m6A Target Gene Information

General Information of the m6A Target Gene (ID: M6ATAR00375)

Target Name	Mutated in multiple advanced cancers 1 (PTEN)
Synonyms	Mutated in multiple advanced cancers 1; Phosphatase and tensin homolog; MMAC1; TEP1 Click to Show/Hide
Gene Name	PTEN
Chromosomal Location	10q23.31
Family	PTEN phosphatase protein family
Function	Tumor suppressor. Acts as a dual-specificity protein phosphatase, dephosphorylating tyrosine-, serine- and threonine-phosphorylated proteins. Also acts as a lipid phosphatase, removing the phosphate in the D3 position of the inositol ring from phosphatidylinositol 3,4,5-trisphosphate, phosphatidylinositol 3,4-diphosphate, phosphatidylinositol 3-phosphate and inositol 1,3,4,5-tetrakisphosphate with order of substrate preference in vitro PtdIns(3,4,5)P3 > PtdIns(3,4)P2 > PtdIns3P > Ins(1,3,4,5)P4. The lipid phosphatase activity is critical for its tumor suppressor function. Antagonizes the PI3K-AKT/PKB signaling pathway by dephosphorylating phosphoinositides and thereby modulating cell cycle progression and cell survival. The unphosphorylated form cooperates with MAGI2 to suppress AKT1 activation. Dephosphorylates tyrosine-phosphorylated focal adhesion kinase and inhibits cell migration and integrin-mediated cell spreading and focal adhesion formation. Plays a role as a key modulator of the AKT-mTOR signaling pathway controlling the tempo of the process of newborn neurons integration during adult neurogenesis, including correct neuron positioning, dendritic development and synapse formation. May be a negative regulator of insulin signaling and glucose metabolism in adipose tissue. The nuclear monoubiquitinated form possesses greater apoptotic potential, whereas the cytoplasmic nonubiquitinated form induces less tumor suppressive ability. In motile cells, suppresses the formation of lateral pseudopods and thereby promotes cell polarization and directed movement.; [Isoform alpha]: Functional kinase, like isoform 1 it antagonizes the PI3K-AKT/PKB signaling pathway. Plays a role in mitochondrial energetic metabolism by promoting COX activity and ATP production, via collaboration with isoform 1 in increasing protein levels of PINK1. Click to Show/Hide
Gene ID	5728
Uniprot ID	PTEN_HUMAN
HGNC ID	HGNC:9588
Ensembl Gene ID	ENSG00000171862
KEGG ID	hsa:5728

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

PTEN can be regulated by the following regulator(s), and cause disease/drug response(s). You can browse detail information of regulator(s) or disease/drug response(s).

Browse Regulator

Browse Disease

Methyltransferase-like 3 (METTL3) [WRITER]

Regulator Info

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	LX2 cell line	Homo sapiens
Treatment: shMETTL3 LX2 cells Control: shLuc LX2 cells		GSE207909
Regulation		logFC: 9.60E-01 p-value: 1.46E-37
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between PTEN and the regulator*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 2.25E+00	GSE60213

