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Essential metabolic, anti-inflammatory, and anti-tumorigenic functions of miR-122 in liver.
- Source :
-
The Journal of clinical investigation [J Clin Invest] 2012 Aug; Vol. 122 (8), pp. 2871-83. Date of Electronic Publication: 2012 Jul 23. - Publication Year :
- 2012
-
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.
- Subjects :
- 3' Untranslated Regions
Animals
Base Sequence
Carcinoma, Hepatocellular genetics
Carcinoma, Hepatocellular metabolism
Carcinoma, Hepatocellular therapy
Cell Proliferation
Cell Survival genetics
Cytokines biosynthesis
Fatty Liver etiology
Fatty Liver genetics
Fatty Liver metabolism
Fatty Liver pathology
Gene Expression
Genes, Tumor Suppressor
Genes, myc
Humans
Lipid Metabolism genetics
Lipids blood
Liver immunology
Liver metabolism
Liver pathology
Liver Neoplasms genetics
Liver Neoplasms metabolism
Liver Neoplasms therapy
Liver Neoplasms, Experimental etiology
Mice
Mice, 129 Strain
Mice, Knockout
MicroRNAs antagonists & inhibitors
MicroRNAs therapeutic use
Monocytes immunology
Monocytes pathology
Neutrophils immunology
Neutrophils pathology
RNA, Neoplasm genetics
RNA, Neoplasm metabolism
Liver Neoplasms, Experimental genetics
Liver Neoplasms, Experimental metabolism
MicroRNAs genetics
MicroRNAs metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1558-8238
- Volume :
- 122
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- The Journal of clinical investigation
- Publication Type :
- Academic Journal
- Accession number :
- 22820288
- Full Text :
- https://doi.org/10.1172/JCI63539