Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZSUQK5)

• DOT Name: Phosphatidylinositol 3-kinase regulatory subunit beta (PIK3R2)
• Synonyms: PI3-kinase regulatory subunit beta; PI3K regulatory subunit beta; PtdIns-3-kinase regulatory subunit beta; Phosphatidylinositol 3-kinase 85 kDa regulatory subunit beta; PI3-kinase subunit p85-beta; PtdIns-3-kinase regulatory subunit p85-beta
• Gene Name: PIK3R2
• Related Disease:
  Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1
  Overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes
  Adenocarcinoma
  Adult glioblastoma
  Alzheimer disease
  Bilateral perisylvian polymicrogyria
  Brain disease
  Breast cancer
  Classic Hodgkin lymphoma
  Colon cancer
  Colon carcinoma
  Diabetic kidney disease
  Esophageal squamous cell carcinoma
  Glioblastoma multiforme
  Head and neck cancer
  Head and neck carcinoma
  Hepatocellular carcinoma
  HIV infectious disease
  Lung cancer
  Lung carcinoma
  Lung squamous cell carcinoma
  Malignant glioma
  Mood disorder
  Nasopharyngeal carcinoma
  Neoplasm
  Neuroblastoma
  Non-small-cell lung cancer
  Plasma cell myeloma
  Polydactyly
  Prostate carcinoma
  Prostate neoplasm
  Rheumatoid arthritis
  Small lymphocytic lymphoma
  Breast carcinoma
  Clear cell renal carcinoma
  Colorectal carcinoma
  Endometrial cancer
  Endometrial carcinoma
  Kidney cancer
  leukaemia
  Leukemia
  Megalencephaly-capillary malformation-polymicrogyria syndrome
  Prostate cancer
  Renal carcinoma
  Renal cell carcinoma
  Megalencephaly-polymicrogyria-postaxial polydactyly-hydrocephalus syndrome
  Megalencephaly
  Hepatitis C virus infection
  Kaposi sarcoma
  Mesothelioma
• UniProt ID: P85B_HUMAN
• PDB ID: 2KT1; 2XS6; 3MTT; 3O5Z; 6OX7; 6U28; 7RCH; 7RNU
• Pfam ID: PF16454 ; PF00620 ; PF00017
• Sequence:
  MAGPEGFQYRALYPFRRERPEDLELLPGDVLVVSRAALQALGVAEGGERCPQSVGWMPGL
  NERTRQRGDFPGTYVEFLGPVALARPGPRPRGPRPLPARPRDGAPEPGLTLPDLPEQFSP
  PDVAPPLLVKLVEAIERTGLDSESHYRPELPAPRTDWSLSDVDQWDTAALADGIKSFLLA
  LPAPLVTPEASAEARRALREAAGPVGPALEPPTLPLHRALTLRFLLQHLGRVASRAPALG
  PAVRALGATFGPLLLRAPPPPSSPPPGGAPDGSEPSPDFPALLVEKLLQEHLEEQEVAPP
  ALPPKPPKAKPASTVLANGGSPPSLQDAEWYWGDISREEVNEKLRDTPDGTFLVRDASSK
  IQGEYTLTLRKGGNNKLIKVFHRDGHYGFSEPLTFCSVVDLINHYRHESLAQYNAKLDTR
  LLYPVSKYQQDQIVKEDSVEAVGAQLKVYHQQYQDKSREYDQLYEEYTRTSQELQMKRTA
  IEAFNETIKIFEEQGQTQEKCSKEYLERFRREGNEKEMQRILLNSERLKSRIAEIHESRT
  KLEQQLRAQASDNREIDKRMNSLKPDLMQLRKIRDQYLVWLTQKGARQKKINEWLGIKNE
  TEDQYALMEDEDDLPHHEERTWYVGKINRTQAEEMLSGKRDGTFLIRESSQRGCYACSVV
  VDGDTKHCVIYRTATGFGFAEPYNLYGSLKELVLHYQHASLVQHNDALTVTLAHPVRAPG
  PGPPPAAR
• Function: Regulatory subunit of phosphoinositide-3-kinase (PI3K), a kinase that phosphorylates 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. Binds to activated (phosphorylated) protein-tyrosine kinases, through its SH2 domain, and acts as an adapter, mediating the association of the p110 catalytic unit to the plasma membrane. Indirectly regulates autophagy. Promotes nuclear translocation of XBP1 isoform 2 in a ER stress- and/or insulin-dependent manner during metabolic overloading in the liver and hence plays a role in glucose tolerance improvement.
