27. doi: 10.1016/j.placenta.2022.05.008. Epub 2022 May 14.
Ref 24	Integrated analysis of the transcriptome-wide m6A methylome in preeclampsia and healthy control placentas. PeerJ. 2020 Sep 15;8:e9880. doi: 10.7717/peerj.9880. eCollection 2020.
Ref 25	m6A RNA methylation-mediated HNF3Gamma reduction renders hepatocellular carcinoma dedifferentiation and sorafenib resistance. Signal Transduct Target Ther. 2020 Dec 26;5(1):296. doi: 10.1038/s41392-020-00299-0.
Ref 26	Cap-independent mRNA translation is upregulated in long-lived endocrine mutant mice. J Mol Endocrinol. 2019 Aug 1;63(2):123-138. doi: 10.1530/JME-19-0021.
Ref 27	METTL14-mediated N(6)-methyladenosine modification of ITGB4 mRNA inhibits metastasis of clear cell renal cell carcinoma. Cell Commun Signal. 2022 Mar 19;20(1):36. doi: 10.1186/s12964-022-00831-5.
Ref 28	RNA m(6) A modification enzymes shape innate responses to DNA by regulating interferon Beta. Genes Dev. 2018 Dec 1;32(23-24):1472-1484. doi: 10.1101/gad.319475.118. Epub 2018 Nov 21.
Ref 29	Mettl14 mediates the inflammatory response of macrophages in atherosclerosis through the NF-KappaB/IL-6 signaling pathway. Cell Mol Life Sci. 2022 May 22;79(6):311. doi: 10.1007/s00018-022-04331-0.
Ref 30	Methyl CpG binding protein 2 promotes colorectal cancer metastasis by regulating N(6) -methyladenosine methylation through methyltransferase-like 14. Cancer Sci. 2021 Aug;112(8):3243-3254. doi: 10.1111/cas.15011. Epub 2021 Jun 29.
Ref 31	m(6)A RNA Methylation Regulates the Self-Renewal and Tumorigenesis of Glioblastoma Stem Cells. Cell Rep. 2017 Mar 14;18(11):2622-2634. doi: 10.1016/j.celrep.2017.02.059.
Ref 32	Methyltransferase-like (METTL)14-mediated N6-methyladenosine modification modulates retinal pigment epithelial (RPE) activity by regulating the methylation of microtubule-associated protein (MAP)2. Bioengineered. 2022 Mar;13(3):4773-4785. doi: 10.1080/21655979.2022.2032968.
Ref 33	The m6A Methyltransferase METTL14-Mediated N6-Methyladenosine Modification of PTEN mRNA Inhibits Tumor Growth and Metastasis in Stomach Adenocarcinoma. Front Oncol. 2021 Aug 12;11:699749. doi: 10.3389/fonc.2021.699749. eCollection 2021.
Ref 34	METTL14-mediated N6-methyladenosine modification of Pten mRNA inhibits tumour progression in clear-cell renal cell carcinoma. Br J Cancer. 2022 Jul;127(1):30-42. doi: 10.1038/s41416-022-01757-y. Epub 2022 Mar 5.
Ref 35	METTL14-regulated PI3K/Akt signaling pathway via PTEN affects HDAC5-mediated epithelial-mesenchymal transition of renal tubular cells in diabetic kidney disease. Cell Death Dis. 2021 Jan 4;12(1):32. doi: 10.1038/s41419-020-03312-0.
Ref 36	METTL14 Inhibits Hematopoietic Stem/Progenitor Differentiation and Promotes Leukemogenesis via mRNA m(6)A Modification. Cell Stem Cell. 2018 Feb 1;22(2):191-205.e9. doi: 10.1016/j.stem.2017.11.016. Epub 2017 Dec 28.
Ref 37	METTL14 aggravates podocyte injury and glomerulopathy progression through N(6)-methyladenosine-dependent downregulating of Sirt1. Cell Death Dis. 2021 Sep 27;12(10):881. doi: 10.1038/s41419-021-04156-y.