In total 4 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene				[1]
Response Summary	METTL3 depletion in human myeloid leukemia cell lines induces cell differentiation and apoptosis and delays leukemia progression in recipient mice in vivo. Single-nucleotide-resolution mapping of m6A coupled with ribosome profiling reveals that m6A promotes the translation of c-MYC, BCL2 and Mutated in multiple advanced cancers 1 (PTEN) mRNAs in the human acute myeloid leukemia MOLM-13 cell line. Moreover, loss of METTL3 leads to increased levels of phosphorylated AKT.
Target Regulation	Up regulation
Responsed Disease	Acute myeloid leukaemia		ICD-11: 2A60	Disease Info
Cell Process	Cell differentiation and apoptosis
	Apoptosis (hsa04210)
In-vitro Model	HSPC (Human hematopoietic stem cell)
In-vivo Model	500,000 selected cells were injected via tail vein or retro-orbital route into female NSG (6-8 week old) recipient mice that had been sublethally irradiated with 475 cGy one day before transplantation.
Experiment 2 Reporting the m6A Methylation Regulator of This Target Gene				[2]
Response Summary	The molecular mechanism underlying the effect of LINC00470 on chronic myelocytic leukaemia by reducing the Mutated in multiple advanced cancers 1 (PTEN) stability via RNA methyltransferase METTL3, thus leading to the inhibition of cell autophagy while promoting chemoresistance in CML.
Target Regulation	Down regulation
Responsed Disease	Chronic myeloid leukaemia		ICD-11: 2B33.2	Disease Info
Pathway Response	Autophagy			hsa04140
Cell Process	RNA stability
	Cell autophagy
In-vitro Model	K-562	Chronic myelogenous leukemia	Homo sapiens	CVCL_0004
	KCL-22	Chronic myelogenous leukemia	Homo sapiens	CVCL_2091
In-vivo Model	In the control mice or ADR mice group, the parental or chemo-resistant K562 cells were infected with LV-shCtrl. In the ADR + shLINC00470 group, the chemo-resistant K562 cells were infected with LV- shLINC00470. These cells were injected, respectively, into these 5-week-old mice subcutaneously.
Experiment 3 Reporting the m6A Methylation Regulator of This Target Gene				[3]
Response Summary	Bete-elemene exerted the restrictive impacts on the cell growth of lung cancer in vivo and in vitro through targeting METTL3. Bete-elemene contributed to the augmented PTEN expression via suppressing its m6A modification.
Target Regulation	Down regulation
Responsed Disease	Lung cancer		ICD-11: 2C25	Disease Info
In-vitro Model	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
In-vivo Model	Four-week-old BALB/c nude mice were randomly divided into three groups: (1) vector group, (2) vector + Bete-elemene group, and (3) Bete-elemene + METTL3 group. Nude mice were raised in an SPF level animal house and were free to eat and drink. Mice in the vector group were subcutaneously injected with lung cancer cells transfected with empty vector and did not receive Bete-elemene administration, and this group was implemented as the negative control. Following establishing orthotopic xenografts by using A549 or H1299 cells transfected with empty vector, mice in the vector + Bete-elemene group underwent intraperitoneal injection with Bete-elemene once a day. For the subcutaneous transplanted model, A549 or H1299 cells transfected with METTL3-overexpressing vector were inoculated into mice from the Bete-elemene + METTL3 group. Then, mice were intraperitoneally administrated with Bete-elemene once a day. Three weeks later, all the animals were euthanized with CO2. Xenografts were removed and weighted after mice were euthanatized.
Experiment 4 Reporting the m6A Methylation Regulator of This Target Gene				[4]
Response Summary	METTL3/YTHDF2/Mutated in multiple advanced cancers 1 (PTEN) axis exerts a significant role in hypoxia induced PASMCs proliferation, providing a novel therapeutic target for hypoxic pulmonary hypertension.
Target Regulation	Down regulation
Responsed Disease	Pulmonary hypertension due to lung disease or hypoxia		ICD-11: BB01.2	Disease Info
Pathway Response	PI3K-Akt signaling pathway			hsa04151
Cell Process	Cell apoptosis
In-vitro Model	PASMC cell line (Pulmonary artery smooth muscle cell)
In-vivo Model	10 rats were divided into control and HPH group. In detail, 5 rats of the hypoxia groups were exposed to hypoxia (10%O₂) chamber (AiPu XBS-02B, China) for 4 weeks. In addition, 5 rats of control group were kept under normoxic conditions (21% O₂) for 4 weeks. Rats were housed in standard polypropylene cages under controlled photocycle (12 h light/12 h dark) under 22-25 ℃ temperature.

Methyltransferase-like 14 (METTL14) [WRITER]

Regulator Info

*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

In total 3 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene				[5]
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.
Target Regulation	Up regulation
Responsed Disease	Gastric cancer		ICD-11: 2B72.Z	Disease Info
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.
Experiment 2 Reporting the m6A Methylation Regulator of This Target Gene				[6]
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.
Target Regulation	Up regulation
Responsed Disease	Renal cell carcinoma of kidney		ICD-11: 2C90.0	Disease Info
Pathway Response	PI3K-Akt signaling pathway			hsa04151
Experiment 3 Reporting the m6A Methylation Regulator of This Target Gene				[7]
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.
Target Regulation	Down regulation
Responsed Disease	Chronic kidney disease		ICD-11: GB61.Z	Disease Info
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).

