Effects of hepatitis C virus core protein and nonstructural protein 4B on the Wnt/β-catenin pathway

BMC Microbiology

Research Article

Ya-Ping Cai¹  Yu-Tao Xie²  Xiao-Hua Jiang³  Jing Ren³  Tao Ma³ 

[1] Department of Epidemiology and Health Statistics, the University of South China, 421001, Hengyang, China;Department of Infectious Diseases, Xiangya Hospital of Central South University, 410087, Changsha, China;Department of Infectious Diseases, the First Affiliated Hospital of the University of South China, 421001, Hengyang, China;

关键词: HCV;    Core protein;    NS4B;    Wnt/β-catenin signaling pathway;   

DOI  :  10.1186/s12866-017-1032-4

 received in 2017-01-13, accepted in 2017-05-15,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundHepatitis C virus (HCV) core protein and nonstructural protein 4B (NS4B) are potentially oncogenic. Aberrant activation of the Wnt/β-catenin signaling pathway is closely associated with hepatocarcinogenesis. We investigated the effects of HCV type 1b core protein and NS4B on Wnt/β-catenin signaling in various liver cells, and explored the molecular mechanism underlying HCV-related hepatocarcinogenesis.ResultsCompared with the empty vector control, HCV core protein and NS4B demonstrated the following characteristics in the Huh7 cells: significantly enhanced β-catenin/Tcf-dependent transcriptional activity (F = 40.87, P < 0.01); increased nuclear translocation of β-catenin (F = 165.26, P < 0.01); upregulated nuclear β-catenin, cytoplasmic β-catenin, Wnt1, c-myc, and cyclin D1 protein expression (P < 0.01); and promoted proliferation of Huh7 cells (P < 0.01 or P < 0.05). Neither protein enhanced β-catenin/Tcf-dependent transcriptional activity in the LO2 cells (F = 0.65, P > 0.05), but they did significantly enhance Wnt3a-induced β-catenin/Tcf-dependent transcriptional activity (F = 64.25, P < 0.01), and promoted the nuclear translocation of β-catenin (F = 66.54, P < 0.01) and the Wnt3a-induced proliferation of LO2 cells (P < 0.01 or P < 0.05). Moreover, activation of the Wnt/β-catenin signaling pathway was greater with the core protein than with NS4B (P < 0.01 or P < 0.05).ConclusionsHCV core protein and NS4B directly activate the Wnt/β-catenin signaling pathway in Huh7 cells and LO2 cells induced by Wnt3a. These data suggest that HCV core protein and NS4B contribute to HCV-associated hepatocellular carcinogenesis.

【 授权许可】

CC BY   
© The Author(s). 2017