MicroRNA-122 supports robust innate immunity in hepatocytes by targeting the RTKs/STAT3 signaling pathway
- Sun Yat-sen University, China
- Cited 0
- Views 1,060
- Annotations
Abstract
MicroRNA-122 (miR-122) is the most abundant microRNA in hepatocytes and a central player in liver biology and disease. Herein, we report a previously unknown role for miR-122 in hepatocyte intrinsic innate immunity. Restoring miR-122 levels in hepatoma cells markedly enhanced the activation of interferons (IFNs) in response to a variety of viral nucleic acids or simulations, especially of hepatitis C virus RNA and poly (I:C). Mechanistically, miR-122 down-regulated the phosphorylation (Tyr705) of STAT3 and thereby removed the negative regulation of STAT3 on IFN-signaling. While STAT3 represses IFN expression by inhibiting interferon regulatory factor 1 (IRF1), miR-122 targets MERTK, FGFR1 and IGF1R, three receptor tyrosine kinases (RTKs) that directly promote STAT3 phosphorylation. This work identifies a miR-122-RTKs/STAT3-IRF1-IFNs regulatory circuitry, which may play a pivotal role in regulating hepatocyte innate immunity. These findings renewed our knowledge about miR-122's function and have important implications for treating hepatitis viruses.
Article and author information
Author details
Funding
National Natural Science Foundation of China (31200593)
- Hui Xu
National Natural Science Foundation of China (31230042)
- Liang-Hu Qu
National Natural Science Foundation of China (31471223)
- Liang-Hu Qu
National Natural Science Foundation of China (31671349)
- Liang-Hu Qu
Natural Science Foundation of Guangdong Province (2014A030313163)
- Hui Xu
National Basic Research Program of China (2011CB811300)
- Liang-Hu Qu
National Key R&D Program of China (2017YFA0504400)
- Jian-Hua Yang
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Stephen P Goff, Howard Hughes Medical Institute, Columbia University, United States
Publication history
- Received: August 16, 2018
- Accepted: February 7, 2019
- Accepted Manuscript published: February 8, 2019 (version 1)
- Version of Record published: February 25, 2019 (version 2)
Copyright
© 2019, Xu et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 1,060
- Page views
-
- 212
- Downloads
-
- 0
- Citations
Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.
Download links
Downloads (link to download the article as PDF)
Download citations (links to download the citations from this article in formats compatible with various reference manager tools)
Open citations (links to open the citations from this article in various online reference manager services)
Further reading
-
- Immunology and Inflammation
- Microbiology and Infectious Disease
-
- Biochemistry and Chemical Biology
- Immunology and Inflammation
