ArticleCancer medicine2023
PIK3R3 is upregulated in liver cancer and activates Akt signaling to control cancer growth by regulation of CDKN1C and SMC1A.
Article in Cancer medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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17 citing papers in PubMed, 19 citations in OpenAlex.
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- Dietary polyphenols and hepatocellular carcinoma: protective mechanisms, challenges, and future directions.Discover oncology · 2026Review
- Structural maintenance of chromosome protein 1A exacerbates liver fibrosis by enhancing hepatic stellate cell activation and extracellular matrix synthesis via laminin subunit gamma 2 activation.Journal of cell communication and signaling · 2026Article
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- Systematic pan-cancer analysis identifies PIK3R3 as a lipid metabolism and immune regulation prognostic biomarker.Open medicine (Warsaw, Poland) · 2026Article
- Association of Structural Maintenance of Chromosome-1A Phosphorylation with Progression of Breast Cancer.Cells · 2025Article
- FTO Facilitates Cervical Cancer Malignancy Through Inducing m6A-Demethylation of PIK3R3 mRNA.Cancer medicine · 2024Article
- Liver cancer wars: plant-derived polyphenols strike back.Medical oncology (Northwood, London, England) · 2024Review
- CIP/KIP and INK4 families as hostages of oncogenic signaling.Cell division · 2024Review
- Establishment and characterization of cytochrome P450 1A1 CRISPR/Cas9 Knockout Bovine Foetal Hepatocyte Cell Line (BFH12).Cell biology and toxicology · 2024Article
- Prognostic model based on centrosome-related genes constructed in head and neck squamous cell carcinoma.Journal of Cancer · 2024Article
- Circ_0021350 plays an oncogene role by regulating miR-1207-3p/PIK3R3 in glioblastoma.BMC cancer · 2023Article
- Study the inhibitory effect and mechanism of the ethanol extract of deziyangxin on LLC cells.Heliyon · 2023Article
- PIK3R3 is upregulated in liver cancer and activates Akt signaling to control cancer growth by regulation of CDKN1C and SMC1A.Cancer medicine · 2023Article
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundLiver cancer is a highly malignant disease and the third leading cause of cancer death worldwide. Abnormal activation of PI3K/Akt signaling is common in cancer, but whether phosphoinositide-3-kinase regulatory subunit 3 (PIK3R3) plays a role in liver cancer is largely unexplored.
methodsWe determined the expression of PIK3R3 in liver cancer by using TCGA data and our clinical samples and knocked it down by siRNA or overexpressing it by the lentivirus vector system. We also investigated the function of PIK3R3 by colony formation, 5-Ethynyl-2-Deoxyuridine, flow cytometry assay, and subcutaneous xenograft model. The downstream of PIK3R3 was explored by RNA sequence and rescue assays.
resultsWe found that PIK3R3 was significantly upregulated in liver cancer and correlated with prognosis. PIK3R3 promoted liver cancer growth in vitro and in vivo by controlling cell proliferation and cell cycle. RNA sequence revealed that hundreds of genes were dysregulated upon PIK3R3 knockdown in liver cancer cells. CDKN1C, a cyclin-dependent kinase inhibitor, was significantly upregulated by PIK3R3 knockdown, and CDKN1C siRNA rescued the impaired tumor cell growth. SMC1A was partially responsible for PIK3R3 regulated function, and SMC1A overexpression rescued the impaired tumor cell growth in liver cancer cells. Immunoprecipitation demonstrated there is indirect interaction between PIK3R3 and CNKN1C or SMC1A. Importantly, we verified that PIK3R3-activated Akt signaling determined the expression of CDKN1C and SMC1A, two downstream of PIK3R3 in liver cancer cells.
conclusionPIK3R3 is upregulated in liver cancer and activates Akt signaling to control cancer growth by regulation of CDNK1C and SMC1A. Targeting PIK3R3 could be a promising treatment strategy for liver cancer that deserves further investigation.
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