| RRC ID |
59961
|
| 著者 |
Jiang Z, Zhou Q, Ge C, Yang J, Li H, Chen T, Xie H, Cui Y, Shao M, Li J, Tian H.
|
| タイトル |
Rpn10 promotes tumor progression by regulating hypoxia-inducible factor 1 alpha through the PTEN/Akt signaling pathway in hepatocellular carcinoma.
|
| ジャーナル |
Cancer Lett
|
| Abstract |
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 HIF1α directly bound to the Rpn10 promoter and increased its expression in HCC tissue. Moreover, we observed a significant correlation between HIF1α 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.
|
| 巻・号 |
447
|
| ページ |
1-11
|
| 公開日 |
2019-4-10
|
| DOI |
10.1016/j.canlet.2019.01.020
|
| PII |
S0304-3835(19)30032-1
|
| PMID |
30673593
|
| MeSH |
Carcinoma, Hepatocellular / genetics*
Carcinoma, Hepatocellular / pathology
Cell Cycle Checkpoints / genetics
Cell Line
Cell Line, Tumor
Cell Proliferation / genetics
Disease Progression
G1 Phase / genetics
Gene Expression Regulation, Neoplastic / genetics
HEK293 Cells
Humans
Hypoxia-Inducible Factor 1, alpha Subunit / genetics*
Liver Neoplasms / genetics*
Liver Neoplasms / pathology
PTEN Phosphohydrolase / genetics*
Prognosis
Proteasome Endopeptidase Complex / genetics*
Proto-Oncogene Proteins c-akt / genetics*
RNA-Binding Proteins
Signal Transduction / genetics*
Up-Regulation / genetics
|
| IF |
6.508
|
| 引用数 |
5
|
| リソース情報 |
| ヒト・動物細胞 |
Huh-7 |