Ref 38	Mettl14 inhibits bladder TIC self-renewal and bladder tumorigenesis through N(6)-methyladenosine of Notch1. Mol Cancer. 2019 Nov 25;18(1):168. doi: 10.1186/s12943-019-1084-1.
Ref 39	m(6)A mRNA modification maintains colonic epithelial cell homeostasis via NF-KappaB-mediated antiapoptotic pathway. Sci Adv. 2022 Mar 25;8(12):eabl5723. doi: 10.1126/sciadv.abl5723. Epub 2022 Mar 25.
Ref 40	Downregulated METTL14 accumulates BPTF that reinforces super-enhancers and distal lung metastasis via glycolytic reprogramming in renal cell carcinoma. Theranostics. 2021 Jan 26;11(8):3676-3693. doi: 10.7150/thno.55424. eCollection 2021.
Ref 41	Upregulation of METTL14 mediates the elevation of PERP mRNA N(6) adenosine methylation promoting the growth and metastasis of pancreatic cancer. Mol Cancer. 2020 Aug 25;19(1):130. doi: 10.1186/s12943-020-01249-8.
Ref 42	m(6)A mRNA methylation regulates AKT activity to promote the proliferation and tumorigenicity of endometrial cancer. Nat Cell Biol. 2018 Sep;20(9):1074-1083. doi: 10.1038/s41556-018-0174-4. Epub 2018 Aug 27.
Ref 43	The m6A methyltransferase METTL14 inhibits the proliferation, migration, and invasion of gastric cancer by regulating the PI3K/AKT/mTOR signaling pathway. J Clin Lab Anal. 2021 Mar;35(3):e23655. doi: 10.1002/jcla.23655. Epub 2020 Dec 12.
Ref 44	N(6)-methyladenosine mRNA methylation of PIK3CB regulates AKT signalling to promote PTEN-deficient pancreatic cancer progression. Gut. 2020 Dec;69(12):2180-2192. doi: 10.1136/gutjnl-2019-320179. Epub 2020 Apr 20.
Ref 45	METTL14-mediated m(6)A modification of circORC5 suppresses gastric cancer progression by regulating miR-30c-2-3p/AKT1S1 axis. Mol Cancer. 2022 Feb 14;21(1):51. doi: 10.1186/s12943-022-01521-z.
Ref 46	Comprehensive Analyses Identify APOBEC3A as a Genomic Instability-Associated Immune Prognostic Biomarker in Ovarian Cancer. Front Immunol. 2021 Oct 21;12:749369. doi: 10.3389/fimmu.2021.749369. eCollection 2021.
Ref 47	N (6)-Methyladenosine modification of hepatitis B and C viral RNAs attenuates host innate immunity via RIG-I signaling. J Biol Chem. 2020 Sep 11;295(37):13123-13133. doi: 10.1074/jbc.RA120.014260. Epub 2020 Jul 27.
Ref 48	Downregulation of Methyltransferase-Like 14 Promotes Ovarian Cancer Cell Proliferation Through Stabilizing TROAP mRNA. Front Oncol. 2022 Feb 18;12:824258. doi: 10.3389/fonc.2022.824258. eCollection 2022.
Ref 49	METTL14 promotes prostate tumorigenesis by inhibiting THBS1 via an m6A-YTHDF2-dependent mechanism. Cell Death Discov. 2022 Mar 30;8(1):143. doi: 10.1038/s41420-022-00939-0.
Ref 50	N(6)-methyladenosine-modified TRAF1 promotes sunitinib resistance by regulating apoptosis and angiogenesis in a METTL14-dependent manner in renal cell carcinoma. Mol Cancer. 2022 May 10;21(1):111. doi: 10.1186/s12943-022-01549-1.
