title: Proteomic identification of RhoA as a potential biomarker for proliferation and metastasis in hepatocellular carcinoma.
abstract: Hepatocellular carcinoma (HCC) is one of the most common malignancies in the world, and there is an urgent need to discover novel factors that can act as biomarkers for prognostic assessment and therapeutic targets of HCC. In this study, highly purified plasma membrane proteins from clinical tissue samples were obtained using a strategy combining sucrose density gradient centrifugation and subsequent phase partition. Using a two-dimensional gel electrophoresis and MALDI-Q-TOF MS/MS-based proteomics approach, we identified 13 plasma membrane-associated proteins that were differentially expressed in HCC and normal liver tissues. Of those, RhoA was one of the most significantly upregulated proteins in HCC, and its overexpression was confirmed using Western blotting. Immunohistochemistry suggested a link between RhoA expression and poor differentiation and clinicopathologic stage. Suppression of RhoA expression in HepG2 and Hep3B cells by RNA interference led to significant inhibition of cell growth, induction of apoptosis, and a decrease in migration. Our data suggest that RhoA may serve as a potential biomarker and an attractive therapeutic target for HCC.
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, People's Republic of China. goulantu@gmail.com
authors.forename: Lantu
authors.initials: L
authors.lastname: Gou
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Aiping
authors.initials: A
authors.lastname: Tong
authors.forename: Yuqin
authors.initials: Y
authors.lastname: Yao
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhou
authors.forename: Cheng
authors.initials: C
authors.lastname: Yi
authors.forename: Jinliang
authors.initials: J
authors.lastname: Yang
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology*; D002454:Cell Differentiation; D002462:Cell Membrane / Q000378:metabolism; D002465:Cell Movement; D049109:Cell Proliferation; D002499:Centrifugation, Density Gradient; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008875:Middle Aged; D009362:Neoplasm Metastasis; D040901:Proteomics / Q000379:methods*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D008565:Membrane Proteins; D020742:rhoA GTP-Binding Protein