• KEGG Pathway:
  EGFR tyrosine ki.se inhibitor resistance (hsa01521)
  Endocrine resistance (hsa01522)
  Platinum drug resistance (hsa01524)
  ErbB sig.ling pathway (hsa04012)
  Ras sig.ling pathway (hsa04014)
  Rap1 sig.ling pathway (hsa04015)
  cAMP sig.ling pathway (hsa04024)
  Chemokine sig.ling pathway (hsa04062)
  HIF-1 sig.ling pathway (hsa04066)
  FoxO sig.ling pathway (hsa04068)
  Phosphatidylinositol sig.ling system (hsa04070)
  Sphingolipid sig.ling pathway (hsa04071)
  Phospholipase D sig.ling pathway (hsa04072)
  Autophagy - animal (hsa04140)
  mTOR sig.ling pathway (hsa04150)
  PI3K-Akt sig.ling pathway (hsa04151)
  AMPK sig.ling pathway (hsa04152)
  Apoptosis (hsa04210)
  Longevity regulating pathway (hsa04211)
  Longevity regulating pathway - multiple species (hsa04213)
  Cellular senescence (hsa04218)
  Axon guidance (hsa04360)
  VEGF sig.ling pathway (hsa04370)
  Osteoclast differentiation (hsa04380)
  Focal adhesion (hsa04510)
  Sig.ling pathways regulating pluripotency of stem cells (hsa04550)
  Platelet activation (hsa04611)
  Neutrophil extracellular trap formation (hsa04613)
  Toll-like receptor sig.ling pathway (hsa04620)
  C-type lectin receptor sig.ling pathway (hsa04625)
  JAK-STAT sig.ling pathway (hsa04630)
  .tural killer cell mediated cytotoxicity (hsa04650)
  T cell receptor sig.ling pathway (hsa04660)
  B cell receptor sig.ling pathway (hsa04662)
  Fc epsilon RI sig.ling pathway (hsa04664)
  Fc gamma R-mediated phagocytosis (hsa04666)
  TNF sig.ling pathway (hsa04668)
  Leukocyte transendothelial migration (hsa04670)
  Neurotrophin sig.ling pathway (hsa04722)
  Cholinergic sy.pse (hsa04725)
  Inflammatory mediator regulation of TRP channels (hsa04750)
  Regulation of actin cytoskeleton (hsa04810)
  Insulin sig.ling pathway (hsa04910)
  Progesterone-mediated oocyte maturation (hsa04914)
  Estrogen sig.ling pathway (hsa04915)
  Prolactin sig.ling pathway (hsa04917)
  Thyroid hormone sig.ling pathway (hsa04919)
  Regulation of lipolysis in adipocytes (hsa04923)
  Relaxin sig.ling pathway (hsa04926)
  GnRH secretion (hsa04929)
  Type II diabetes mellitus (hsa04930)
  Insulin resistance (hsa04931)
  Non-alcoholic fatty liver disease (hsa04932)
  AGE-RAGE sig.ling pathway in diabetic complications (hsa04933)
  Growth hormone synthesis, secretion and action (hsa04935)
  Aldosterone-regulated sodium reabsorption (hsa04960)
  Carbohydrate digestion and absorption (hsa04973)
  Alzheimer disease (hsa05010)
  Spinocerebellar ataxia (hsa05017)
  Prion disease (hsa05020)
  Bacterial invasion of epithelial cells (hsa05100)
  Shigellosis (hsa05131)
  Yersinia infection (hsa05135)
  Chagas disease (hsa05142)
  Amoebiasis (hsa05146)
  Hepatitis C (hsa05160)
  Hepatitis B (hsa05161)
  Measles (hsa05162)
  Human cytomegalovirus infection (hsa05163)
  Influenza A (hsa05164)
  Human papillomavirus infection (hsa05165)
  Human T-cell leukemia virus 1 infection (hsa05166)
  Kaposi sarcoma-associated herpesvirus infection (hsa05167)
  Herpes simplex virus 1 infection (hsa05168)
  Epstein-Barr virus infection (hsa05169)
  Human immunodeficiency virus 1 infection (hsa05170)
  Coro.virus disease - COVID-19 (hsa05171)
  Pathways in cancer (hsa05200)
  Viral carcinogenesis (hsa05203)
  Proteoglycans in cancer (hsa05205)
  MicroR.s in cancer (hsa05206)
  Chemical carcinogenesis - receptor activation (hsa05207)
  Chemical carcinogenesis - reactive oxygen species (hsa05208)
  Colorectal cancer (hsa05210)
  Re.l cell carcinoma (hsa05211)
  Pancreatic cancer (hsa05212)
  Endometrial cancer (hsa05213)
  Glioma (hsa05214)
  Prostate cancer (hsa05215)
  Melanoma (hsa05218)
  Chronic myeloid leukemia (hsa05220)
  Acute myeloid leukemia (hsa05221)
  Small cell lung cancer (hsa05222)
  Non-small cell lung cancer (hsa05223)
  Breast cancer (hsa05224)
  Hepatocellular carcinoma (hsa05225)