Ref 51	YTHDF1 promotes breast cancer cell growth, DNA damage repair and chemoresistance. Cell Death Dis. 2022 Mar 12;13(3):230. doi: 10.1038/s41419-022-04672-5.
Ref 52	METTL14-mediated N6-methyladenosine modification of SOX4 mRNA inhibits tumor metastasis in colorectal cancer. Mol Cancer. 2020 Jun 17;19(1):106. doi: 10.1186/s12943-020-01220-7.
Ref 53	The N6-methyladenosine mRNA methylase METTL14 promotes renal ischemic reperfusion injury via suppressing YAP1. J Cell Biochem. 2020 Jan;121(1):524-533. doi: 10.1002/jcb.29258. Epub 2019 Jul 18.
Ref 54	A methyltransferase-like 14/miR-99a-5p/tribble 2 positive feedback circuit promotes cancer stem cell persistence and radioresistance via histone deacetylase 2-mediated epigenetic modulation in esophageal squamous cell carcinoma. Clin Transl Med. 2021 Sep;11(9):e545. doi: 10.1002/ctm2.545.
Ref 55	METTL14 promotes glomerular endothelial cell injury and diabetic nephropathy via m6A modification of Alpha-klotho. Mol Med. 2021 Sep 9;27(1):106. doi: 10.1186/s10020-021-00365-5.
Ref 56	MiR-4729 regulates TIE1 mRNA m6A modification and angiogenesis in hemorrhoids by targeting METTL14. Ann Transl Med. 2021 Feb;9(3):232. doi: 10.21037/atm-20-3399.
Ref 57	METTL14 benefits the mesenchymal stem cells in patients with steroid-associated osteonecrosis of the femoral head by regulating the m6A level of PTPN6. Aging (Albany NY). 2021 Dec 15;13(24):25903-25919. doi: 10.18632/aging.203778. Epub 2021 Dec 15.
Ref 58	USP48 Is Upregulated by Mettl14 to Attenuate Hepatocellular Carcinoma via Regulating SIRT6 Stabilization. Cancer Res. 2021 Jul 15;81(14):3822-3834. doi: 10.1158/0008-5472.CAN-20-4163. Epub 2021 Apr 26.
Ref 59	LncRNA HCG11 mediated by METTL14 inhibits the growth of lung adenocarcinoma via IGF2BP2/LATS1. Biochem Biophys Res Commun. 2021 Nov 26;580:74-80. doi: 10.1016/j.bbrc.2021.09.083. Epub 2021 Oct 2.
Ref 60	Methyltransferase-like 14 suppresses growth and metastasis of renal cell carcinoma by decreasing long noncoding RNA NEAT1. Cancer Sci. 2022 Feb;113(2):446-458. doi: 10.1111/cas.15212. Epub 2021 Dec 16.
Ref 61	DARS-AS1 recruits METTL3/METTL14 to bind and enhance DARS mRNA m(6)A modification and translation for cytoprotective autophagy in cervical cancer. RNA Biol. 2022 Jan;19(1):751-763. doi: 10.1080/15476286.2022.2079889.
Ref 62	Methylation of adenosine at the N(6) position post-transcriptionally regulates hepatic P450s expression. Biochem Pharmacol. 2020 Jan;171:113697. doi: 10.1016/j.bcp.2019.113697. Epub 2019 Nov 7.
Ref 63	METTL14-mediated Lnc-LSG1 m6A modification inhibits clear cell renal cell carcinoma metastasis via regulating ESRP2 ubiquitination. Mol Ther Nucleic Acids. 2021 Dec 17;27:547-561. doi: 10.1016/j.omtn.2021.12.024. eCollection 2022 Mar 8.
Ref 64	m(6)A Methyltransferase METTL14-Mediated Upregulation of Cytidine Deaminase Promoting Gemcitabine Resistance in Pancreatic Cancer. Front Oncol. 2021 Aug 11;11:696371. doi: 10.3389/fonc.2021.696371. eCollection 2021.
