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Downregulation of Peptidylprolyl isomerase A promotes cell death and enhances doxorubicin-induced apoptosis in hepatocellular carcinoma.
- Source :
-
Gene [Gene] 2016 Oct 10; Vol. 591 (1), pp. 236-244. Date of Electronic Publication: 2016 Jul 08. - Publication Year :
- 2016
-
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.<br /> (Copyright © 2016 Elsevier B.V. All rights reserved.)
- 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
Subjects
Details
- Language :
- English
- ISSN :
- 1879-0038
- Volume :
- 591
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Gene
- Publication Type :
- Academic Journal
- Accession number :
- 27397650
- Full Text :
- https://doi.org/10.1016/j.gene.2016.07.020