  Gastric cancer (hsa05226)
  Central carbon metabolism in cancer (hsa05230)
  Choline metabolism in cancer (hsa05231)
  PD-L1 expression and PD-1 checkpoint pathway in cancer (hsa05235)
  Diabetic cardiomyopathy (hsa05415)
  Lipid and atherosclerosis (hsa05417)
  Fluid shear stress and atherosclerosis (hsa05418)
• Reactome Pathway:
  IRS-mediated signalling (R-HSA-112399)
  GPVI-mediated activation cascade (R-HSA-114604)
  PIP3 activates AKT signaling (R-HSA-1257604)
  Interleukin-7 signaling (R-HSA-1266695)
  Signaling by SCF-KIT (R-HSA-1433557)
  Synthesis of PIPs at the plasma membrane (R-HSA-1660499)
  Downstream signal transduction (R-HSA-186763)
  PI3K/AKT activation (R-HSA-198203)
  Signaling by ALK (R-HSA-201556)
  Downstream TCR signaling (R-HSA-202424)
  Role of phospholipids in phagocytosis (R-HSA-2029485)
  Tie2 Signaling (R-HSA-210993)
  Constitutive Signaling by Aberrant PI3K in Cancer (R-HSA-2219530)
  DAP12 signaling (R-HSA-2424491)
  Role of LAT2/NTAL/LAB on calcium mobilization (R-HSA-2730905)
  Nephrin family interactions (R-HSA-373753)
  Costimulation by the CD28 family (R-HSA-388841)
  CD28 dependent PI3K/Akt signaling (R-HSA-389357)
  G alpha (q) signalling events (R-HSA-416476)
  VEGFA-VEGFR2 Pathway (R-HSA-4420097)
  Interleukin-3, Interleukin-5 and GM-CSF signaling (R-HSA-512988)
  RAF/MAP kinase cascade (R-HSA-5673001)
  PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling (R-HSA-6811558)
  RET signaling (R-HSA-8853659)
  RHOA GTPase cycle (R-HSA-8980692)
  Extra-nuclear estrogen signaling (R-HSA-9009391)
  RHOB GTPase cycle (R-HSA-9013026)
  CDC42 GTPase cycle (R-HSA-9013148)
  RAC1 GTPase cycle (R-HSA-9013149)
  RAC2 GTPase cycle (R-HSA-9013404)
  RHOD GTPase cycle (R-HSA-9013405)
  RHOJ GTPase cycle (R-HSA-9013409)
  RHOU GTPase cycle (R-HSA-9013420)
  RAC3 GTPase cycle (R-HSA-9013423)
  RHOF GTPase cycle (R-HSA-9035034)
  Interleukin receptor SHC signaling (R-HSA-912526)
  Regulation of signaling by CBL (R-HSA-912631)
  Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants (R-HSA-9670439)
  Signaling by PDGFRA transmembrane, juxtamembrane and kinase domain mutants (R-HSA-9673767)
  Signaling by PDGFRA extracellular domain mutants (R-HSA-9673770)
  RND3 GTPase cycle (R-HSA-9696264)
  RND2 GTPase cycle (R-HSA-9696270)
  RND1 GTPase cycle (R-HSA-9696273)
  PI3K Cascade (R-HSA-109704)
• BioCyc Pathway: MetaCyc:ENSG00000105647-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

50 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1	DIS06C5U	Definitive	Autosomal dominant	[1]
Overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes	DISWECW7	Definitive	Autosomal dominant	[2]
Adenocarcinoma	DIS3IHTY	Strong	Altered Expression	[3]
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[4]
Alzheimer disease	DISF8S70	Strong	Biomarker	[5]
Bilateral perisylvian polymicrogyria	DISIF9XK	Strong	Genetic Variation	[6]
Brain disease	DIS6ZC3X	Strong	Genetic Variation	[7]
Breast cancer	DIS7DPX1	Strong	Biomarker	[8]
Classic Hodgkin lymphoma	DISV1LU6	Strong	Altered Expression	[9]
Colon cancer	DISVC52G	Strong	Biomarker	[10]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[10]
Diabetic kidney disease	DISJMWEY	Strong	Biomarker	[11]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[12]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[4]
Head and neck cancer	DISBPSQZ	Strong	Biomarker	[13]
Head and neck carcinoma	DISOU1DS	Strong	Biomarker	[13]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[14]
HIV infectious disease	DISO97HC	Strong	Biomarker	[15]
Lung cancer	DISCM4YA	Strong	Biomarker	[3]
Lung carcinoma	DISTR26C	Strong	Biomarker	[3]
Lung squamous cell carcinoma	DISXPIBD	Strong	Biomarker	[16]
Malignant glioma	DISFXKOV	Strong	Biomarker	[17]
Mood disorder	DISLVMWO	Strong	Biomarker	[18]
Nasopharyngeal carcinoma	DISAOTQ0	Strong	Biomarker	[19]