Ref 65	METTL14 suppresses the metastatic potential of hepatocellular carcinoma by modulating N(6) -methyladenosine-dependent primary MicroRNA processing. Hepatology. 2017 Feb;65(2):529-543. doi: 10.1002/hep.28885. Epub 2016 Dec 24.
Ref 66	METTL3/METTL14 Transactivation and m(6)A-Dependent TGF-Beta1 Translation in Activated Kupffer Cells. Cell Mol Gastroenterol Hepatol. 2021;12(3):839-856. doi: 10.1016/j.jcmgh.2021.05.007. Epub 2021 May 13.
Ref 67	The m(6)A-suppressed P2RX6 activation promotes renal cancer cells migration and invasion through ATP-induced Ca(2+) influx modulating ERK1/2 phosphorylation and MMP9 signaling pathway. J Exp Clin Cancer Res. 2019 Jun 3;38(1):233. doi: 10.1186/s13046-019-1223-y.
Ref 68	New insight into the catalytic -dependent and -independent roles of METTL3 in sustaining aberrant translation in chronic myeloid leukemia. Cell Death Dis. 2021 Sep 24;12(10):870. doi: 10.1038/s41419-021-04169-7.
Ref 69	METTL14 mediated m6A modification to LncRNA ZFAS1/ RAB22A: A novel therapeutic target for atherosclerosis. Int J Cardiol. 2021 Apr 1;328:177. doi: 10.1016/j.ijcard.2020.12.002. Epub 2020 Dec 8.
Ref 70	METTL14 suppresses pyroptosis and diabetic cardiomyopathy by downregulating TINCR lncRNA. Cell Death Dis. 2022 Jan 10;13(1):38. doi: 10.1038/s41419-021-04484-z.
Ref 71	N6-methyladenosine methyltransferase plays a role in hypoxic preconditioning partially through the interaction with lncRNA H19. Acta Biochim Biophys Sin (Shanghai). 2020 Dec 29;52(12):1306-1315. doi: 10.1093/abbs/gmaa130.
Ref 72	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. Mol Oncol. 2020 Jun;14(6):1282-1296. doi: 10.1002/1878-0261.12676. Epub 2020 Apr 13.
Ref 73	N6-methyladenosine (m6A)-mediated up-regulation of long noncoding RNA LINC01320 promotes the proliferation, migration, and invasion of gastric cancer via miR495-5p/RAB19 axis. Bioengineered. 2021 Dec;12(1):4081-4091. doi: 10.1080/21655979.2021.1953210.
Ref 74	Nuclear export of chimeric mRNAs depends on an lncRNA-triggered autoregulatory loop in blood malignancies. Cell Death Dis. 2020 Jul 23;11(7):566. doi: 10.1038/s41419-020-02795-1.
Ref 75	Mechanism of METTL14 and m6A modification of lncRNA MALAT1 in the proliferation of oral squamous cell carcinoma cells. Oral Dis. 2022 Apr 25. doi: 10.1111/odi.14220. Online ahead of print.
Ref 76	METTL14 suppresses proliferation and metastasis of colorectal cancer by down-regulating oncogenic long non-coding RNA XIST. Mol Cancer. 2020 Feb 28;19(1):46. doi: 10.1186/s12943-020-1146-4.
Ref 77	MicroRNA-211 attenuates cell proliferation in T-cell lymphoblastic lymphoma through targeting TCF12. Leuk Res. 2021 Nov;110:106653. doi: 10.1016/j.leukres.2021.106653. Epub 2021 Jun 29.
Ref 78	RETRACTED: METTL14 Suppresses CRC Progression via Regulating N6-Methyladenosine-Dependent Primary miR-375 Processing. Mol Ther. 2020 Feb 5;28(2):599-612. doi: 10.1016/j.ymthe.2019.11.016. Epub 2019 Nov 20.
