Reciprocal Regulation between SIRT6 and miR-122 Controls Liver Metabolism and Predicts Hepatocarcinoma Prognosis
| Autor: | Batia Lerrer, Rotem Ben-Hamo, Renana Glazz, Yariv Kanfi, Sivan Elhanati, Alexander Varvak, Sol Efroni, Haim Y. Cohen |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Untranslated region SIRT6 Carcinoma Hepatocellular Biology General Biochemistry Genetics and Molecular Biology Mice 03 medical and health sciences microRNA MiR-122 medicine Animals Humans Sirtuins lcsh:QH301-705.5 Beta oxidation fatty acid oxidation Fatty Acids Liver Neoplasms Prognosis medicine.disease Phenotype miR-122 MicroRNAs 030104 developmental biology Liver lcsh:Biology (General) Hepatocellular carcinoma Cancer research Biomarker (medicine) Oxidation-Reduction |
| Zdroj: | Cell Reports, Vol 14, Iss 2, Pp 234-242 (2016) |
| ISSN: | 2211-1247 |
| DOI: | 10.1016/j.celrep.2015.12.023 |
| Popis: | SummaryMice overexpressing the longevity protein SIRT6 or deficient for the liver’s most prevalent microRNA miR-122 display a similar set of phenotypes, including improved lipid profile and protection against damage linked to obesity. Here, we show that miR-122 and SIRT6 negatively regulate each other’s expression. SIRT6 downregulates miR-122 by deacetylating H3K56 in the promoter region. MiR-122 binds to three sites on the SIRT6 3′ UTR and reduces its levels. The interplay between SIRT6 and miR-122 is manifested in two physiologically relevant ways in the liver. First, they oppositely regulate a similar set of metabolic genes and fatty acid β-oxidation. Second, in hepatocellular carcinoma patients, loss of a negative correlation between SIRT6 and miR-122 expression is significantly associated with better prognosis. These findings show that SIRT6 and miR-122 negatively regulate each other to control various aspects of liver physiology and SIRT6-miR-122 correlation may serve as a biomarker for hepatocarcinoma prognosis. |
| Databáze: | OpenAIRE |
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