m6A Target Gene Information

General Information of the m6A Target Gene (ID: M6ATAR00368)
Target Name PI3-kinase subunit alpha (PI3k/PIK3CA)
Synonyms
PI3-kinase subunit alpha; PI3K-alpha; PI3Kalpha; PtdIns-3-kinase subunit alpha; Phosphatidylinositol 4,5-bisphosphate 3-kinase 110 kDa catalytic subunit alpha; PtdIns-3-kinase subunit p110-alpha; p110alpha; Phosphoinositide 3-kinase alpha; Phosphoinositide-3-kinase catalytic alpha polypeptide; Serine/threonine protein kinase PIK3CA
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Gene Name PIK3CA
Chromosomal Location 3q26.32
Family PI3/PI4-kinase family
Function
Phosphoinositide-3-kinase (PI3K) phosphorylates phosphatidylinositol (PI) and its phosphorylated derivatives at position 3 of the inositol ring to produce 3-phosphoinositides. Uses ATP and PtdIns(4,5)P2 (phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Participates in cellular signaling in response to various growth factors. Involved in the activation of AKT1 upon stimulation by receptor tyrosine kinases ligands such as EGF, insulin, IGF1, VEGFA and PDGF. Involved in signaling via insulin-receptor substrate (IRS) proteins. Essential in endothelial cell migration during vascular development through VEGFA signaling, possibly by regulating RhoA activity. Required for lymphatic vasculature development, possibly by binding to RAS and by activation by EGF and FGF2, but not by PDGF. Regulates invadopodia formation through the PDPK1-AKT1 pathway. Participates in cardiomyogenesis in embryonic stem cells through a AKT1 pathway. Participates in vasculogenesis in embryonic stem cells through PDK1 and protein kinase C pathway. In addition to its lipid kinase activity, it displays a serine-protein kinase activity that results in the autophosphorylation of the p85alpha regulatory subunit as well as phosphorylation of other proteins such as 4EBP1, H-Ras, the IL-3 beta c receptor and possibly others. Plays a role in the positive regulation of phagocytosis and pinocytosis (By similarity).
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Gene ID 5290
Uniprot ID
PK3CA_HUMAN
HGNC ID
HGNC:8975
Ensembl Gene ID
ENSG00000121879
KEGG ID
hsa:5290
Full List of m6A Methylation Regulator of This Target Gene and Corresponding Disease/Drug Response(s)
PIK3CA 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 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: -6.28E-01
p-value: 7.56E-03
More Results Click to View More RNA-seq Results
In total 2 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [1]
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.
Target Regulation Down regulation
Responsed Disease Gastric cancer ICD-11: 2B72
 Disease Info 
Pathway Response PI3K-Akt signaling pathway hsa04151
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
Experiment 2 Reporting the m6A Methylation Regulator of This Target Gene [2]
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.
Target Regulation Down regulation
Responsed Disease Hepatocellular carcinoma ICD-11: 2C12.02
 Disease Info 
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.
Methyltransferase-like 3 (METTL3) [WRITER]
 Regulator Info 
Representative RNA-seq result indicating the expression of this target gene regulated by METTL3
Cell Line HULEC-5a cell line Homo sapiens
Treatment: METTL3 knockdown HULEC-5a cells
Control: HULEC-5a cells
 GSE200649
Regulation
logFC: -2.36E+00
p-value: 7.04E-03
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 [3]
Response Summary miR-600 inhibited lung cancer via down-regulating METTL3 expression, and knockdown of METTL3 was used as a novel strategy for lung cancer therapy. The PI3-kinase subunit alpha (PI3k/PIK3CA)/Akt pathway is implicated in cell growth and survival and we also observed that knockdown of METTL3 changed the expression and phosphorylation of proteins of PI3K signaling pathway members.