RNA demethylase ALKBH5 (ALKBH5) [ERASER]

Regulator Info

*Representative RNA-seq result indicating the expression of this target gene regulated by ALKBH5*
Cell Line	MOLM-13 cell line	Homo sapiens
Treatment: shALKBH5 MOLM-13 cells Control: shNS MOLM-13 cells		GSE144968
Regulation		logFC: -2.10E+00 p-value: 1.89E-02
More Results	Click to View More RNA-seq Results

In total 1 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene				[8]
Response Summary	ALKBH5-mediated m6A demethylation enhanced the stability of KCNK15-AS1. In pancreatic cancer, KCNK15-AS1 bound to KCNK15 to inhibit its translation, and interacted with MDM2 to induce REST ubiquitination, which eventually facilitated Mutated in multiple advanced cancers 1 (PTEN) transcription to inactivate AKT pathway.
Responsed Disease	Pancreatic cancer		ICD-11: 2C10	Disease Info
Pathway Response	.PI3K-Akt signaling pathway			hsa04151
Cell Process	Cell proliferation
	Cell migration
	Epithelial-mesenchymal transition
	Cell apoptosis
In-vitro Model	BxPC-3	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0186
	CFPAC-1	Cystic fibrosis	Homo sapiens	CVCL_1119
	MIA PaCa-2	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0428
	PANC-1	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0480

YTH domain-containing protein 1 (YTHDC1) [READER]

Regulator Info

*Representative RNA-seq result indicating the expression of this target gene regulated by YTHDC1*
Cell Line	MOLM-13 cell line	Homo sapiens
Treatment: shYTHDC1 MOLM13 cells Control: shControl MOLM13 cells		GSE168565
Regulation		logFC: 7.38E-01 p-value: 4.67E-08
More Results	Click to View More RNA-seq Results

In total 1 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene				[9]
Response Summary	YTHDC1 promoted Mutated in multiple advanced cancers 1 (PTEN) mRNA degradation to increase Akt phosphorylation, thus facilitating neuronal survival in particular after ischemia, modulating m6A reader YTHDC1 provide a potential therapeutic target for ischemic stroke.
Target Regulation	Down regulation
Responsed Disease	Acute ischemic stroke		ICD-11: 8B11	Disease Info
In-vitro Model	HEK293T	Normal	Homo sapiens	CVCL_0063
In-vivo Model	Male SD rats weighing 200-250 g were anesthetized using 4% isoflurane in 70% N₂O and 30% O₂ with a mask. A midline incision was made in the neck, the left external carotid artery (ECA) was carefully exposed and dissected, a monofilament nylon suture with a diameter of about 0.22 mm was inserted from the ECA into the internal carotid artery, and the left middle cerebral artery (MCA) was blocked. After occlusion for 90 minutes, the suture was removed for reperfusion, and ECA was ligated to close the wound. Sham-operated rats underwent the same surgery except for suture insertion. Rats were maintained on top of a warming pad (RWD, 69003) during the above procedures. The breathing machine was used to monitor the respiration of rats. The rats were returned to a heated cage during the recovery phase with free access to food and water.

YTH domain-containing family protein 1 (YTHDF1) [READER]

Regulator Info

In total 1 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene			[6]
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.
Target Regulation	Up regulation
Responsed Disease	Renal cell carcinoma of kidney	ICD-11: 2C90.0	Disease Info
Pathway Response	PI3K-Akt signaling pathway		hsa04151

YTH domain-containing family protein 2 (YTHDF2) [READER]

Regulator Info

In total 1 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene			[4]
Response Summary	METTL3/YTHDF2/Mutated in multiple advanced cancers 1 (PTEN) axis exerts a significant role in hypoxia induced PASMCs proliferation, providing a novel therapeutic target for hypoxic pulmonary hypertension.
Target Regulation	Down regulation
Responsed Disease	Pulmonary hypertension due to lung disease or hypoxia	ICD-11: BB01.2	Disease Info
Pathway Response	PI3K-Akt signaling pathway		hsa04151
Cell Process	Cell apoptosis
In-vitro Model	PASMC cell line (Pulmonary artery smooth muscle cell)
In-vivo Model	10 rats were divided into control and HPH group. In detail, 5 rats of the hypoxia groups were exposed to hypoxia (10%O₂) chamber (AiPu XBS-02B, China) for 4 weeks. In addition, 5 rats of control group were kept under normoxic conditions (21% O₂) for 4 weeks. Rats were housed in standard polypropylene cages under controlled photocycle (12 h light/12 h dark) under 22-25 ℃ temperature.

