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October 4, 2021
- doi: 10.3390/cancers13194983
- issn: 2072-6694
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info:eu-repo/semantics/altIdentifier/doi/10.3390/cancers13194983
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info:eu-repo/semantics/altIdentifier/pmid/34638467
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info:eu-repo/semantics/altIdentifier/pissn/2072-6694
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info:eu-repo/semantics/altIdentifier/urn/urn:nbn:ch:serval-BIB_A5895BE9610F2
info:eu-repo/semantics/openAccess , CC BY 4.0 , https://creativecommons.org/licenses/by/4.0/
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Mouse House mice Mus musculus House mouseCite this document
M. Correia de Sousa et al., « Mir-21 Suppression Promotes Mouse Hepatocarcinogenesis. », Serveur académique Lausannois, ID : 10.3390/cancers13194983
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Abstract
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.
