title: Downregulation of Peptidylprolyl isomerase A promotes cell death and enhances doxorubicin-induced apoptosis in hepatocellular carcinoma.
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.
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Key Laboratory of Organ Transplantation, Zhejiang Province, Hangzhou 310003, China.
authors.forename: Shaobing
authors.initials: S
authors.lastname: Cheng
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
authors.forename: Mengchao
authors.initials: M
authors.lastname: Luo
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
authors.forename: Chaofeng
authors.initials: C
authors.lastname: Ding
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
authors.forename: Chuanhui
authors.initials: C
authors.lastname: Peng
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Lv
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
authors.forename: Rongliang
authors.initials: R
authors.lastname: Tong
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
authors.forename: Heng
authors.initials: H
authors.lastname: Xiao
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
authors.forename: Haiyang
authors.initials: H
authors.lastname: Xie
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China. Electronic address: drwujian@hotmail.com.
authors.forename: Jian
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Key Laboratory of Organ Transplantation, Zhejiang Province, Hangzhou 310003, China. Electronic address: shusenzheng@zju.edu.cn.
authors.forename: Shusen
authors.initials: S
authors.lastname: Zheng
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D006528:Carcinoma, Hepatocellular / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D053179:Caspase 7 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects*; D004317:Doxorubicin / Q000494:pharmacology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D055785:Gene Knockdown Techniques; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D019696:Peptidylprolyl Isomerase / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D014162:Transfection; D051020:bcl-X Protein / Q000378:metabolism
chemical_list: D034741:RNA, Small Interfering; D051020:bcl-X Protein; D004317:Doxorubicin; D053179:Caspase 7; D019696:Peptidylprolyl Isomerase
keywords: Apoptosis; Cell growth; Doxorubicin; Hepatocellular carcinoma; Peptidylprolyl isomerase A