Rpn10 promotes tumor progression by regulating hypoxia-inducible factor 1 alpha through the PTEN/Akt signaling pathway in hepatocellular carcinoma.
The ubiquitin-proteasome pathway plays a pivotal role in tumor progression. Rpn10 is the major ubiquitin (Ub) receptor of the 26S proteasome. Mounting evidence shows that Rpn10 is associated with the progression of several tumor types. However, little is known regarding the mechanistic role of Rpn10 in hepatocellular carcinoma (HCC). In ... this study, we found that the upregulation of Rpn10 in HCC was associated with poor prognosis. The ectopic overexpression of Rpn10 increased HCC cell proliferation, whereas silencing Rpn10 expression resulted in decreased cell proliferation. Furthermore, we demonstrated that knockdown of Rpn10 induced cell cycle arrest at G1 phase in HCC cells. In addition, we found that Rpn10 increased cell proliferation via regulation of the PTEN/Akt pathways. Knockdown of Rpn10 induced suppression of cell proliferation could be reversed by overexpressing active Akt in HCC cells. Rpn10 directly promoted PTEN degradation through the ubiquitin-proteasome system. The transcription factor HIF1? directly bound to the Rpn10 promoter and increased its expression in HCC tissue. Moreover, we observed a significant correlation between HIF1? expression and Rpn10 levels in HCC patients and found that the combination of these two parameters was a more powerful predictor of poor prognosis than either parameter alone. Collectively, these findings highlight the molecular mechanism of Rpn10 expression in HCC and provide valuable information for cancer prognosis and treatment.
Mesh Terms:
Carcinoma, Hepatocellular, Cell Cycle Checkpoints, Cell Line, Cell Line, Tumor, Cell Proliferation, Disease Progression, G1 Phase, Gene Expression Regulation, Neoplastic, HEK293 Cells, Humans, Hypoxia-Inducible Factor 1, alpha Subunit, Liver Neoplasms, PTEN Phosphohydrolase, Prognosis, Proteasome Endopeptidase Complex, Proto-Oncogene Proteins c-akt, Signal Transduction, Up-Regulation
Carcinoma, Hepatocellular, Cell Cycle Checkpoints, Cell Line, Cell Line, Tumor, Cell Proliferation, Disease Progression, G1 Phase, Gene Expression Regulation, Neoplastic, HEK293 Cells, Humans, Hypoxia-Inducible Factor 1, alpha Subunit, Liver Neoplasms, PTEN Phosphohydrolase, Prognosis, Proteasome Endopeptidase Complex, Proto-Oncogene Proteins c-akt, Signal Transduction, Up-Regulation
Cancer Lett.
Date: Dec. 10, 2018
PubMed ID: 30673593
View in: Pubmed Google Scholar
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