Affinage

PIK3R3

Phosphatidylinositol 3-kinase regulatory subunit gamma · UniProt Q92569

Length
461 aa
Mass
54.4 kDa
Annotated
2026-06-10
68 papers in source corpus 21 papers cited in narrative 21 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PIK3R3 (p55γ), a class IA PI3K regulatory subunit, functions as a pro-proliferative, pro-survival node that drives cell cycle progression and tumor cell invasion across multiple tissues by activating PI3K/AKT and ERK signaling (PMID:22876838, PMID:29682174). Loss of PIK3R3 promotes apoptosis and imposes G0/G1 arrest with reduced Rb phosphorylation, cyclin D1, and PCNA, while restoring p21/CDKN1C and CDK4 inhibition (PMID:17875760, PMID:22876838, PMID:39466763). Beyond its kinase-adaptor role, PIK3R3 acts in the nucleus by physically binding p53 and blocking its occupancy of the p21 promoter, thereby suppressing senescence (PMID:32973127), and it controls stem-cell differentiation and senescence through a FOXO1 axis (PMID:39862908). PIK3R3 drives epithelial-to-mesenchymal transition through context-specific effectors — SNAI2 in colorectal cancer and an ERK1/2–ZEB1 cascade in pancreatic cancer — and sustains stemness via a PIK3R3/ERK/Nanog axis in sarcoma (PMID:24837077, PMID:29719293, PMID:34321458). It forms a functional complex with the regulatory subunit PIK3R1 to jointly regulate PI3K/AKT/mTOR signaling (PMID:39183556). Its expression is multiply controlled: transcriptionally by NKX2.1 (repressed by TGF-β), FOXM1, and KMT2C-mediated H3K4 methylation (PMID:25371235, PMID:29682174, PMID:35870559), and post-transcriptionally by m6A dynamics in which VHL-orchestrated METTL3/METTL14 writing and FTO demethylation tune PIK3R3 mRNA stability (PMID:38618953, PMID:39692250). Outside cancer, PIK3R3 governs hepatic lipid metabolism through an HNF4α–PPARα axis and intestinal barrier integrity via NF-κB/ZO-1 (PMID:29350678, PMID:32473571).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2007 Medium

    Established that PIK3R3 is required for cancer cell survival, defining its first cellular phenotype as a pro-survival regulatory subunit.

    Evidence siRNA knockdown with apoptosis readout in ovarian cancer cell lines

    PMID:17875760

    Open questions at the time
    • No molecular mechanism linking PIK3R3 loss to apoptosis
    • Single cancer type, single method
  2. 2012 Medium

    Connected PIK3R3 to cell cycle machinery, showing it promotes G1/S progression rather than acting solely on survival.

    Evidence siRNA knockdown with FACS cell cycle analysis and Western blot for Rb/cyclin D1/PCNA in gastric cancer cells

    PMID:22876838

    Open questions at the time
    • Does not establish whether the effect requires PI3K catalytic activity
    • Upstream regulators unidentified
  3. 2014 Medium

    Defined PIK3R3 as a driver of EMT and metastasis and placed it within the TGF-β/NKX2.1 transcriptional circuit, identifying both a downstream effector (SNAI2) and an upstream control.

    Evidence OE/KD with migration/invasion and in vivo metastasis assays (colorectal); promoter-binding and rescue assays (lung adenocarcinoma)

    PMID:24837077 PMID:25371235

    Open questions at the time
    • Direct mechanistic link from PIK3R3 to SNAI2 not resolved
    • Tissue-specific effectors not generalized
  4. 2018 Medium

    Extended PIK3R3 control of EMT/proliferation to multiple effectors (ERK1/2-ZEB1, NF-κB/TP) and identified transcriptional activators FOXM1, broadening its signaling reach beyond canonical AKT.

    Evidence ChIP, OE/KD, in vitro and in vivo assays across esophageal, pancreatic, and colorectal cancers

    PMID:29370570 PMID:29682174 PMID:29719293

    Open questions at the time
    • Whether ERK and AKT branches are independent or convergent is unresolved
    • FOXM1 binding shown but functional specificity for PIK3R3 not isolated
  5. 2018 Medium

    Demonstrated a non-oncogenic physiological role, placing PIK3R3 in hepatic lipid handling via an HNF4α-PPARα axis using in vivo gain- and loss-of-function.

