MiR-3613-3p impairs IFN-induced immune response by targeting CMPK1 in chronic hepatitis B
Yanping Zhao1, Yaping Yu1, Lei Ye1
1First Affiliated Hospital of Zhejiang University of Traditional Chinese Medicine, Hangzhou 310005, Zhejiang, China.
Background:
This study aims to investigate the effects of miR-3613-3p and its underlying mechanisms on chronic hepatitis B.
Methods:
Expressions of miR-3613-3p were determined in clinical samples from chronic hepatitis B patients and healthy volunteers. HBV-transfected hepatoma cell lines were constructed for in vitro study. HBV-infected animal model was established in vivo study. Quantitative real-time reverse transcription PCR (qRT-PCR) was used to determine mRNA expressions. Western blotting and ELISA were used to determine protein expressions. Luciferase reporter and biotin pull-down assays were used to analyze RNA-RNA interactions. siRNA silencing was used to knockdown miR-3613-3p and CMPK1.
Results:
MiR-3613-3p was upregulated in the chronic hepatitis B patients, as compared with healthy volunteers. Inhibition of miR-3613-3p decreased relative expressions of IFN-α and IFN-β, HBV DNA copies, and increased the hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) levels, whereas miR-3613-3p overexpression reversed these changes in vitro and in vivo. MiR-3613-3p directly targeted CMPK1 and interactions between CMPK1 and miR-3613-3p regulated the anti-HBV efficiency of IFN.
Conclusion:
MiR-3613-3p impaired IFN-induced immune response by targeting CMPK1 in chronic hepatitis B.
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