Ref 79	METTL14 promotes the migration and invasion of breast cancer cells by modulating N6?methyladenosine and hsa?miR?146a?5p expression. Oncol Rep. 2020 May;43(5):1375-1386. doi: 10.3892/or.2020.7515. Epub 2020 Feb 24.
Ref 80	METTL14 regulates M6A methylation-modified primary miR-19a to promote cardiovascular endothelial cell proliferation and invasion. Eur Rev Med Pharmacol Sci. 2020 Jun;24(12):7015-7023. doi: 10.26355/eurrev_202006_21694.
Ref 81	METTL14-Mediated miR-30c-1-3p Maturation Represses the Progression of Lung Cancer via Regulation of MARCKSL1 Expression. Mol Biotechnol. 2022 Feb;64(2):199-212. doi: 10.1007/s12033-021-00406-8. Epub 2021 Sep 29.
Ref 82	N(6)-methyladenosine-mediated miR-380-3p maturation and upregulation promotes cancer aggressiveness in pancreatic cancer. Bioengineered. 2022 Jun;13(6):14460-14471. doi: 10.1080/21655979.2022.2088497.
Ref 83	Circ0008399 Interaction with WTAP Promotes Assembly and Activity of the m(6)A Methyltransferase Complex and Promotes Cisplatin Resistance in Bladder Cancer. Cancer Res. 2021 Dec 15;81(24):6142-6156. doi: 10.1158/0008-5472.CAN-21-1518. Epub 2021 Oct 26.
Ref 84	G protein-coupled oestrogen receptor promotes cell growth of non-small cell lung cancer cells via YAP1/QKI/circNOTCH1/m6A methylated NOTCH1 signalling. J Cell Mol Med. 2021 Jan;25(1):284-296. doi: 10.1111/jcmm.15997. Epub 2020 Nov 25.
Ref 85	Novel circGFRAlpha1 Promotes Self-Renewal of Female Germline Stem Cells Mediated by m(6)A Writer METTL14. Front Cell Dev Biol. 2021 Apr 12;9:640402. doi: 10.3389/fcell.2021.640402. eCollection 2021.
Ref 86	N(6)-methyladenosine mediates the cellular proliferation and apoptosis via microRNAs in arsenite-transformed cells. Toxicol Lett. 2018 Aug;292:1-11. doi: 10.1016/j.toxlet.2018.04.018. Epub 2018 Apr 20.
Ref 87	N(6) -Methyladenosine Negatively Regulates Human Respiratory Syncytial Virus Replication. Front Cell Dev Biol. 2021 Oct 4;9:739445. doi: 10.3389/fcell.2021.739445. eCollection 2021.
Ref 88	METTL14 Gene Polymorphisms Confer Neuroblastoma Susceptibility: An Eight-Center Case-Control Study. Mol Ther Nucleic Acids. 2020 Aug 14;22:17-26. doi: 10.1016/j.omtn.2020.08.009. Online ahead of print.
Ref 89	Integrated analysis of transcriptome-wide m(6)A methylome of osteosarcoma stem cells enriched by chemotherapy. Epigenomics. 2019 Nov 1;11(15):1693-1715. doi: 10.2217/epi-2019-0262. Epub 2019 Oct 25.
Ref 90	Overexpression of methyltransferase-like 3 and 14 in oral squamous cell carcinoma. J Oral Pathol Med. 2022 Feb;51(2):134-145. doi: 10.1111/jop.13256. Epub 2021 Nov 3.
Ref 91	Prognostic Implication of the m(6)A RNA Methylation Regulators in Rectal Cancer. Front Genet. 2021 Jun 3;12:604229. doi: 10.3389/fgene.2021.604229. eCollection 2021.
Ref 92	Knockdown of METTL14 suppresses the malignant progression of non-small cell lung cancer by reducing Twist expression. Oncol Lett. 2021 Dec;22(6):847. doi: 10.3892/ol.2021.13108. Epub 2021 Oct 21.