    Evidence Liver-specific knockout and overexpression mouse models with metabolic phenotyping

    PMID:29350678

    Open questions at the time
    • Mechanism by which PIK3R3 induces HNF4α/PPARα is undefined
    • Relationship to canonical PI3K signaling unclear
  6. 2019 Medium

    Showed PIK3R3 abundance is post-transcriptionally tuned by non-coding RNA, linking 3'UTR-targeting miRNA machinery to AKT/NF-κB-driven malignancy.

    Evidence 3'UTR binding assay, RIP-seq, functional assays, in vivo metastasis in cervical cancer

    PMID:31474757

    Open questions at the time
    • GRSF1-dependent upregulation mechanism not fully resolved
    • Generality of miR-G-10 unknown
  7. 2020 Medium

    Revealed a moonlighting nuclear function: PIK3R3 binds p53 and blocks p21 promoter occupancy to suppress senescence, decoupling part of its activity from kinase-adaptor signaling.

    Evidence Co-IP, promoter occupancy assay, OE/KD with senescence markers in colorectal cancer

    PMID:32973127

    Open questions at the time
    • Structural basis of PIK3R3-p53 binding unknown
    • Reciprocal validation and direct binding interface not mapped
  8. 2020 Medium

    Established PIK3R3 control of epithelial barrier integrity through NF-κB/ZO-1 and validated it as a therapeutic target with a peptide inhibitor in colitis.

    Evidence OE/KD in Caco-2, TEER, immunofluorescence, in vivo DSS colitis with TAT-N15 inhibitor

    PMID:32473571

    Open questions at the time
    • Direct vs indirect NF-κB activation by PIK3R3 not separated
    • Off-target effects of TAT-N15 not excluded
  9. 2021 Medium

    Connected PIK3R3 to cancer stem-cell phenotypes through a PIK3R3/ERK/Nanog axis, implicating it in stemness and chemoresistance.

    Evidence shRNA, inhibitors, spheroid/CSC assays, xenograft in sarcoma

    PMID:34321458

    Open questions at the time
    • How PIK3R3 selectively engages ERK vs AKT in CSCs is unclear
    • Direct regulation of Nanog not shown
  10. 2022 Medium

    Identified epigenetic transcriptional control of PIK3R3 by KMT2C-deposited H3K4 methylation, linking chromatin state to PIK3R3/AKT/NF-κB-driven inflammation.

    Evidence ChIP for H3K4me3/me1, KMT2C knockdown, in vivo psoriasis mouse model

    PMID:35870559

    Open questions at the time
    • Whether KMT2C acts directly or via intermediate factors is not resolved
    • Generality beyond keratinocytes unknown
  11. 2023 Medium

    Refined the proliferative mechanism, showing PIK3R3 represses CDKN1C and supports SMC1A to sustain liver cancer growth, with rescue confirming causality.

    Evidence siRNA/OE, RNA-seq, IP, rescue assays, xenograft

    PMID:37212524

    Open questions at the time
    • Interactions reported as indirect; direct effectors unmapped
    • Link to canonical PI3K activity not dissected
  12. 2024 Medium

    Established m6A as a major layer of PIK3R3 regulation, with VHL-orchestrated METTL3/METTL14 writing stabilizing the transcript and FTO demethylation modulating it, and revealed a tumor-suppressive arm in which PIK3R3 promotes p85 ubiquitination to restrain PI3K/AKT.

    Evidence MeRIP-seq, writer-complex assembly assays, p85 ubiquitination assay, FTO OE/KD rescue in ccRCC and cervical cancer

    PMID:38618953 PMID:39692250

    Open questions at the time
    • Reconciliation of PIK3R3 oncogenic vs tumor-suppressive roles by context not resolved
    • Direct vs indirect role in p85 ubiquitination unclear
  13. 2024 Medium

    Demonstrated PIK3R3 forms a physical complex with PIK3R1 and that both are co-targeted by miR-29 cluster suppression, establishing a cooperative regulatory-subunit module in PI3K/AKT/mTOR signaling.