Neoplasm	DISZKGEW	Strong	Biomarker	[20]
Neuroblastoma	DISVZBI4	Strong	Altered Expression	[5]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[21]
Plasma cell myeloma	DIS0DFZ0	Strong	Biomarker	[22]
Polydactyly	DIS25BMZ	Strong	Biomarker	[7]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[23]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[24]
Rheumatoid arthritis	DISTSB4J	Strong	Biomarker	[25]
Small lymphocytic lymphoma	DIS30POX	Strong	Posttranslational Modification	[26]
Breast carcinoma	DIS2UE88	moderate	Biomarker	[8]
Clear cell renal carcinoma	DISBXRFJ	moderate	Biomarker	[27]
Colorectal carcinoma	DIS5PYL0	moderate	Biomarker	[28]
Endometrial cancer	DISW0LMR	moderate	Biomarker	[29]
Endometrial carcinoma	DISXR5CY	moderate	Biomarker	[29]
Kidney cancer	DISBIPKM	moderate	Altered Expression	[27]
leukaemia	DISS7D1V	moderate	Altered Expression	[30]
Leukemia	DISNAKFL	moderate	Altered Expression	[30]
Megalencephaly-capillary malformation-polymicrogyria syndrome	DISAHLVO	moderate	CausalMutation	[31]
Prostate cancer	DISF190Y	moderate	Altered Expression	[23]
Renal carcinoma	DISER9XT	moderate	Altered Expression	[27]
Renal cell carcinoma	DISQZ2X8	moderate	Biomarker	[27]
Megalencephaly-polymicrogyria-postaxial polydactyly-hydrocephalus syndrome	DISWVM8Y	Supportive	Autosomal dominant	[1]
Megalencephaly	DISYW5SV	Disputed	Genetic Variation	[6]
Hepatitis C virus infection	DISQ0M8R	Limited	Biomarker	[32]
Kaposi sarcoma	DISC1H1Z	Limited	Biomarker	[33]
Mesothelioma	DISKWK9M	Limited	Altered Expression	[34]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Phosphatidylinositol 3-kinase regulatory subunit beta (PIK3R2).	[35]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Phosphatidylinositol 3-kinase regulatory subunit beta (PIK3R2).	[47]

15 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Phosphatidylinositol 3-kinase regulatory subunit beta (PIK3R2).	[36]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Phosphatidylinositol 3-kinase regulatory subunit beta (PIK3R2).	[37]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Phosphatidylinositol 3-kinase regulatory subunit beta (PIK3R2).	[38]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Phosphatidylinositol 3-kinase regulatory subunit beta (PIK3R2).	[39]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Phosphatidylinositol 3-kinase regulatory subunit beta (PIK3R2).	[40]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Phosphatidylinositol 3-kinase regulatory subunit beta (PIK3R2).	[41]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Phosphatidylinositol 3-kinase regulatory subunit beta (PIK3R2).	[42]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of Phosphatidylinositol 3-kinase regulatory subunit beta (PIK3R2).	[43]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Phosphatidylinositol 3-kinase regulatory subunit beta (PIK3R2).	[44]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of Phosphatidylinositol 3-kinase regulatory subunit beta (PIK3R2).	[45]
Diclofenac	DMPIHLS	Approved	Diclofenac affects the expression of Phosphatidylinositol 3-kinase regulatory subunit beta (PIK3R2).	[44]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Phosphatidylinositol 3-kinase regulatory subunit beta (PIK3R2).	[39]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the expression of Phosphatidylinositol 3-kinase regulatory subunit beta (PIK3R2).	[46]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Phosphatidylinositol 3-kinase regulatory subunit beta (PIK3R2).	[48]
4-hydroxy-2-nonenal	DM2LJFZ	Investigative	4-hydroxy-2-nonenal decreases the expression of Phosphatidylinositol 3-kinase regulatory subunit beta (PIK3R2).	[43]

References

• [1] De novo germline and postzygotic mutations in AKT3, PIK3R2 and PIK3CA cause a spectrum of related megalencephaly syndromes. Nat Genet. 2012 Jun 24;44(8):934-40. doi: 10.1038/ng.2331.
