1. Downregulation of Peptidylprolyl isomerase A promotes cell death and enhances doxorubicin-induced apoptosis in hepatocellular carcinoma.
- Author
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Cheng S, Luo M, Ding C, Peng C, Lv Z, Tong R, Xiao H, Xie H, Zhou L, Wu J, and Zheng S
- Subjects
- Carcinoma, Hepatocellular genetics, Caspase 7 metabolism, Cell Line, Tumor, Cell Proliferation drug effects, Female, Gene Expression Regulation, Neoplastic drug effects, Gene Knockdown Techniques, Humans, Liver Neoplasms enzymology, Liver Neoplasms genetics, Male, Middle Aged, Peptidylprolyl Isomerase blood, Peptidylprolyl Isomerase metabolism, RNA, Small Interfering metabolism, Transfection, bcl-X Protein metabolism, Apoptosis drug effects, Carcinoma, Hepatocellular enzymology, Carcinoma, Hepatocellular pathology, Down-Regulation drug effects, Doxorubicin pharmacology, Liver Neoplasms pathology, Peptidylprolyl Isomerase genetics
- Abstract
Peptidylprolyl isomerase A (PPIA) is a peptidyl-prolyl cis-trans isomerase that is known to play a critical role in the development of many human cancers. However, the precise biological function of PPIA in hepatocellular carcinoma (HCC) remains largely unclear. In this study, lentiviral overexpression vectors and small interfering RNA knockdown methods were employed to investigate the biological effects of PPIA in HCC. PPIA levels in HCC tissues and peritumoral tissues were detected by real-time Polymerase Chain Reaction (RT-PCR), Western blotting, and immunohistochemistry. Our results indicate that PPIA levels were significantly higher in the HCC tissues compared to the matched peritumoral tissues. Moreover, PPIA expression was significantly associated with tumor size in these tissues. Interestingly, serum PPIA (sPPIA) levels were significantly higher in healthy controls compared to the HCC patients. Knockdown or overexpression of PPIA was shown to downregulate and upregulate cell growth, respectively. Moreover, PPIA siRNA knockdown appears to promote doxorubicin-induced apoptosis in HCC cells, altering the expression of downstream apoptotic factors. In summary, our results indicate that PPIA may play a pivotal role in HCC by regulating cell growth and could serve as a novel marker and therapeutic molecular target for HCC patients., (Copyright © 2016 Elsevier B.V. All rights reserved.)
- Published
- 2016
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