AbstractMicroRNAs (miRNAs) play important roles in the posttranscriptional regulation of gene expression. Recent evidence has indicated the pathological relevance of miRNA dyregulation in hepatitis virus infection, however the roles of microRNAs in the regulation of hepatitis B virus (HBV) expression are still largely unknown. In this study, we have identified that miR-373 was upregulated in HBV-infected liver tissues and that the members of the miRs-371-372-373 (miRs-371-3) gene cluster were also significantly co-upregulated in HBV-producing HepG2.2.15 cells. A positive in vivo association was identified between hepatic HBV DNA levels and the copy number variation of the miRs-371-3 gene cluster. The enhanced expression of miRs-372/373 stimulated the production of HBV proteins and HBV core-associated DNA in HepG2 cells transfected with 1.3×HBV. Further, nuclear factor I/B (NFIB) was identified to be a direct functional target of miRs-372/373 by in silico algorithms and this was subsequently was confirmed by western blotting and luciferase reporter assays. Knockdown of NFIB by siRNA promoted HBV expression, whereas rescue of NFIB attenuated the stimulation in the 1.3×HBV transfected HepG2 cells. Conclusion: Our study revealed that the miRNA (miRs-372/373) can promote HBV expression through a pathway involving the transcription factor (NFIB). This novel model provides new insights into the molecular basis in HBV and host interaction. (HEPATOLOGY 2011.)
发表于 2011-6-4 12:45