    Evidence Co-IP (PIK3R1-PIK3R3), luciferase 3'UTR assay, rescue, in vivo metastasis in gastric cancer

    PMID:39183556

    Open questions at the time
    • Stoichiometry and functional consequence of the PIK3R1-PIK3R3 complex undefined
    • Whether they co-regulate the same catalytic subunit unknown
  14. 2025 Medium

    Extended PIK3R3 control of senescence to non-malignant stem cells through a FOXO1 axis, with epistasis confirming FOXO1 acts downstream.

    Evidence shRNA/OE, differentiation and senescence assays, FOXO1 siRNA rescue, in vivo aged rat model

    PMID:39862908

    Open questions at the time
    • Mechanism by which PIK3R3 modulates FOXO1 expression not defined
    • Relationship to the p53/p21 senescence pathway unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • How PIK3R3 switches between oncogenic PI3K/AKT activation and tumor-suppressive p85 ubiquitination, and how its kinase-adaptor versus nuclear p53-binding functions are partitioned, remains unresolved.
  • No structural model of PIK3R3 in complex with p110, PIK3R1, or p53
  • Context determinants of opposing PIK3R3 functions not defined
  • Direct enzymatic activity in p85 ubiquitination not established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 3 GO:0140110 transcription regulator activity 1
Localization
GO:0005634 nucleus 1
Pathway
R-HSA-74160 Gene expression (Transcription) 3 R-HSA-162582 Signal Transduction 2 R-HSA-1640170 Cell Cycle 2 R-HSA-8953897 Cellular responses to stimuli 2 R-HSA-1430728 Metabolism 1
Partners
LACTBPIK3R1TP53
Complex memberships
PI3K class IA regulatory complex (with PIK3R1)

