PMID- 28545480 OWN - NLM STAT- MEDLINE DCOM- 20180102 LR - 20181113 IS - 1471-2180 (Electronic) IS - 1471-2180 (Linking) VI - 17 IP - 1 DP - 2017 May 25 TI - Effects of hepatitis C virus core protein and nonstructural protein 4B on the Wnt/beta-catenin pathway. PG - 124 LID - 10.1186/s12866-017-1032-4 [doi] LID - 124 AB - BACKGROUND: Hepatitis C virus (HCV) core protein and nonstructural protein 4B (NS4B) are potentially oncogenic. Aberrant activation of the Wnt/beta-catenin signaling pathway is closely associated with hepatocarcinogenesis. We investigated the effects of HCV type 1b core protein and NS4B on Wnt/beta-catenin signaling in various liver cells, and explored the molecular mechanism underlying HCV-related hepatocarcinogenesis. RESULTS: Compared with the empty vector control, HCV core protein and NS4B demonstrated the following characteristics in the Huh7 cells: significantly enhanced beta-catenin/Tcf-dependent transcriptional activity (F = 40.87, P < 0.01); increased nuclear translocation of beta-catenin (F = 165.26, P < 0.01); upregulated nuclear beta-catenin, cytoplasmic beta-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 beta-catenin/Tcf-dependent transcriptional activity in the LO2 cells (F = 0.65, P > 0.05), but they did significantly enhance Wnt3a-induced beta-catenin/Tcf-dependent transcriptional activity (F = 64.25, P < 0.01), and promoted the nuclear translocation of beta-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/beta-catenin signaling pathway was greater with the core protein than with NS4B (P < 0.01 or P < 0.05). CONCLUSIONS: HCV core protein and NS4B directly activate the Wnt/beta-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. FAU - Jiang, Xiao-Hua AU - Jiang XH AD - Department of Infectious Diseases, the First Affiliated Hospital of the University of South China, Hengyang, 421001, China. FAU - Xie, Yu-Tao AU - Xie YT AUID- ORCID: 0000-0003-1634-2059 AD - Department of Infectious Diseases, Xiangya Hospital of Central South University, Changsha, 410087, China. yutaoxiedoc@126.com. FAU - Cai, Ya-Ping AU - Cai YP AD - Department of Epidemiology and Health Statistics, the University of South China, Hengyang, 421001, China. FAU - Ren, Jing AU - Ren J AD - Department of Infectious Diseases, the First Affiliated Hospital of the University of South China, Hengyang, 421001, China. FAU - Ma, Tao AU - Ma T AD - Department of Infectious Diseases, the First Affiliated Hospital of the University of South China, Hengyang, 421001, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20170525 PL - England TA - BMC Microbiol JT - BMC microbiology JID - 100966981 RN - 0 (CCND1 protein, human) RN - 0 (CTNNB1 protein, human) RN - 0 (NS4B protein, flavivirus) RN - 0 (Viral Core Proteins) RN - 0 (Viral Nonstructural Proteins) RN - 0 (beta Catenin) RN - 0 (nucleocapsid protein, Hepatitis C virus) RN - 136601-57-5 (Cyclin D1) SB - IM MH - Animals MH - Cell Cycle/drug effects MH - Cell Line, Tumor MH - Cell Proliferation MH - Cyclin D1/metabolism MH - Hepatitis C/*metabolism MH - Humans MH - Mice MH - Signal Transduction/drug effects MH - Transcription, Genetic MH - Viral Core Proteins/*pharmacology MH - Viral Nonstructural Proteins/*pharmacology MH - Wnt Signaling Pathway/*drug effects MH - beta Catenin/*drug effects/metabolism PMC - PMC5445264 OTO - NOTNLM OT - Core protein OT - HCV OT - NS4B OT - Wnt/beta-catenin signaling pathway EDAT- 2017/05/27 06:00 MHDA- 2018/01/03 06:00 PMCR- 2017/05/25 CRDT- 2017/05/27 06:00 PHST- 2017/01/13 00:00 [received] PHST- 2017/05/15 00:00 [accepted] PHST- 2017/05/27 06:00 [entrez] PHST- 2017/05/27 06:00 [pubmed] PHST- 2018/01/03 06:00 [medline] PHST- 2017/05/25 00:00 [pmc-release] AID - 10.1186/s12866-017-1032-4 [pii] AID - 1032 [pii] AID - 10.1186/s12866-017-1032-4 [doi] PST - epublish SO - BMC Microbiol. 2017 May 25;17(1):124. doi: 10.1186/s12866-017-1032-4.