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

Disease Info

In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response		[]
Response Summary	In this review, we discuss the specific roles of m6A "writers", "erasers", and "readers" in normal physiology and how their altered expression promotes tumorigenesis. We also describe the potential of exploiting the aberrant expression of these enzymes for cancer diagnosis, prognosis, and the development of novel therapies. The abnormal expression of m6A regulatory enzymes affects m6A abundance and consequently dysregulates the expression of tumor suppressor genes and oncogenes, including MYC, SOCS2, ADAM19, and Mutated in multiple advanced cancers 1 (PTEN).
Responsed Disease	Solid tumour/cancer [ICD-11: 2A00-2F9Z]

Acute myeloid leukaemia [ICD-11: 2A60]

Disease Info

In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response			[1]
Response Summary	METTL3 depletion in human myeloid leukemia cell lines induces cell differentiation and apoptosis and delays leukemia progression in recipient mice in vivo. Single-nucleotide-resolution mapping of m6A coupled with ribosome profiling reveals that m6A promotes the translation of c-MYC, BCL2 and Mutated in multiple advanced cancers 1 (PTEN) mRNAs in the human acute myeloid leukemia MOLM-13 cell line. Moreover, loss of METTL3 leads to increased levels of phosphorylated AKT.
Responsed Disease	Acute myeloid leukaemia [ICD-11: 2A60]
Target Regulator	Methyltransferase-like 3 (METTL3)	WRITER	Regulator Info
Target Regulation	Up regulation
Cell Process	Cell differentiation and apoptosis
	Apoptosis (hsa04210)
In-vitro Model	HSPC (Human hematopoietic stem cell)
In-vivo Model	500,000 selected cells were injected via tail vein or retro-orbital route into female NSG (6-8 week old) recipient mice that had been sublethally irradiated with 475 cGy one day before transplantation.

Malignant haematopoietic neoplasm [ICD-11: 2B33]

Disease Info

In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response				[2]
Response Summary	The molecular mechanism underlying the effect of LINC00470 on chronic myelocytic leukaemia by reducing the Mutated in multiple advanced cancers 1 (PTEN) stability via RNA methyltransferase METTL3, thus leading to the inhibition of cell autophagy while promoting chemoresistance in CML.
Responsed Disease	Chronic myeloid leukaemia [ICD-11: 2B33.2]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Down regulation
Pathway Response	Autophagy			hsa04140
Cell Process	RNA stability
	Cell autophagy
In-vitro Model	K-562	Chronic myelogenous leukemia	Homo sapiens	CVCL_0004
	KCL-22	Chronic myelogenous leukemia	Homo sapiens	CVCL_2091
In-vivo Model	In the control mice or ADR mice group, the parental or chemo-resistant K562 cells were infected with LV-shCtrl. In the ADR + shLINC00470 group, the chemo-resistant K562 cells were infected with LV- shLINC00470. These cells were injected, respectively, into these 5-week-old mice subcutaneously.

Gastric cancer [ICD-11: 2B72]

Disease Info

In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response				[5]
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.
Responsed Disease	Gastric cancer [ICD-11: 2B72.Z]
Target Regulator	Methyltransferase-like 14 (METTL14)		WRITER	Regulator Info
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.

Pancreatic cancer [ICD-11: 2C10]

Disease Info

In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response				[8]
Response Summary	ALKBH5-mediated m6A demethylation enhanced the stability of KCNK15-AS1. In pancreatic cancer, KCNK15-AS1 bound to KCNK15 to inhibit its translation, and interacted with MDM2 to induce REST ubiquitination, which eventually facilitated Mutated in multiple advanced cancers 1 (PTEN) transcription to inactivate AKT pathway.
Responsed Disease	Pancreatic cancer [ICD-11: 2C10]
Target Regulator	RNA demethylase ALKBH5 (ALKBH5)		ERASER	Regulator Info
Pathway Response	.PI3K-Akt signaling pathway			hsa04151
Cell Process	Cell proliferation
	Cell migration
	Epithelial-mesenchymal transition
	Cell apoptosis
In-vitro Model	BxPC-3	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0186
	CFPAC-1	Cystic fibrosis	Homo sapiens	CVCL_1119
	MIA PaCa-2	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0428
	PANC-1	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0480

Lung cancer [ICD-11: 2C25]