Evidence

Reading pass · 21 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2007 PIK3R3 knockdown by siRNA significantly increased apoptosis in ovarian cancer cell lines, demonstrating a pro-survival role for the p55γ regulatory subunit in ovarian cancer cells. siRNA knockdown with apoptosis readout in cultured ovarian cancer cell lines Clinical cancer research Medium 17875760
2012 PIK3R3 knockdown in gastric cancer cells induced G0/G1 cell cycle arrest and decreased retinoblastoma protein (Rb) phosphorylation, cyclin D1, and PCNA expression, establishing PIK3R3 as a promoter of cell cycle progression. siRNA knockdown, FACS cell cycle analysis, crystal violet/BrdU proliferation assays, Western blot BMC medical genomics Medium 22876838
2014 PIK3R3 overexpression induces epithelial-to-mesenchymal transition (EMT) dependent on SNAI2 expression, and its downregulation reverses EMT in colorectal cancer cells, promoting invasion and metastasis in vitro and in vivo. Overexpression and knockdown with in vitro migration/invasion assays and in vivo metastasis model, Western blot for EMT markers Molecular cancer therapeutics Medium 24837077
2014 TGF-β downregulates PIK3R3 expression by attenuating the transcriptional activity of NKX2.1, a transcription factor that binds the PIK3R3 promoter; PIK3R3 overexpression attenuates TGF-β-induced inhibition of lung adenocarcinoma cell proliferation, placing PIK3R3 downstream of the TGF-β/NKX2.1 axis. Promoter-binding studies, overexpression rescue assay, Western blot, cell proliferation assays, correlation in clinical samples Molecular carcinogenesis Medium 25371235
2018 FOXM1 directly binds the PIK3R3 promoter (confirmed by chromatin immunoprecipitation) and regulates its expression; FOXM1 overexpression activates PI3K/AKT signaling through PIK3R3-mediated AKT phosphorylation in esophageal squamous cell carcinoma cells. Chromatin immunoprecipitation (ChIP), transcriptome analysis, overexpression experiments, Western blot for AKT phosphorylation Oncotarget Medium 29682174
2018 PIK3R3 overexpression promotes hepatic fatty acid β-oxidation by inducing PPARα expression in a HNF4α-dependent manner; hepatic PIK3R3 knockout increases hepatic triglyceride levels, and overexpression improves the fatty liver phenotype in high-fat diet mice, defining a novel PIK3R3-HNF4α-PPARα signaling axis in lipid metabolism. Overexpression and liver-specific knockout mouse models, gene expression analysis, phenotypic assessment of hepatosteatosis Experimental & molecular medicine Medium 29350678
2018 PIK3R3 promotes pancreatic cancer cell migration and invasion through the ERK1/2-ZEB1 pathway, triggering epithelial-mesenchymal transition; PIK3R3 overexpression or knockdown respectively promotes or suppresses metastasis in vitro and in vivo. RNAi knockdown, overexpression, in vitro migration/invasion assays, in vivo metastasis model, Western blot for ERK1/2-ZEB1 and EMT markers Cellular physiology and biochemistry Medium 29719293
2018 PIK3R3 promotes chemotherapeutic sensitivity of colorectal cancer cells to 5-FU by enhancing 5-FU-induced apoptosis through upregulation of thymidine phosphorylase (TP) via the PIK3R3/NF-κB/TP pathway. Overexpression/knockdown, apoptosis assay, Western blot, clinical database analysis Cancer biology & therapy Low 29370570
2019 A novel miRNA (miR-G-10) bound to the 3' UTR of PIK3R3 mRNA and upregulated its expression in a GRSF1-dependent manner, activating the AKT/NF-κB signaling pathway to promote cervical cancer cell migration, invasion, and anoikis resistance. 3' UTR binding assay, RIP-seq, overexpression, in vitro functional assays (migration/invasion/anoikis), in vivo lung metastasis model Cell death & disease Medium 31474757
2020 PIK3R3 physically binds p53 and inhibits p53 binding to the p21 gene promoter region, thereby suppressing p21 transcriptional activity and inhibiting cellular senescence of colorectal cancer cells. Co-immunoprecipitation (binding of PIK3R3 to p53), promoter binding assay (ChIP or reporter assay for p53-p21 interaction), overexpression/knockdown with senescence markers Cell death & disease Medium 32973127
2020 PIK3R3 overexpression activates the NF-κB pathway to downregulate ZO-1 expression, thereby disrupting epithelial tight junction integrity and increasing intestinal permeability; inhibition of PIK3R3 with TAT-N15 ameliorated DSS-induced intestinal permeability in mice. Overexpression and siRNA knockdown in Caco-2 cells, TEER measurement, immunoblot and immunofluorescence for tight junction proteins, in vivo DSS colitis model with PIK3R3 inhibitor International immunopharmacology Medium 32473571
