m6A Regulator Information

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

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
	C2C12	Normal	Mus musculus	CVCL_0188