HCV core protein-induced upregulation of microRNA-196a promotes aberrant proliferation in hepatocellular carcinoma by targeting FOXO1.
The hepatitis C virus (HCV) core protein is critical in the development of hepatocellular carcinoma (HCC). Investigations on HCC have previously focused on microRNAs, a class of small non‑coding RNAs, which are crucial in cancer development and progression. The present study aimed to investigate whether microRNA (miR)‑196a is aberrantly regulated by the HCV core protein, and whether miR‑196a is involved in the regulation of the aberrant proliferation of HCV‑HCC cells. In the study, miRNA expression was detected by quantitative polymerase chain reaction analysis. An Ad‑HCV core adenovirus was constructed and cell proliferation was measured using a Cell Counting Kit-8 assay and a cell cycle assay following infection. The results of the present study demonstrated that the HCV core protein increased the expression of miR‑196a, and that overexpression of miR‑196a in the HepG2 and Huh‑7 HCC cell lines promoted cell proliferation by inducing the G1‑S transition. Furthermore, the present study demonstrated that forkhead box O1 (FOXO1) was directly regulated by miR‑196a, and was essential in mediating the biological effects of miR‑196a in HCC. The overexpression of FOXO1 markedly reversed the effect of miR‑196a in HCC cell proliferation. Taken together, the data obtained in the present study provided compelling evidence that elevated expression levels of miR‑196a by the HCV core protein can function as an onco‑microRNA during HCV‑induced cell proliferation by downregulating the expression of FOXO1, indicating a potential novel therapeutic target for HCV-related HCC.
Department of Infectious Diseases, Changhai Hospital, Second Military Medical University, Shanghai 200433, P.R. China.
Hao
H
Xu
Department of Hepatology, The 6th People's Hospital of Zhengzhou, Zhengzhou, Henan 450000, P.R. China.
Guangming
G
Li
Department of Laboratory Diagnosis, Changhai Hospital, Second Military Medical University, Shanghai 200433, P.R. China.
Zhanyi
Z
Yue
Department of Infectious Diseases, Changhai Hospital, Second Military Medical University, Shanghai 200433, P.R. China.
Chengzhong
C
Li
D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D049109:Cell Proliferation; D000071161:Forkhead Box Protein O1 / Q000096:biosynthesis* / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D016174:Hepacivirus / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D012334:RNA, Neoplasm / Q000096:biosynthesis* / Q000235:genetics; D015854:Up-Regulation; D014758:Viral Core Proteins / Q000235:genetics / Q000378:metabolism*
C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; C542543:MIRN196 microRNA, human; D035683:MicroRNAs; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm; D014758:Viral Core Proteins; C069130:nucleocapsid protein, Hepatitis C virus