2020 LACTB regulates PIK3R3 activity (confirmed by immunoprecipitation) to influence PI3K/AKT/mTOR pathway activation; LACTB overexpression inhibits EMT and proliferation and promotes autophagy in colorectal cancer cells partly through PIK3R3. Immunoprecipitation, Western blot, RNA-seq, transwell/MTT assays, xenograft model Cancer management and research Low 32636680
2021 PIK3R3 activates both AKT and ERK signaling in sarcoma cancer stem-like cells; inhibition of PIK3R3 using shRNA reduced Nanog expression, spheroid formation, anchorage-independent growth, migration, invasion, MMP-2 secretion, and chemotherapy resistance, defining a PIK3R3/ERK/Nanog axis in sarcoma CSC phenotypes. shRNA knockdown, pharmacological inhibitors, spheroid/CSC assays, Western blot for AKT/ERK/Nanog, xenograft invasion assay, chemotherapy resistance assay Cell death & disease Medium 34321458
2022 KMT2C promotes PIK3R3 transcription by regulating histone H3K4me3 enrichment at the PIK3R3 promoter and H3K4me1 at the enhancer; the resulting PIK3R3/AKT/NF-κB signaling drives keratinocyte hyperproliferation and cytokine secretion in psoriasiform inflammation. ChIP for histone marks at PIK3R3 promoter/enhancer, KMT2C knockdown with phenotypic and downstream signaling readouts, in vivo mouse psoriasis model The Journal of investigative dermatology Medium 35870559
2023 PIK3R3 activates AKT signaling to control liver cancer cell growth; PIK3R3 knockdown upregulates CDKN1C (a cyclin-dependent kinase inhibitor) and reduces SMC1A; immunoprecipitation demonstrated indirect interactions between PIK3R3 and CDKN1C or SMC1A, and rescue of CDKN1C or SMC1A reversed PIK3R3 knockdown-induced growth inhibition. siRNA and lentivirus overexpression, colony formation/EdU/flow cytometry assays, xenograft model, RNA sequencing, rescue assays, immunoprecipitation Cancer medicine Medium 37212524
2023 MCT4 overexpression promotes L929 fibroblast cell migration via activation of an IGF1/IGF1R/PIK3R3/SGK1 signaling axis; inhibition of IGF1R or SGK1 mitigated MCT4-promoted migration, placing PIK3R3 in this upstream signaling cascade. RNA sequencing, RT-qPCR, Western blot, wound healing assay, IGF1R/SGK1 inhibitor experiments Oncology letters Low 37745980
2024 VHL governs m6A modification of PIK3R3 mRNA by orchestrating assembly of m6A writer proteins METTL3 and METTL14, stabilizing PIK3R3 mRNA; PIK3R3 contributes to p85 ubiquitination, which restrains PI3K/AKT signaling and impedes clear cell renal cell carcinoma (ccRCC) growth. m6A transcriptome profiling (MeRIP-seq), METTL3/METTL14 complex assembly assays, p85 ubiquitination assay, cell and mouse models (referenced study reviewed in this paper) The Journal of clinical investigation Medium 38618953
2024 FTO demethylates m6A on PIK3R3 mRNA, decreasing its m6A level and affecting FoxO pathway activation; FTO knockdown increases PIK3R3 m6A modification (detected by MeRIP-seq/qPCR), and PIK3R3 upregulation restores cervical cancer cell malignancy reduced by FTO knockdown. MeRIP-seq and MeRIP-qPCR for m6A profiling, lentivirus-mediated FTO overexpression/knockdown, rescue assay with PIK3R3 overexpression, in vitro and in vivo functional assays Cancer medicine Medium 39692250
2024 POU2F1 binds the miR-29b1/a cluster promoter to suppress miR-29b-3p and miR-29a-3p expression; these miRNAs directly target PIK3R3 (and PIK3R1); PIK3R1 and PIK3R3 interact with each other (co-immunoprecipitation) and jointly regulate GC cell invasion/migration via PI3K/AKT/mTOR signaling. Co-immunoprecipitation (PIK3R1–PIK3R3 interaction), luciferase 3'-UTR assay, promoter analysis, rescue experiments, in vivo metastasis model, Western blot Chinese medical journal Medium 39183556
2024 ZSTK474 (a PI3K inhibitor) targets PIK3R3 to induce G0/G1 phase arrest in Wilms' tumor cells; PIK3R3 knockdown confirmed that ZSTK474 acts by downregulating PIK3R3, reducing AKT phosphorylation, cyclin D, and CDK4 levels and elevating p21 expression. PIK3R3 siRNA knockdown, CCK-8, flow cytometry cell cycle assay, Western blot for AKT phosphorylation/cyclin D/CDK4/p21, in vivo xenograft model PloS one Medium 39466763
2025 PIK3R3 regulates differentiation and senescence of human periodontal ligament stem cells (hPDLSCs) by modulating FOXO1 expression; PIK3R3 knockdown promotes senescence and inhibits multi-lineage differentiation, while PIK3R3 overexpression has opposite effects; FOXO1 knockdown promotes senescence and weakens the senescence-promoting effect of PIK3R3 knockdown, establishing PIK3R3–FOXO1 as a regulatory axis. shRNA knockdown and overexpression, osteogenic/adipogenic/chondrogenic differentiation assays, senescence markers, ROS and telomerase assays, FOXO1 siRNA rescue, in vivo aged rat alveolar bone loss model (micro-CT and histology) Journal of advanced research Medium 39862908