• [2] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [3] Clinical and histopathologic evaluation of the expression of Ha-ras and fes oncogene products in lung cancer.Cancer. 1992 Mar 1;69(5):1130-6. doi: 10.1002/cncr.2820690512.
• [4] Yes and PI3K bind CD95 to signal invasion of glioblastoma.Cancer Cell. 2008 Mar;13(3):235-48. doi: 10.1016/j.ccr.2008.02.003.
• [5] Reduction of aluminum ion neurotoxicity through a small peptide application - NAP treatment of Alzheimer's disease.J Food Drug Anal. 2019 Apr;27(2):551-564. doi: 10.1016/j.jfda.2018.11.009. Epub 2019 Jan 12.
• [6] De novo PIK3R2 variant causes polymicrogyria, corpus callosum hyperplasia and focal cortical dysplasia.Eur J Hum Genet. 2016 Aug;24(9):1359-62. doi: 10.1038/ejhg.2016.7. Epub 2016 Feb 10.
• [7] Characterisation of mutations of the phosphoinositide-3-kinase regulatory subunit, PIK3R2, in perisylvian polymicrogyria: a next-generation sequencing study.Lancet Neurol. 2015 Dec;14(12):1182-95. doi: 10.1016/S1474-4422(15)00278-1. Epub 2015 Oct 29.
• [8] Candidate tumor suppressor gene IRF6 is involved in human breast cancer pathogenesis via modulating PI3K-regulatory subunit PIK3R2 expression.Cancer Manag Res. 2019 Jun 21;11:5557-5572. doi: 10.2147/CMAR.S203060. eCollection 2019.
• [9] Expression of a mutated form of the p85alpha regulatory subunit of phosphatidylinositol 3-kinase in a Hodgkin's lymphoma-derived cell line (CO).Leukemia. 2002 May;16(5):894-901. doi: 10.1038/sj.leu.2402484.
• [10] Inhibition of Growth and Metastasis of Colon Cancer by Delivering 5-Fluorouracil-loaded Pluronic P85 Copolymer Micelles.Sci Rep. 2016 Feb 11;6:20896. doi: 10.1038/srep20896.
• [11] Defective podocyte insulin signalling through p85-XBP1 promotes ATF6-dependent maladaptive ER-stress response in diabetic nephropathy.Nat Commun. 2015 Mar 10;6:6496. doi: 10.1038/ncomms7496.
• [12] MicroRNA-126 is down-regulated in human esophageal squamous cell carcinoma and inhibits the proliferation and migration in EC109 cell via PI3K/AKT signaling pathway.Int J Clin Exp Pathol. 2015 May 1;8(5):4745-54. eCollection 2015.
• [13] Phosphorylation of PI3K regulatory subunit p85 contributes to resistance against PI3K inhibitors in radioresistant head and neck cancer.Oral Oncol. 2018 Mar;78:56-63. doi: 10.1016/j.oraloncology.2018.01.014. Epub 2018 Feb 20.
• [14] MiR-126-3p suppresses tumor metastasis and angiogenesis of hepatocellular carcinoma by targeting LRP6 and PIK3R2.J Transl Med. 2014 Sep 22;12:259. doi: 10.1186/s12967-014-0259-1.
• [15] Tim-3 is a Marker of Plasmacytoid Dendritic Cell Dysfunction during HIV Infection and Is Associated with the Recruitment of IRF7 and p85 into Lysosomes and with the Submembrane Displacement of TLR9.J Immunol. 2017 Apr 15;198(8):3181-3194. doi: 10.4049/jimmunol.1601298. Epub 2017 Mar 6.
