Correia de Sousa, Marta; Calo, Nicolas; Sobolewski, Cyril; Gjorgjieva, Monika; Clément, Sophie; Maeder, Christine; Dolicka, Dobrochna; Fournier, Margot; Vinet, Laurent; Montet, Xavier; Dufour, Jean-François; Humar, Bostjan; Negro, Francesco; Sempoux, Christine; Foti, Michelangelo (2021). Mir-21 Suppression Promotes Mouse Hepatocarcinogenesis. Cancers, 13(19) MDPI AG 10.3390/cancers13194983
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The microRNA 21 (miR-21) is upregulated in almost all known human cancers and is considered a highly potent oncogene and potential therapeutic target for cancer treatment. In the liver, miR-21 was reported to promote hepatic steatosis and inflammation, but whether miR-21 also drives hepatocarcinogenesis remains poorly investigated in vivo. Here we show using both carcinogen (Diethylnitrosamine, DEN) or genetically (PTEN deficiency)-induced mouse models of hepatocellular carcinoma (HCC), total or hepatocyte-specific genetic deletion of this microRNA fosters HCC development-contrasting the expected oncogenic role of miR-21. Gene and protein expression analyses of mouse liver tissues further indicate that total or hepatocyte-specific miR-21 deficiency is associated with an increased expression of oncogenes such as Cdc25a, subtle deregulations of the MAPK, HiPPO, and STAT3 signaling pathways, as well as alterations of the inflammatory/immune anti-tumoral responses in the liver. Together, our data show that miR-21 deficiency promotes a pro-tumoral microenvironment, which over time fosters HCC development via pleiotropic and complex mechanisms. These results question the current dogma of miR-21 being a potent oncomiR in the liver and call for cautiousness when considering miR-21 inhibition for therapeutic purposes in HCC.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Hepatology |
UniBE Contributor: |
Dufour, Jean-François |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
2072-6694 |
Publisher: |
MDPI AG |
Language: |
English |
Submitter: |
Rahel Fuhrer |
Date Deposited: |
26 Oct 2021 18:07 |
Last Modified: |
05 Dec 2022 15:53 |
Publisher DOI: |
10.3390/cancers13194983 |
PubMed ID: |
34638467 |
Uncontrolled Keywords: |
HCC PTEN fibrosis immune cells inflammation microRNA 21 oncogenes tumor suppressors |
BORIS DOI: |
10.48350/160182 |
URI: |
https://boris.unibe.ch/id/eprint/160182 |
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