Source papers

Stage 0 corpus · 68 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2014 MicroRNA-193a-3p and -5p suppress the metastasis of human non-small-cell lung cancer by downregulating the ERBB4/PIK3R3/mTOR/S6K2 signaling pathway. Oncogene 229 24469061
2020 CircRNA_0000392 promotes colorectal cancer progression through the miR-193a-5p/PIK3R3/AKT axis. Journal of experimental & clinical cancer research : CR 107 33317596
2007 Integrative genomic analysis of phosphatidylinositol 3'-kinase family identifies PIK3R3 as a potential therapeutic target in epithelial ovarian cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 103 17875760
2019 HOXD-AS1 promotes the epithelial to mesenchymal transition of ovarian cancer cells by regulating miR-186-5p and PIK3R3. Journal of experimental & clinical cancer research : CR 88 30823895
2020 PIK3R3 regulates ZO-1 expression through the NF-kB pathway in inflammatory bowel disease. International immunopharmacology 72 32473571
2014 PIK3R3 induces epithelial-to-mesenchymal transition and promotes metastasis in colorectal cancer. Molecular cancer therapeutics 60 24837077
2016 HOTAIR Promotes Proliferation, Migration, and Invasion of Ovarian Cancer SKOV3 Cells Through Regulating PIK3R3. Medical science monitor : international medical journal of experimental and clinical research 58 26826873
2019 miR-224-5p inhibits proliferation, migration, and invasion by targeting PIK3R3/AKT3 in uveal melanoma. Journal of cellular biochemistry 57 30825222
2019 A novel miRNA identified in GRSF1 complex drives the metastasis via the PIK3R3/AKT/NF-κB and TIMP3/MMP9 pathways in cervical cancer cells. Cell death & disease 54 31474757
2015 MiR-132 inhibits cell proliferation, invasion and migration of hepatocellular carcinoma by targeting PIK3R3. International journal of oncology 54 26252738
2020 LACTB Regulates PIK3R3 to Promote Autophagy and Inhibit EMT and Proliferation Through the PI3K/AKT/mTOR Signaling Pathway in Colorectal Cancer. Cancer management and research 50 32636680
2020 PIK3R3 inhibits cell senescence through p53/p21 signaling. Cell death & disease 50 32973127
2020 LncRNA H19 Attenuates Apoptosis in MPTP-Induced Parkinson's Disease Through Regulating miR-585-3p/PIK3R3. Neurochemical research 49 32356199
2020 RETRACTED: Long non-coding RNA LINC00160 functions as a decoy of microRNA-132 to mediate autophagy and drug resistance in hepatocellular carcinoma via inhibition of PIK3R3. Cancer letters 47 32067991
2020 Inhibition of exosomal miR-24-3p in diabetes restores angiogenesis and facilitates wound repair via targeting PIK3R3. Journal of cellular and molecular medicine 47 33142041
2017 MicroRNA-365 inhibits proliferation, migration and invasion of glioma by targeting PIK3R3. Oncology reports 45 28260020
2016 miR-152 functions as a tumor suppressor in colorectal cancer by targeting PIK3R3. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 41 26820128
2021 Circular RNA hsa_circ_0061395 accelerates hepatocellular carcinoma progression via regulation of the miR-877-5p/PIK3R3 axis. Cancer cell international 40 33407443
2018 PIK3R3 regulates PPARα expression to stimulate fatty acid β-oxidation and decrease hepatosteatosis. Experimental & molecular medicine 39 29350678
2012 Genetic and bioinformatic analyses of the expression and function of PI3K regulatory subunit PIK3R3 in an Asian patient gastric cancer library. BMC medical genomics 39 22876838
2015 MiR-511 inhibits growth and metastasis of human hepatocellular carcinoma cells by targeting PIK3R3. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 35 25608840
2016 Genetic and Methylation-Induced Loss of miR-181a2/181b2 within chr9q33.3 Facilitates Tumor Growth of Cervical Cancer through the PIK3R3/Akt/FoxO Signaling Pathway. Clinical cancer research : an official journal of the American Association for Cancer Research 32 27503199
