title: Upregulation of PP2Ac predicts poor prognosis and contributes to aggressiveness in hepatocellular carcinoma.
abstract: Protein phosphatase 2A (PP2A) is a heterotrimeric protein phosphatase consisting of a 36-kD catalytic C subunit (PP2Ac). This study aimed to explore the prognostic and biological significance of PP2Ac in human hepatocellular carcinoma (HCC). High PP2Ac expression was significantly (P < 0.01) associated with serum hepatitis B surface antigen positivity, serum hepatitis B e antigen positivity, liver cirrhosis, moderate to poor differentiation grade, advanced disease stage, intrahepatic metastasis, and early recurrence in HCC. Multivariate analysis revealed PP2Ac as an independent prognostic factor for overall survival. Enforced expression of hepatitis B virus X protein (HBx) and its carboxyl-terminal truncated isoform induced PP2Ac expression in HCC cells. Co-immunoprecipitation assay revealed a direct interaction between PP2Ac and HBx. Small interfering RNA-mediated knockdown of PP2Ac significantly inhibited in vitro cell proliferation, colony formation, migration, and invasion and reduced tumor growth in an xenograft mouse model. In contrast, overexpression of PP2Ac promoted HCC cell proliferation, colony formation, and tumorigenesis. Additionally, silencing of PP2Ac impaired the growth-promoting effects on HepG2 HCC cells elicited by overexpression of carboxyl-terminal truncated HBx. Gene expression profiling analysis showed that PP2Ac downregulation modulated the expression of numerous genes involved in cell cycle and apoptosis regulation. Collectively, PP2Ac upregulation has a poor prognostic impact on the overall survival of HCC patients and contributes to the aggressiveness of HCC. PP2Ac may represent a potential therapeutic target for HCC.
authors.affiliation: a Department of Interventional oncology , Renji Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai , China.
authors.forename: Shao-Juan
authors.initials: SJ
authors.lastname: Gong
authors.affiliation: b Department of Pathology , Yueyang Hospital, Shanghai University of Traditional Chinese Medicine , Shanghai , China.
authors.forename: Xiao-Jun
authors.initials: XJ
authors.lastname: Feng
authors.affiliation: a Department of Interventional oncology , Renji Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai , China.
authors.forename: Wei-Hua
authors.initials: WH
authors.lastname: Song
authors.affiliation: a Department of Interventional oncology , Renji Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai , China.
authors.forename: Jian-Ming
authors.initials: JM
authors.lastname: Chen
authors.affiliation: b Department of Pathology , Yueyang Hospital, Shanghai University of Traditional Chinese Medicine , Shanghai , China.
authors.forename: Shou-Mei
authors.initials: SM
authors.lastname: Wang
authors.affiliation: a Department of Interventional oncology , Renji Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai , China.
authors.forename: Dong-Juan
authors.initials: DJ
authors.lastname: Xing
authors.affiliation: c Department of Pathology , Changhai Hospital and Institute of Liver Diseases, Second Military Medical University , Shanghai , China.
authors.forename: Ming-Hua
authors.initials: MH
authors.lastname: Zhu
authors.affiliation: b Department of Pathology , Yueyang Hospital, Shanghai University of Traditional Chinese Medicine , Shanghai , China.
authors.forename: Shu-Hui
authors.initials: SH
authors.lastname: Zhang
authors.affiliation: a Department of Interventional oncology , Renji Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai , China.
authors.forename: Ai-Min
authors.initials: AM
authors.lastname: Xu
mesh_terms: D000368:Aged; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000235:genetics* / Q000473:pathology / Q000821:virology; D002453:Cell Cycle / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006514:Hepatitis B Surface Antigens / Q000097:blood / Q000235:genetics; D006515:Hepatitis B virus / Q000235:genetics / Q000472:pathogenicity; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000097:blood / Q000235:genetics* / Q000473:pathology / Q000821:virology; D008297:Male; D051379:Mice; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics; D011379:Prognosis; D054648:Protein Phosphatase 2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000097:blood / Q000235:genetics*; D015534:Trans-Activators / Q000096:biosynthesis* / Q000097:blood; D054334:Viral Regulatory and Accessory Proteins
chemical_list: D006514:Hepatitis B Surface Antigens; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein; D054648:Protein Phosphatase 2
keywords: Growth; hepatitis B virus X protein; hepatocellular carcinoma; invasiveness; prognosis; protein phosphatase 2A