Disease Info

In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response				[3]
Response Summary	Bete-elemene exerted the restrictive impacts on the cell growth of lung cancer in vivo and in vitro through targeting METTL3. Bete-elemene contributed to the augmented PTEN expression via suppressing its m6A modification.
Responsed Disease	Lung cancer [ICD-11: 2C25]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Down regulation
In-vitro Model	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
In-vivo Model	Four-week-old BALB/c nude mice were randomly divided into three groups: (1) vector group, (2) vector + Bete-elemene group, and (3) Bete-elemene + METTL3 group. Nude mice were raised in an SPF level animal house and were free to eat and drink. Mice in the vector group were subcutaneously injected with lung cancer cells transfected with empty vector and did not receive Bete-elemene administration, and this group was implemented as the negative control. Following establishing orthotopic xenografts by using A549 or H1299 cells transfected with empty vector, mice in the vector + Bete-elemene group underwent intraperitoneal injection with Bete-elemene once a day. For the subcutaneous transplanted model, A549 or H1299 cells transfected with METTL3-overexpressing vector were inoculated into mice from the Bete-elemene + METTL3 group. Then, mice were intraperitoneally administrated with Bete-elemene once a day. Three weeks later, all the animals were euthanized with CO2. Xenografts were removed and weighted after mice were euthanatized.

Renal cell carcinoma [ICD-11: 2C90]

Disease Info

In total 2 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response			[6]
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.
Responsed Disease	Renal cell carcinoma of kidney [ICD-11: 2C90.0]
Target Regulator	Methyltransferase-like 14 (METTL14)	WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	PI3K-Akt signaling pathway		hsa04151
Experiment 2 Reporting the m6A-centered Disease Response			[6]
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.
Responsed Disease	Renal cell carcinoma of kidney [ICD-11: 2C90.0]
Target Regulator	YTH domain-containing family protein 1 (YTHDF1)	READER	Regulator Info
Target Regulation	Up regulation
Pathway Response	PI3K-Akt signaling pathway		hsa04151

Acute ischemic stroke [ICD-11: 8B11]

Disease Info

In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response				[9]
Response Summary	YTHDC1 promoted Mutated in multiple advanced cancers 1 (PTEN) mRNA degradation to increase Akt phosphorylation, thus facilitating neuronal survival in particular after ischemia, modulating m6A reader YTHDC1 provide a potential therapeutic target for ischemic stroke.
Responsed Disease	Acute ischemic stroke [ICD-11: 8B11]
Target Regulator	YTH domain-containing protein 1 (YTHDC1)		READER	Regulator Info
Target Regulation	Down regulation
In-vitro Model	HEK293T	Normal	Homo sapiens	CVCL_0063
In-vivo Model	Male SD rats weighing 200-250 g were anesthetized using 4% isoflurane in 70% N₂O and 30% O₂ with a mask. A midline incision was made in the neck, the left external carotid artery (ECA) was carefully exposed and dissected, a monofilament nylon suture with a diameter of about 0.22 mm was inserted from the ECA into the internal carotid artery, and the left middle cerebral artery (MCA) was blocked. After occlusion for 90 minutes, the suture was removed for reperfusion, and ECA was ligated to close the wound. Sham-operated rats underwent the same surgery except for suture insertion. Rats were maintained on top of a warming pad (RWD, 69003) during the above procedures. The breathing machine was used to monitor the respiration of rats. The rats were returned to a heated cage during the recovery phase with free access to food and water.

Pulmonary hypertension [ICD-11: BB01]

