m6A Target Gene Information

General Information of the m6A Target Gene (ID: M6ATAR00366)
Target Name PHLPP-like (PHLPP2)
Synonyms
PH domain leucine-rich repeat-containing protein phosphatase-like; PHLPP-like; KIAA0931; PHLPPL
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Gene Name PHLPP2
Chromosomal Location 16q22.2
Function
Protein phosphatase involved in regulation of Akt and PKC signaling. Mediates dephosphorylation in the C-terminal domain hydrophobic motif of members of the AGC Ser/Thr protein kinase family; specifically acts on 'Ser-473' of AKT1, 'Ser-660' of PRKCB isoform beta-II and 'Ser-657' of PRKCA. Akt regulates the balance between cell survival and apoptosis through a cascade that primarily alters the function of transcription factors that regulate pro- and antiapoptotic genes. Dephosphorylation of 'Ser-473' of Akt triggers apoptosis and decreases cell proliferation. Also controls the phosphorylation of AKT3. Dephosphorylates STK4 on 'Thr-387' leading to STK4 activation and apoptosis. Dephosphorylates RPS6KB1 and is involved in regulation of cap-dependent translation. Inhibits cancer cell proliferation and may act as a tumor suppressor. Dephosphorylation of PRKCA and PRKCB leads to their destabilization and degradation. Dephosphorylates RAF1 inhibiting its kinase activity.
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Gene ID 23035
Uniprot ID
PHLP2_HUMAN
HGNC ID
HGNC:29149
Ensembl Gene ID
ENSG00000040199
KEGG ID
hsa:23035
Full List of m6A Methylation Regulator of This Target Gene and Corresponding Disease/Drug Response(s)
PHLPP2 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 MDA-MB-231 Homo sapiens
Treatment: METTL3 knockdown MDA-MB-231 cells
Control: MDA-MB-231 cells
 GSE70061
Regulation
logFC: 7.59E-01
p-value: 9.18E-03
More Results Click to View More RNA-seq Results
Representative RIP-seq result supporting the interaction between PHLPP2 and the regulator
Cell Line MDA-MB-231 Homo sapiens
Regulation logFC: 1.40E+00 GSE60213
In total 1 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [1]
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.
Target Regulation Up regulation
Responsed Disease Endometrial cancer ICD-11: 2C76
 Disease Info 
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 (Foxn1nu, Harlan; n=10 per group).
Methyltransferase-like 14 (METTL14) [WRITER]
 Regulator Info 
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
In total 1 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [1]
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.
Target Regulation Up regulation
Responsed Disease Endometrial cancer ICD-11: 2C76
 Disease Info 
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 (Foxn1nu, Harlan; n=10 per group).
Endometrial cancer [ICD-11: 2C76]
 Disease Info 
In total 2 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [1]
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.
Responsed Disease Endometrial cancer [ICD-11: 2C76]
Target Regulator Methyltransferase-like 14 (METTL14) WRITER
 Regulator Info 
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 (Foxn1nu, Harlan; n=10 per group).
Experiment 2 Reporting the m6A-centered Disease Response [1]
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.
Responsed Disease Endometrial cancer [ICD-11: 2C76]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
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 (Foxn1nu, Harlan; n=10 per group).
References
Ref 1 m(6)A mRNA methylation regulates AKT activity to promote the proliferation and tumorigenicity of endometrial cancer. Nat Cell Biol. 2018 Sep;20(9):1074-1083. doi: 10.1038/s41556-018-0174-4. Epub 2018 Aug 27.