Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 117, Issue 1, Pages 454-463Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1909145117
Keywords
microRNAs; fibrosis; hepatocellular carcinoma; PPAR gamma
Categories
Funding
- International Max Planck Research School (University Tubingen)
- Deutsche Konsortium fur Translationale Krebsforschung (DKTK) Joint Funding Consortium Noncoding mutations in cancer genomes
- Deutsche Forschungsgemeinschaft (DFG [German Research Foundation]) [314905040 -TRR 209]
- German Cancer Aid [109886]
- Deutsches Bundesministerium fur Bildung und Forschung (BMBF) [031L0045]
- DFG [SFB/TRR 57]
- Interdisciplinary Center for Clinical Research within the Faculty of Medicine at the Rheinisch-Westfalische Technische Hochschule (RWTH) Aachen [O3-1]
Ask authors/readers for more resources
Liver fibrosis interferes with normal liver function and facilitates hepatocellular carcinoma (HCC) development, representing a major threat to human health. Here, we present a comprehensive perspective of microRNA (miRNA) function on targeting the fibrotic microenvironment. Starting from a murine HCC model, we identify a miRNA network composed of 8 miRNA hubs and 54 target genes. We show that let-7, miR-30, miR-29c, miR-335, and miR-338 (collectively termed antifibrotic microRNAs [AF-miRNAs]) down-regulate key structural, signaling, and remodeling components of the extracellular matrix. During fibrogenic transition, these miRNAs are transcriptionally regulated by the transcription factor Ppar gamma and thus we identify a role of Ppar gamma as regulator of a functionally related class of AF-miRNAs. The miRNA network is active in human HCC, breast, and lung carcinomas, as well as in 2 independent mouse liver fibrosis models. Therefore, we identify a miRNA:mRNA network that contributes to formation of fibrosis in tumorous and nontumorous organs of mice and humans.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available