• [16] Targeted depletion of PIK3R2 induces regression of lung squamous cell carcinoma.Oncotarget. 2016 Dec 20;7(51):85063-85078. doi: 10.18632/oncotarget.13195.
• [17] Loss of merlin-p85 protein complex in NF2-related tumors.Int J Oncol. 1998 May;12(5):1073-8. doi: 10.3892/ijo.12.5.1073.
• [18] Abnormal G protein alpha(s) - and alpha(i2)-subunit mRNA expression in bipolar affective disorder.Mol Psychiatry. 1998 Nov;3(6):512-20. doi: 10.1038/sj.mp.4000393.
• [19] LZTS2 inhibits PI3K/AKT activation and radioresistance in nasopharyngeal carcinoma by interacting with p85.Cancer Lett. 2018 Apr 28;420:38-48. doi: 10.1016/j.canlet.2018.01.067. Epub 2018 Jan 31.
• [20] The p85 isoform of the kinase S6K1 functions as a secreted oncoprotein to facilitate cell migration and tumor growth.Sci Signal. 2018 Mar 27;11(523):eaao1052. doi: 10.1126/scisignal.aao1052.
• [21] MicroRNA-126 Targeting PIK3R2 Inhibits NSCLC A549 Cell Proliferation, Migration, and Invasion by Regulation of PTEN/PI3K/AKT Pathway.Clin Lung Cancer. 2016 Sep;17(5):e65-e75. doi: 10.1016/j.cllc.2016.03.012. Epub 2016 Apr 6.
• [22] A novel interaction between fibroblast growth factor receptor 3 and the p85 subunit of phosphoinositide 3-kinase: activation-dependent regulation of ERK by p85 in multiple myeloma cells.Hum Mol Genet. 2009 Jun 1;18(11):1951-61. doi: 10.1093/hmg/ddp116. Epub 2009 Mar 13.
• [23] LSD1 Activates PI3K/AKT Signaling Through Regulating p85 Expression in Prostate Cancer Cells.Front Oncol. 2019 Aug 2;9:721. doi: 10.3389/fonc.2019.00721. eCollection 2019.
• [24] The long tail of oncogenic drivers in prostate cancer.Nat Genet. 2018 May;50(5):645-651. doi: 10.1038/s41588-018-0078-z. Epub 2018 Apr 2.
• [25] Downregulated microRNA-135a ameliorates rheumatoid arthritis by inactivation of the phosphatidylinositol 3-kinase/AKT signaling pathway via phosphatidylinositol 3-kinase regulatory subunit 2.J Cell Physiol. 2019 Aug;234(10):17663-17676. doi: 10.1002/jcp.28390. Epub 2019 Mar 25.
• [26] Epigenetic silencing of tumor suppressor miR-3151 contributes to Chinese chronic lymphocytic leukemia by constitutive activation of MADD/ERK and PIK3R2/AKT signaling pathways.Oncotarget. 2015 Dec 29;6(42):44422-36. doi: 10.18632/oncotarget.6251.
• [27] Anticancer activity of Schiff base-Poloxamer P85 combination against kidney cancer.Int Urol Nephrol. 2018 Feb;50(2):247-255. doi: 10.1007/s11255-017-1782-9. Epub 2017 Dec 29.
• [28] DC-SIGN-LEF1/TCF1-miR-185 feedback loop promotes colorectal cancer invasion and metastasis.Cell Death Differ. 2020 Jan;27(1):379-395. doi: 10.1038/s41418-019-0361-2. Epub 2019 Jun 19.
• [29] New routes to old places: PIK3R1 and PIK3R2 join PIK3CA and PTEN as endometrial cancer genes.Cancer Discov. 2011 Jul;1(2):106-7. doi: 10.1158/2159-8290.CD-11-0116.
• [30] The regulation of tumor-suppressive microRNA, miR-126, inchronic lymphocytic leukemia.Cancer Med. 2017 Apr;6(4):778-787. doi: 10.1002/cam4.996. Epub 2017 Mar 15.
• [31] A combination of genetic and biochemical analyses for the diagnosis of PI3K-AKT-mTOR pathway-associated megalencephaly.BMC Med Genet. 2017 Jan 13;18(1):4. doi: 10.1186/s12881-016-0363-6.
• [32] Hepatitis C virus NS5A protein interacts with beta-catenin and stimulates its transcriptional activity in a phosphoinositide-3 kinase-dependent fashion.J Gen Virol. 2010 Feb;91(Pt 2):373-81. doi: 10.1099/vir.0.015305-0. Epub 2009 Oct 21.
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