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MicroRNA-141 Targets Sirt1 and Inhibits Autophagy to Reduce HBV Replication.
- Source :
-
Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology [Cell Physiol Biochem] 2017; Vol. 41 (1), pp. 310-322. Date of Electronic Publication: 2017 Jan 24. - Publication Year :
- 2017
-
Abstract
- Background/aims: About 400 million individuals are chronically infected with hepatitis B virus, at high risk of developing liver cirrhosis and hepatocellular carcinoma. Recent studies have demonstrated an interaction between hepatitis B virus replication and autophagy activity of hepatocytes. In the present study, we aimed to investigate the role of miR-141 in regulating autophagy and hepatitis B virus replication.<br />Methods: The expression of HBV-DNA, miR-141 and Sirt1 mRNA was determined by quantitative real-time PCR analysis. The expression of HBsAg and HBeAg was determined by ELISA. Western blotting was performed to detect protein expression. The LC3 puncta was determined by immunofluorescence. To test whether miR-141 directly regulate the expression level of Sirt1 mRNA, dual-luciferase reporter gene assay was performed.<br />Results: In vitro studies showed that miR-141 mimic inhibited the autophagic response, hepatitis B virus and the expression of Sirt1 in hepatocytes. And transfection with miR-141 inhibitor enhanced autophagic response and Sirt1 expression. The autophagy induced by overexpression of Sirt1 was inhibited by miR-141 mimic. In addition, miR-141 mimic also decreased the expression of Sirt1 mRNA. Sirt1 was predicted as a potential miR-141 target by bioinformatic analysis of its 3'-UTR, and confirmed by luciferase reporter assays which analyzing the interaction of miR-141 with the wild- type or the mutated Sirt1 3'-UTR.<br />Conclusion: We have therefore demonstrated a role of miR-141 in regulating autophagy-mediated hepatitis B virus inhibition by targeting Sirt1, and may provide potential targets for drug development.<br /> (© 2017 The Author(s) Published by S. Karger AG, Basel.)
- Subjects :
- 3' Untranslated Regions
Antagomirs metabolism
Base Sequence
Cell Line
DNA, Viral metabolism
Enzyme-Linked Immunosorbent Assay
Genes, Reporter
HeLa Cells
Hep G2 Cells
Hepatitis B Surface Antigens analysis
Hepatitis B e Antigens analysis
Hepatitis B virus genetics
Humans
MicroRNAs antagonists & inhibitors
MicroRNAs genetics
Microscopy, Fluorescence
RNA, Messenger metabolism
Sequence Alignment
Sirtuin 1 antagonists & inhibitors
Sirtuin 1 genetics
Virus Replication
Autophagy
Hepatitis B virus physiology
MicroRNAs metabolism
Sirtuin 1 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1421-9778
- Volume :
- 41
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 28135713
- Full Text :
- https://doi.org/10.1159/000456162