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      Essential metabolic, anti-inflammatory, and anti-tumorigenic functions of miR-122 in liver.

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          Abstract

          miR-122, an abundant liver-specific microRNA (miRNA), regulates cholesterol metabolism and promotes hepatitis C virus (HCV) replication. Reduced miR-122 expression in hepatocellular carcinoma (HCC) correlates with metastasis and poor prognosis. Nevertheless, the consequences of sustained loss of function of miR-122 in vivo have not been determined. Here, we demonstrate that deletion of mouse Mir122 resulted in hepatosteatosis, hepatitis, and the development of tumors resembling HCC. These pathologic manifestations were associated with hyperactivity of oncogenic pathways and hepatic infiltration of inflammatory cells that produce pro-tumorigenic cytokines, including IL-6 and TNF. Moreover, delivery of miR-122 to a MYC-driven mouse model of HCC strongly inhibited tumorigenesis, further supporting the tumor suppressor activity of this miRNA. These findings reveal critical functions for miR-122 in the maintenance of liver homeostasis and have important therapeutic implications, including the potential utility of miR-122 delivery for selected patients with HCC and the need for careful monitoring of patients receiving miR-122 inhibition therapy for HCV.

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          Author and article information

          Journal
          J Clin Invest
          The Journal of clinical investigation
          American Society for Clinical Investigation
          1558-8238
          0021-9738
          Aug 2012
          : 122
          : 8
          Affiliations
          [1 ] Molecular, Cellular, and Developmental Biology Program, The Ohio State University, Columbus, OH, USA.
          Article
          63539
          10.1172/JCI63539
          3408748
          22820288
          9c3944e2-fdaf-46d4-98ec-429a0e7b2a7c
          History

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