Статья

Mir-21 Suppression Promotes Mouse Hepatocarcinogenesis

Marta Correia de SousaDepartment of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, 1211 Geneva, SwitzerlandNicolas CaloDepartment of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, 1211 Geneva, SwitzerlandCyril SobolewskiDepartment of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, 1211 Geneva, SwitzerlandMonika GjorgjievaDepartment of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, 1211 Geneva, SwitzerlandSophie ClémentDivision of Clinical Pathology, Geneva University Hospitals, 1206 Geneva, SwitzerlandChristine MaederDepartment of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, 1211 Geneva, SwitzerlandDobrochna DolickaDepartment of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, 1211 Geneva, SwitzerlandMargot FournierDepartment of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, 1211 Geneva, SwitzerlandLaurent VinetDepartment of Radiology, Faculty of Medicine, University of Geneva, 1206 Geneva, SwitzerlandXavier MontetDepartment of Radiology, Faculty of Medicine, University of Geneva, 1206 Geneva, SwitzerlandJean‐François DufourDepartment for Visceral Surgery and Medicine, University Hospital Bern, 3010 Bern, SwitzerlandBostjan HumarDepartment of Visceral & Transplantation Surgery, University Hospital Zürich, 8006 Zürich, SwitzerlandFrancesco NegroDivision of Clinical Pathology, Geneva University Hospitals, 1206 Geneva, SwitzerlandChristine SempouxService of Clinical Pathology, University Institute of Pathology, Vaud University Hospital Center, 1011 Lausanne, SwitzerlandMichelangelo FotiDepartment of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland

2021en

ABI

Аннотация

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.

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Идентификаторы

DOI: 10.3390/cancers13194983

Цитирования и источники

Цитирований: 2Использованных источников: 0

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