Target Regulation Up regulation
Responsed Disease Lung cancer ICD-11: 2C25
 Disease Info 
Pathway Response Apoptosis hsa04210
PI3K-Akt signaling pathway hsa04151
Cell Process Cell proliferation
In-vitro Model A-549 Lung adenocarcinoma Homo sapiens CVCL_0023
NCI-H1299 Lung large cell carcinoma Homo sapiens CVCL_0060
Experiment 2 Reporting the m6A Methylation Regulator of This Target Gene [4]
Response Summary METTL3-mediated m6 A methylation promotes lung cancer progression via activating PI3-kinase subunit alpha (PI3k/PIK3CA)/AKT/mTOR pathway.
Target Regulation Up regulation
Responsed Disease Lung cancer ICD-11: 2C25
 Disease Info 
Pathway Response mTOR signaling pathway hsa04150
PI3K-Akt signaling pathway hsa04151
In-vitro Model A-549 Lung adenocarcinoma Homo sapiens CVCL_0023
In-vivo Model 5 × 106 A549 cells overexpressing METTL3 (Lv-METTL3) or control (Lv-Ctrl) were suspended in 100?uL phosphate-buffered saline (PBS), and were subcutaneously injected into mouse lower right flank. Drug treatment started in the Lv-METTL3 group when the tumour volume reached around 100 mm3. Mice were randomly divided into three groups to receive vehicle, GSK2536771 (30 mg/kg) or rapamycin (1 mg/kg). Drugs were administrated daily through intraperitoneal injection for 18 days. Treatment conditions were chosen as previously reported.
Experiment 3 Reporting the m6A Methylation Regulator of This Target Gene [5]
Response Summary Knockdown of METTL3 could obviously promote cell proliferation, migration and invasion function, and induce G0/G1 arrest,METTL3 acts as a novel marker for tumorigenesis, development and survival of RCC. Knockdown of METTL3 promoted changes in PI3-kinase subunit alpha (PI3k/PIK3CA)/AKT/mTOR markers' expression with a gain in p-PI3k, p-AKT, p-mTOR and p-p70, and a loss of p-4EBP1.
Target Regulation Down regulation
Responsed Disease Renal cell carcinoma ICD-11: 2C90
 Disease Info 
Cell Process Epithelial-to-mesenchymal transition
Arrest cell cycle at G0/G1 phase
In-vitro Model ACHN Papillary renal cell carcinoma Homo sapiens CVCL_1067
Caki-1 Clear cell renal cell carcinoma Homo sapiens CVCL_0234
Caki-2 Papillary renal cell carcinoma Homo sapiens CVCL_0235
HK2 Normal Acipenser baerii CVCL_YE28
In-vivo Model Cells (5×106 cells in 200 uL) were suspended with 100 uL PBS and 100 uL Matrigel Matrix, and injected subcutaneously into the left armpit of each mouse.
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: -2.12E+00
p-value: 2.82E-03
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 [6]
Response Summary ALKBH5 is a tumor-promoting gene in epithelial ovarian cancer, which is involved in the mTOR pathway and BCL-2-Beclin1 complex. ALKBH5 activated EGFR-PI3-kinase subunit alpha (PI3k/PIK3CA)-AKT-mTOR signaling pathway. ALKBH5 inhibited autophagy of epithelial ovarian cancer through miR-7 and BCL-2.
Target Regulation Up regulation
Responsed Disease Ovarian cancer ICD-11: 2C73
 Disease Info 
Pathway Response PI3K-Akt signaling pathway hsa04151
mTOR signaling pathway hsa04150
Autophagy hsa04140
In-vitro Model A2780 Ovarian endometrioid adenocarcinoma Homo sapiens CVCL_0134
CoC1 Ovarian adenocarcinoma Homo sapiens CVCL_6891
OVCAR-3 Ovarian serous adenocarcinoma Homo sapiens CVCL_0465
SK-OV-3 Ovarian serous cystadenocarcinoma Homo sapiens CVCL_0532
In-vivo Model SKOV3 or A2780 cells were infected with the indicated lentiviral vectors and injected (5 × 106 cells/mouse in 200 uL volume) subcutaneously into the left armpit of 6-week-old BALB/c nude mice. After 21 days, the animals were sacrificed to confirm the presence of tumors and weigh the established tumors
Gastric cancer [ICD-11: 2B72]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [1]
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.
