Jiang Xiao-Hua, Xie Yu-Tao, Cai Ya-Ping, Ren Jing, Ma Tao
Department of Infectious Diseases, the First Affiliated Hospital of the University of South China, Hengyang, 421001, China.
Department of Infectious Diseases, Xiangya Hospital of Central South University, Changsha, 410087, China.
BMC Microbiol. 2017 May 25;17(1):124. doi: 10.1186/s12866-017-1032-4.
Hepatitis 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.
Compared 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).
HCV 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.
丙型肝炎病毒（HCV）核心蛋白和非结构蛋白4B（NS4B）具有潜在致癌性。Wnt/β-连环蛋白信号通路的异常激活与肝癌发生密切相关。我们研究了1b型HCV核心蛋白和NS4B对各种肝细胞中Wnt/β-连环蛋白信号的影响，并探讨了HCV相关肝癌发生的分子机制。
与空载体对照相比，HCV核心蛋白和NS4B在Huh7细胞中表现出以下特征：显著增强β-连环蛋白/Tcf依赖性转录活性（F = 40.87，P < 0.01）；增加β-连环蛋白的核转位（F = 165.26，P < 0.01）；上调核β-连环蛋白、胞质β-连环蛋白、Wnt1、c-myc和细胞周期蛋白D1蛋白表达（P < 0.01）；促进Huh7细胞增殖（P < 0.01或P < 0.05）。两种蛋白均未增强LO2细胞中β-连环蛋白/Tcf依赖性转录活性（F = 0.65，P > 0.05），但它们确实显著增强了Wnt3a诱导的β-连环蛋白/Tcf依赖性转录活性（F = 64.25，P < 0.01），并促进了β-连环蛋白的核转位（F = 66.54，P < 0.01）以及Wnt3a诱导的LO2细胞增殖（P < 0.01或P < 0.05）。此外，核心蛋白对Wnt/β-连环蛋白信号通路的激活作用大于NS4B（P < 0.01或P < 0.05）。
HCV核心蛋白和NS4B在Huh7细胞以及Wnt3a诱导的LO2细胞中直接激活Wnt/β-连环蛋白信号通路。这些数据表明HCV核心蛋白和NS4B参与了HCV相关的肝细胞癌发生。
