MiR-942 mediates hepatitis C virus-induced apoptosis via regulation of ISG12a

Darong Yang, Xianghe Meng, Binbin Xue, Nianli Liu, Xiaohong Wang, Haizhen Zhu

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

The interaction between hepatitis C virus (HCV) and human hepatic innate antiviral responses is unclear. The aim of this study was to examine how human hepatocytes respond to HCV infection. An infectious HCV isolate, JFH1, was used to infect a newly established human hepatoma cell line HLCZ01. Viral RNA or NS5A protein was examined by real-time PCR or immunofluorescence respectively. The mechanisms of HCV-induced IFN-βa and apoptosis were explored. Our data showed that HLCZ01 cells supported the entire HCV lifecycle and IFN-βa and interferon-stimulated genes (ISGs) were induced in HCVinfected cells. Viral infection caused apoptosis of HLCZ01 cells. Silencing of RIG-I, IRF3 or TRAIL inhibited ISG12a expression and blocked apoptosis of viral-infected HLCZ01 cells. Knockdown ISG12a blocked apoptosis of viral-infected cells. MiR-942 is a candidate negative regulator of ISG12a predicted by bioinformatics search. Moreover, HCV infection decreased miR-942 expression in HLCZ01 cells and miR-942 was inversely correlated with ISG12a expression in both HCV-infected cells and liver biopsies. MiR-942 forced expression in HLCZ01 cells decreased ISG12a expression and subsequently suppressed apoptosis triggered by HCV infection. Conversely, silencing of miR-942 expression by anti-miR-942 increased ISG12a expression and enhanced apoptosis in HCV-infected cells. Induction of Noxa by HCV infection contributed to ISG12a-mediated apoptosis. All the data indicated that innate host response is intact in HCV-infected hepatocytes. MiR-942 regulates HCV-induced apoptosis of human hepatocytes by targeting ISG12a. Our study provides a novel mechanism by which human hepatocytes respond to HCV infection.

Original languageEnglish (US)
Article numbere94501
JournalPloS one
Volume9
Issue number4
DOIs
StatePublished - Apr 11 2014

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Hepatitis C virus
Viruses
Hepacivirus
apoptosis
Apoptosis
Virus Diseases
hepatocytes
Hepatocytes
cells
infection
Hepatovirus
Noxae
hepatitis A
liver
Biopsy
Liver
Viral RNA
interferons
hepatoma
Bioinformatics

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

MiR-942 mediates hepatitis C virus-induced apoptosis via regulation of ISG12a. / Yang, Darong; Meng, Xianghe; Xue, Binbin; Liu, Nianli; Wang, Xiaohong; Zhu, Haizhen.

In: PloS one, Vol. 9, No. 4, e94501, 11.04.2014.

Research output: Contribution to journalArticle

Yang, Darong ; Meng, Xianghe ; Xue, Binbin ; Liu, Nianli ; Wang, Xiaohong ; Zhu, Haizhen. / MiR-942 mediates hepatitis C virus-induced apoptosis via regulation of ISG12a. In: PloS one. 2014 ; Vol. 9, No. 4.
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abstract = "The interaction between hepatitis C virus (HCV) and human hepatic innate antiviral responses is unclear. The aim of this study was to examine how human hepatocytes respond to HCV infection. An infectious HCV isolate, JFH1, was used to infect a newly established human hepatoma cell line HLCZ01. Viral RNA or NS5A protein was examined by real-time PCR or immunofluorescence respectively. The mechanisms of HCV-induced IFN-βa and apoptosis were explored. Our data showed that HLCZ01 cells supported the entire HCV lifecycle and IFN-βa and interferon-stimulated genes (ISGs) were induced in HCVinfected cells. Viral infection caused apoptosis of HLCZ01 cells. Silencing of RIG-I, IRF3 or TRAIL inhibited ISG12a expression and blocked apoptosis of viral-infected HLCZ01 cells. Knockdown ISG12a blocked apoptosis of viral-infected cells. MiR-942 is a candidate negative regulator of ISG12a predicted by bioinformatics search. Moreover, HCV infection decreased miR-942 expression in HLCZ01 cells and miR-942 was inversely correlated with ISG12a expression in both HCV-infected cells and liver biopsies. MiR-942 forced expression in HLCZ01 cells decreased ISG12a expression and subsequently suppressed apoptosis triggered by HCV infection. Conversely, silencing of miR-942 expression by anti-miR-942 increased ISG12a expression and enhanced apoptosis in HCV-infected cells. Induction of Noxa by HCV infection contributed to ISG12a-mediated apoptosis. All the data indicated that innate host response is intact in HCV-infected hepatocytes. MiR-942 regulates HCV-induced apoptosis of human hepatocytes by targeting ISG12a. Our study provides a novel mechanism by which human hepatocytes respond to HCV infection.",
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