Responsed Disease Gastric cancer [ICD-11: 2B72]
Target Regulator Methyltransferase-like 14 (METTL14) WRITER
 Regulator Info 
Target Regulation Down regulation
Pathway Response PI3K-Akt signaling pathway hsa04151
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
Gastrointestinal cancer [ICD-11: 2C11]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response []
Response Summary m6A regulators were mostly upregulated in Gastrointestinal cancer and their differential expression significantly influenced the overall survival of patients with GI cancer. The PI3-kinase subunit alpha (PI3k/PIK3CA)/Akt and mammalian target of rapamycin (mTOR) signaling pathways were found to be potentially affected by m6A modification in most human cancers, including GI cancer, which was further verified by m6A-Seq and phospho-MAPK array.
Responsed Disease Gastrointestinal cancer [ICD-11: 2C11]
Pathway Response PI3K-Akt signaling pathway hsa04151), mTOR signaling pathway
In-vitro Model ()
()
()
()
Liver cancer [ICD-11: 2C12]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [2]
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.
Responsed Disease Hepatocellular carcinoma [ICD-11: 2C12.02]
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 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.
Lung cancer [ICD-11: 2C25]
 Disease Info 
In total 2 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [3]
Response Summary miR-600 inhibited lung cancer via down-regulating METTL3 expression, and knockdown of METTL3 was used as a novel strategy for lung cancer therapy. The PI3-kinase subunit alpha (PI3k/PIK3CA)/Akt pathway is implicated in cell growth and survival and we also observed that knockdown of METTL3 changed the expression and phosphorylation of proteins of PI3K signaling pathway members.
Responsed Disease Lung cancer [ICD-11: 2C25]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Up regulation
Pathway Response Apoptosis hsa04210
PI3K-Akt signaling pathway hsa04151
Cell Process Cell proliferation
In-vitro Model A-549 Lung adenocarcinoma Homo sapiens CVCL_0023
NCI-H1299 Lung large cell carcinoma Homo sapiens CVCL_0060
Experiment 2 Reporting the m6A-centered Disease Response [4]
Response Summary METTL3-mediated m6 A methylation promotes lung cancer progression via activating PI3-kinase subunit alpha (PI3k/PIK3CA)/AKT/mTOR pathway.
Responsed Disease Lung cancer [ICD-11: 2C25]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Up regulation
Pathway Response mTOR signaling pathway hsa04150
PI3K-Akt signaling pathway hsa04151
In-vitro Model A-549 Lung adenocarcinoma Homo sapiens CVCL_0023
In-vivo Model 5 × 106 A549 cells overexpressing METTL3 (Lv-METTL3) or control (Lv-Ctrl) were suspended in 100?uL phosphate-buffered saline (PBS), and were subcutaneously injected into mouse lower right flank. Drug treatment started in the Lv-METTL3 group when the tumour volume reached around 100 mm3. Mice were randomly divided into three groups to receive vehicle, GSK2536771 (30 mg/kg) or rapamycin (1 mg/kg). Drugs were administrated daily through intraperitoneal injection for 18 days. Treatment conditions were chosen as previously reported.
Ovarian cancer [ICD-11: 2C73]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [6]
Response Summary ALKBH5 is a tumor-promoting gene in epithelial ovarian cancer, which is involved in the mTOR pathway and BCL-2-Beclin1 complex. ALKBH5 activated EGFR-PI3-kinase subunit alpha (PI3k/PIK3CA)-AKT-mTOR signaling pathway. ALKBH5 inhibited autophagy of epithelial ovarian cancer through miR-7 and BCL-2.