Disease Info

In total 2 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response			[4]
Response Summary	METTL3/YTHDF2/Mutated in multiple advanced cancers 1 (PTEN) axis exerts a significant role in hypoxia induced PASMCs proliferation, providing a novel therapeutic target for hypoxic pulmonary hypertension.
Responsed Disease	Pulmonary hypertension due to lung disease or hypoxia [ICD-11: BB01.2]
Target Regulator	Methyltransferase-like 3 (METTL3)	WRITER	Regulator Info
Target Regulation	Down regulation
Pathway Response	PI3K-Akt signaling pathway		hsa04151
Cell Process	Cell apoptosis
In-vitro Model	PASMC cell line (Pulmonary artery smooth muscle cell)
In-vivo Model	10 rats were divided into control and HPH group. In detail, 5 rats of the hypoxia groups were exposed to hypoxia (10%O₂) chamber (AiPu XBS-02B, China) for 4 weeks. In addition, 5 rats of control group were kept under normoxic conditions (21% O₂) for 4 weeks. Rats were housed in standard polypropylene cages under controlled photocycle (12 h light/12 h dark) under 22-25 ℃ temperature.
Experiment 2 Reporting the m6A-centered Disease Response			[4]
Response Summary	METTL3/YTHDF2/Mutated in multiple advanced cancers 1 (PTEN) axis exerts a significant role in hypoxia induced PASMCs proliferation, providing a novel therapeutic target for hypoxic pulmonary hypertension.
Responsed Disease	Pulmonary hypertension due to lung disease or hypoxia [ICD-11: BB01.2]
Target Regulator	YTH domain-containing family protein 2 (YTHDF2)	READER	Regulator Info
Target Regulation	Down regulation
Pathway Response	PI3K-Akt signaling pathway		hsa04151
Cell Process	Cell apoptosis
In-vitro Model	PASMC cell line (Pulmonary artery smooth muscle cell)
In-vivo Model	10 rats were divided into control and HPH group. In detail, 5 rats of the hypoxia groups were exposed to hypoxia (10%O₂) chamber (AiPu XBS-02B, China) for 4 weeks. In addition, 5 rats of control group were kept under normoxic conditions (21% O₂) for 4 weeks. Rats were housed in standard polypropylene cages under controlled photocycle (12 h light/12 h dark) under 22-25 ℃ temperature.

Chronic kidney disease [ICD-11: GB61]

Disease Info

In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response				[7]
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.
Responsed Disease	Chronic kidney disease [ICD-11: GB61.Z]
Target Regulator	Methyltransferase-like 14 (METTL14)		WRITER	Regulator Info
Target Regulation	Down regulation
Pathway Response	PI3K-Akt signaling pathway			hsa04151
Cell Process	Epithelial-mesenchymal transition
In-vitro Model	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).

References

Ref 1	The N(6)-methyladenosine (m(6)A)-forming enzyme METTL3 controls myeloid differentiation of normal hematopoietic and leukemia cells. Nat Med. 2017 Nov;23(11):1369-1376. doi: 10.1038/nm.4416. Epub 2017 Sep 18.
Ref 2	Dysregulation of LINC00470 and METTL3 promotes chemoresistance and suppresses autophagy of chronic myelocytic leukaemia cells. J Cell Mol Med. 2021 May;25(9):4248-4259. doi: 10.1111/jcmm.16478. Epub 2021 Mar 21.
Ref 3	Beta-Elemene Restrains PTEN mRNA Degradation to Restrain the Growth of Lung Cancer Cells via METTL3-Mediated N(6) Methyladenosine Modification. J Oncol. 2022 Jan 12;2022:3472745. doi: 10.1155/2022/3472745. eCollection 2022.
Ref 4	The m(6)A methyltransferase METTL3 promotes hypoxic pulmonary arterial hypertension. Life Sci. 2021 Jun 1;274:119366. doi: 10.1016/j.lfs.2021.119366. Epub 2021 Mar 16.
Ref 5	The m6A Methyltransferase METTL14-Mediated N6-Methyladenosine Modification of PTEN mRNA Inhibits Tumor Growth and Metastasis in Stomach Adenocarcinoma. Front Oncol. 2021 Aug 12;11:699749. doi: 10.3389/fonc.2021.699749. eCollection 2021.
Ref 6	METTL14-mediated N6-methyladenosine modification of Pten mRNA inhibits tumour progression in clear-cell renal cell carcinoma. Br J Cancer. 2022 Jul;127(1):30-42. doi: 10.1038/s41416-022-01757-y. Epub 2022 Mar 5.
Ref 7	METTL14-regulated PI3K/Akt signaling pathway via PTEN affects HDAC5-mediated epithelial-mesenchymal transition of renal tubular cells in diabetic kidney disease. Cell Death Dis. 2021 Jan 4;12(1):32. doi: 10.1038/s41419-020-03312-0.
Ref 8	ALKBH5-mediated m(6)A demethylation of KCNK15-AS1 inhibits pancreatic cancer progression via regulating KCNK15 and PTEN/AKT signaling. Cell Death Dis. 2021 Dec 1;12(12):1121. doi: 10.1038/s41419-021-04401-4.
Ref 9	YTHDC1 mitigates ischemic stroke by promoting Akt phosphorylation through destabilizing PTEN mRNA. Cell Death Dis. 2020 Nov 13;11(11):977. doi: 10.1038/s41419-020-03186-2.

m6A Target Gene Information

Cite M6AREG

Correspondence

Prof. Feng ZHU

Prof. Shuiping Liu

Visitor Map