2018 Esophageal squamous cell carcinoma transcriptome reveals the effect of FOXM1 on patient outcome through novel PIK3R3 mediated activation of PI3K signaling pathway. Oncotarget 26 29682174
2018 Mir-1287 suppresses the proliferation, invasion, and migration in hepatocellular carcinoma by targeting PIK3R3. Journal of cellular biochemistry 26 29953647
2020 microRNA-1236 promotes chondrocyte apoptosis in osteoarthritis via direct suppression of PIK3R3. Life sciences 25 32325132
2018 miR‑1273g‑3p promotes proliferation, migration and invasion of LoVo cells via cannabinoid receptor 1 through activation of ERBB4/PIK3R3/mTOR/S6K2 signaling pathway. Molecular medicine reports 25 29328379
2015 Variable expression of PIK3R3 and PTEN in Ewing Sarcoma impacts oncogenic phenotypes. PloS one 23 25603314
2021 circ_PTN contributes to -cisplatin resistance in glioblastoma via PI3K/AKT signaling through the miR-542-3p/PIK3R3 pathway. Molecular therapy. Nucleic acids 22 34853725
2020 MiR-186 bidirectionally regulates cisplatin sensitivity of ovarian cancer cells via suppressing targets PIK3R3 and PTEN and upregulating APAF1 expression. Journal of Cancer 21 32284740
2023 PIK3R3 is upregulated in liver cancer and activates Akt signaling to control cancer growth by regulation of CDKN1C and SMC1A. Cancer medicine 20 37212524
2017 MicroRNA-411 inhibits malignant biological behaviours of colorectal cancer cells by directly targeting PIK3R3. Oncology reports 20 29207180
2022 KMT2C Induced by FABP5P3 Aggravates Keratinocyte Hyperproliferation and Psoriasiform Skin Inflammation by Upregulating the Transcription of PIK3R3. The Journal of investigative dermatology 19 35870559
2018 PIK3R3 promotes chemotherapeutic sensitivity of colorectal cancer through PIK3R3/NF-kB/TP pathway. Cancer biology & therapy 19 29370570
2018 PIK3R3 Promotes Metastasis of Pancreatic Cancer via ZEB1 Induced Epithelial-Mesenchymal Transition. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 18 29719293
2021 PIK3R3, part of the regulatory domain of PI3K, is upregulated in sarcoma stem-like cells and promotes invasion, migration, and chemotherapy resistance. Cell death & disease 17 34321458
2019 MicroRNA‑601 serves as a potential tumor suppressor in hepatocellular carcinoma by directly targeting PIK3R3. Molecular medicine reports 15 30664174
2018 Mechanism of miR-137 regulating migration and invasion of melanoma cells by targeting PIK3R3 gene. Journal of cellular biochemistry 15 30485524
2021 MiR-513b-5p represses autophagy during the malignant progression of hepatocellular carcinoma by targeting PIK3R3. Aging 13 34120890
2014 TGF-β regulates the proliferation of lung adenocarcinoma cells by inhibiting PIK3R3 expression. Molecular carcinogenesis 13 25371235
2022 PIK3R3, a regulatory subunit of PI3K, modulates ovarian cancer stem cells and ovarian cancer development and progression by integrative analysis. BMC cancer 11 35761259
2022 Curcumin suppresses colorectal cancer development with epithelial-mesenchymal transition via modulating circular RNA HN1/miR-302a-3p/PIK3R3 axis. Journal of physiology and pharmacology : an official journal of the Polish Physiological Society 11 35988930
2020 MicroRNA-367 directly targets PIK3R3 to inhibit proliferation and invasion of oral carcinoma cells. Bioscience reports 11 32378714
2024 VHL governs m6A modification and PIK3R3 mRNA stability in clear cell renal cell carcinomas. The Journal of clinical investigation 10 38618953
2024 POU2F1 inhibits miR-29b1/a cluster-mediated suppression of PIK3R1 and PIK3R3 expression to regulate gastric cancer cell invasion and migration. Chinese medical journal 9 39183556
2022 Regulation of circADAMTS6-miR-324-5p-PIK3R3 ceRNA pathway may be a novel mechanism of IL-1β-induced osteoarthritic chondrocytes. Journal of bone and mineral metabolism 9 35333985