Responsed Disease Ovarian cancer [ICD-11: 2C73]
Target Regulator RNA demethylase ALKBH5 (ALKBH5) ERASER
 Regulator Info 
Target Regulation Up regulation
Pathway Response PI3K-Akt signaling pathway hsa04151
mTOR signaling pathway hsa04150
Autophagy hsa04140
In-vitro Model A2780 Ovarian endometrioid adenocarcinoma Homo sapiens CVCL_0134
CoC1 Ovarian adenocarcinoma Homo sapiens CVCL_6891
OVCAR-3 Ovarian serous adenocarcinoma Homo sapiens CVCL_0465
SK-OV-3 Ovarian serous cystadenocarcinoma Homo sapiens CVCL_0532
In-vivo Model SKOV3 or A2780 cells were infected with the indicated lentiviral vectors and injected (5 × 106 cells/mouse in 200 uL volume) subcutaneously into the left armpit of 6-week-old BALB/c nude mice. After 21 days, the animals were sacrificed to confirm the presence of tumors and weigh the established tumors
Renal cell carcinoma [ICD-11: 2C90]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [5]
Response Summary Knockdown of METTL3 could obviously promote cell proliferation, migration and invasion function, and induce G0/G1 arrest,METTL3 acts as a novel marker for tumorigenesis, development and survival of RCC. Knockdown of METTL3 promoted changes in PI3-kinase subunit alpha (PI3k/PIK3CA)/AKT/mTOR markers' expression with a gain in p-PI3k, p-AKT, p-mTOR and p-p70, and a loss of p-4EBP1.
Responsed Disease Renal cell carcinoma [ICD-11: 2C90]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Down regulation
Cell Process Epithelial-to-mesenchymal transition
Arrest cell cycle at G0/G1 phase
In-vitro Model ACHN Papillary renal cell carcinoma Homo sapiens CVCL_1067
Caki-1 Clear cell renal cell carcinoma Homo sapiens CVCL_0234
Caki-2 Papillary renal cell carcinoma Homo sapiens CVCL_0235
HK2 Normal Acipenser baerii CVCL_YE28
In-vivo Model Cells (5×106 cells in 200 uL) were suspended with 100 uL PBS and 100 uL Matrigel Matrix, and injected subcutaneously into the left armpit of each mouse.
References
Ref 1 The m6A methyltransferase METTL14 inhibits the proliferation, migration, and invasion of gastric cancer by regulating the PI3K/AKT/mTOR signaling pathway. J Clin Lab Anal. 2021 Mar;35(3):e23655. doi: 10.1002/jcla.23655. Epub 2020 Dec 12.
Ref 2 METTL14 Inhibits Hepatocellular Carcinoma Metastasis Through Regulating EGFR/PI3K/AKT Signaling Pathway in an m6A-Dependent Manner. Cancer Manag Res. 2020 Dec 23;12:13173-13184. doi: 10.2147/CMAR.S286275. eCollection 2020.
Ref 3 miR-600 inhibits lung cancer via downregulating the expression of METTL3. Cancer Manag Res. 2019 Feb 1;11:1177-1187. doi: 10.2147/CMAR.S181058. eCollection 2019.
Ref 4 Methyltransferase-like 3 promotes the progression of lung cancer via activating PI3K/AKT/mTOR pathway. Clin Exp Pharmacol Physiol. 2022 Jul;49(7):748-758. doi: 10.1111/1440-1681.13647. Epub 2022 May 23.
Ref 5 The M6A methyltransferase METTL3: acting as a tumor suppressor in renal cell carcinoma. Oncotarget. 2017 Oct 10;8(56):96103-96116. doi: 10.18632/oncotarget.21726. eCollection 2017 Nov 10.
Ref 6 ALKBH5 inhibited autophagy of epithelial ovarian cancer through miR-7 and BCL-2. J Exp Clin Cancer Res. 2019 Apr 15;38(1):163. doi: 10.1186/s13046-019-1159-2.