Reciprocal Regulation between SIRT6 and miR-122 Controls Liver Metabolism and Predicts Hepatocarcinoma Prognosis

Sivan Elhanati, Rotem Ben-Hamo, Yariv Kanfi, Alexander Varvak, Renana Glazz, Batia Lerrer, Sol Efroni, Haim Y. Cohen

نتاج البحث: نشر في مجلةمقالةمراجعة النظراء

76 اقتباسات (Scopus)

ملخص

Mice 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. Elhanati et al. find that SIRT6 and miR-122 negatively regulate each other. The interplay between them is linked to regulation of a shared set of metabolic genes and fatty acid β-oxidation and may present a biomarker for hepatocarcinoma prognosis.

اللغة الأصليةالإنجليزيّة
الصفحات (من إلى)234-242
عدد الصفحات9
دوريةCell Reports
مستوى الصوت14
رقم الإصدار2
المعرِّفات الرقمية للأشياء
حالة النشرنُشِر - 12 يناير 2016
منشور خارجيًانعم

بصمة

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