2021 LncRNA JHDM1D-AS1 Suppresses MPP + -Induced Neuronal Injury in Parkinson's Disease via miR-134-5p/PIK3R3 Axis. Neurotoxicity research 9 34773593
2017 MicroRNA‑212 inhibits colorectal cancer cell viability and invasion by directly targeting PIK3R3. Molecular medicine reports 9 28944887
2017 [IL-6 promotes gastric cancer cell proliferation and EMT through regulating miR-152/PIK3R3 pathway]. Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences 9 29187649
2022 miR-27a Targeting PIK3R3 Regulates the Proliferation and Apoptosis of Sheep Hair Follicle Stem Cells. Animals : an open access journal from MDPI 8 36611750
2021 Circ_0045714/miR-331-3p interaction affects IL-1β-evoked human articular chondrocyte injury through regulating PIK3R3 in a ceRNA regulatory cascade. Journal of orthopaedic surgery and research 7 34649564
2021 Combination Therapy with PIK3R3-siRNA and EGFR-TKI Erlotinib Synergistically Suppresses Glioblastoma Cell Growth In Vitro. Asian Pacific journal of cancer prevention : APJCP 7 34967581
2024 Circ_0044235 regulates the development of osteoarthritis by the modulation of miR-375/PIK3R3 axis. Journal of orthopaedic surgery and research 6 38622668
2023 Circ_0021350 plays an oncogene role by regulating miR-1207-3p/PIK3R3 in glioblastoma. BMC cancer 5 37644421
2021 Sulforaphane suppresses autophagy during the malignant progression of gastric carcinoma via activating miR-4521/PIK3R3 pathway. Human & experimental toxicology 5 34749521
2025 PIK3R3 regulates differentiation and senescence of periodontal ligament stem cells and mitigates age-related alveolar bone loss by modulating FOXO1 expression. Journal of advanced research 4 39862908
2023 Traditional Chinese medicine Kuan-Sin-Yin decoction inhibits cell mobility via downregulation of CCL2, CEACAM1 and PIK3R3 in hepatocellular carcinoma cells. Journal of ethnopharmacology 4 37355084
2020 MicroRNA-29c-3p inhibits osteosarcoma cell proliferation through targeting PIK3R3. European review for medical and pharmacological sciences 4 32196574
2018 Investigating PIK3R3 and ATp2A1 Genes Expressions in Ventilator-Associated Pneumonia Patients Admitted to the Intensive Care Unit of Masih Daneshvari Hospital in 2016. Reports of biochemistry & molecular biology 4 29765993
2024 FTO Facilitates Cervical Cancer Malignancy Through Inducing m6A-Demethylation of PIK3R3 mRNA. Cancer medicine 3 39692250
2025 NONHSAT141192.2 Facilitates the Stemness and Radioresistance of Glioma Stem Cells via the Regulation of PIK3R3 and SOX2. CNS neuroscience & therapeutics 2 39968701
2024 ZSTK474 targeting PIK3R3 inhibits the Wilms' tumor through G0 / G1 phase arrest. PloS one 2 39466763
2023 PIK3R3 is a candidate regulator of platelet count in people of Bangladeshi ancestry. Research and practice in thrombosis and haemostasis 2 37538507
2024 Engineered CARD11-PIK3R3 T-cell therapies as weapons of cancer mass destruction. MedComm 1 38952574
2023 [Retracted] MicroRNA‑212 inhibits colorectal cancer cell viability and invasion by directly targeting PIK3R3. Molecular medicine reports 1 37264958
2023 Monocarboxylate transporter 4 promotes the migration of non‑cancerous L929 fibroblast cells by activating the IGF1/IGF1R/PIK3R3/SGK1 axis. Oncology letters 1 37745980
2022 [Retracted] MicroRNA‑601 serves as a potential tumor suppressor in hepatocellular carcinoma by directly targeting PIK3R3. Molecular medicine reports 1 36562346
2022 [Retracted] MicroRNA-411 inhibits malignant biological behaviours of colorectal cancer cells by directly targeting PIK3R3. Oncology reports 0 35169854
2021 [Retracted] MiR‑132 inhibits cell proliferation, invasion and migration of hepatocellular carcinoma by targeting PIK3R3. International journal of oncology 0 34195847

Missed literature

Know a paper Affinage missed for PIK3R3? Flag it for the maintainers and the community.

No submissions yet.