Ref 93	METTL3 regulates m6A in endometrioid epithelial ovarian cancer independently of METTl14 and WTAP. Cell Biol Int. 2020 Dec;44(12):2524-2531. doi: 10.1002/cbin.11459. Epub 2020 Sep 11.
Ref 94	Knockdown of METTL14 inhibits the growth and invasion of cervical cancer. Transl Cancer Res. 2019 Oct;8(6):2307-2315. doi: 10.21037/tcr.2019.09.48.
Ref 95	Gene signatures and prognostic values of m6A regulators in clear cell renal cell carcinoma - a retrospective study using TCGA database. Aging (Albany NY). 2019 Mar 15;11(6):1633-1647. doi: 10.18632/aging.101856.
Ref 96	Downregulation of m(6) A writer complex member METTL14 in bladder urothelial carcinoma suppresses tumor aggressiveness. Mol Oncol. 2022 May;16(9):1841-1856. doi: 10.1002/1878-0261.13181. Epub 2022 Mar 24.
Ref 97	RNA N (6)-Methyladenosine Modification in Normal and Malignant Hematopoiesis. Adv Exp Med Biol. 2019;1143:75-93. doi: 10.1007/978-981-13-7342-8_4.
Ref 98	The study of METTL14, ALKBH5, and YTHDF2 in peripheral blood mononuclear cells from systemic lupus erythematosus. Mol Genet Genomic Med. 2020 Sep;8(9):e1298. doi: 10.1002/mgg3.1298. Epub 2020 Jun 25.
Ref 99	The RNA Methyltransferase Complex of WTAP, METTL3, and METTL14 Regulates Mitotic Clonal Expansion in Adipogenesis. Mol Cell Biol. 2018 Jul 30;38(16):e00116-18. doi: 10.1128/MCB.00116-18. Print 2018 Aug 15.
Ref 100	Acute Deletion of METTL14 in Beta-Cells of Adult Mice Results in Glucose Intolerance. Endocrinology. 2019 Oct 1;160(10):2388-2394. doi: 10.1210/en.2019-00350.
Ref 101	Increased m6A methylation level is associated with the progression of human abdominal aortic aneurysm. Ann Transl Med. 2019 Dec;7(24):797. doi: 10.21037/atm.2019.12.65.
Ref 102	METTL14-dependent m6A regulates vascular calcification induced by indoxyl sulfate. Life Sci. 2019 Dec 15;239:117034. doi: 10.1016/j.lfs.2019.117034. Epub 2019 Nov 4.
Ref 103	Alteration of N(6)-Methyladenosine mRNA Methylation in a Human Stem Cell-Derived Cardiomyocyte Model of Tyrosine Kinase Inhibitor-Induced Cardiotoxicity. Front Cardiovasc Med. 2022 Mar 23;9:849175. doi: 10.3389/fcvm.2022.849175. eCollection 2022.
Ref 104	Meclofenamic acid represses spermatogonial proliferation through modulating m(6)A RNA modification. J Anim Sci Biotechnol. 2019 Jul 11;10:63. doi: 10.1186/s40104-019-0361-6. eCollection 2019.
Ref 105	Mettl3-/Mettl14-mediated mRNA N(6)-methyladenosine modulates murine spermatogenesis. Cell Res. 2017 Oct;27(10):1216-1230. doi: 10.1038/cr.2017.117. Epub 2017 Sep 15.
Ref 106	Discovery of Potent and Selective Inhibitors for G9a-Like Protein (GLP) Lysine Methyltransferase. J Med Chem. 2017 Mar 9;60(5):1876-1891. doi: 10.1021/acs.jmedchem.6b01645. Epub 2017 Feb 14.

m6A Regulator Information

Cite M6AREG

Correspondence

Prof. Feng ZHU

Prof. Shuiping Liu

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