Voltage-gated sodium channels ?3 subunit promotes tumorigenesis in hepatocellular carcinoma by facilitating p53 degradation.
The voltage-gated sodium channels (VGSCs) are aberrantly expressed in a variety of tumors and play an important role in tumor growth and metastasis. Here, we show that VGSCs auxiliary ?3 subunit, encoded by the SCN3B gene, promotes proliferation and suppresses apoptosis in HepG2 cells by promoting p53 degradation. ?3 significantly ... increases HepG2 cell proliferation, promotes tumor growth in mouse xenograft models, and suppresses senescence and apoptosis. We found that ?3 knockdown stabilizes p53 protein, leading to potentiation of p53-induced cell cycle arrest, senescence, and apoptosis. Mechanistic studies revealed that ?3 could bind to p53, promoting p53 ubiquitination and degradation by stabilizing the p53/MDM2 complex. Our results suggest that ?3 is a novel negative regulator of p53 and a potential oncogenic factor.
Mesh Terms:
Carcinogenesis, Carcinoma, Hepatocellular, Cell Cycle, Cell Proliferation, Cellular Senescence, Gene Knockdown Techniques, Hep G2 Cells, Humans, Liver Neoplasms, Proteolysis, Proto-Oncogene Proteins c-mdm2, Tumor Suppressor Protein p53, Ubiquitination, Voltage-Gated Sodium Channel beta-3 Subunit
Carcinogenesis, Carcinoma, Hepatocellular, Cell Cycle, Cell Proliferation, Cellular Senescence, Gene Knockdown Techniques, Hep G2 Cells, Humans, Liver Neoplasms, Proteolysis, Proto-Oncogene Proteins c-mdm2, Tumor Suppressor Protein p53, Ubiquitination, Voltage-Gated Sodium Channel beta-3 Subunit
FEBS Lett
Date: Dec. 01, 2019
PubMed ID: 31626714
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