The Mina & Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 5290002, Israel.
The Mina & Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 5290002, Israel.
Cell Rep. 2016 Jan 12;14(2):234-42. doi: 10.1016/j.celrep.2015.12.023. Epub 2015 Dec 31.
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.
过表达长寿蛋白 SIRT6 或缺乏肝脏中最普遍的 microRNA miR-122 的小鼠表现出相似的表型，包括改善脂质谱和防止与肥胖相关的损伤。在这里，我们表明 miR-122 和 SIRT6 负调控彼此的表达。SIRT6 通过去乙酰化启动子区域的 H3K56 下调 miR-122。miR-122 结合到 SIRT6 3'UTR 的三个位点并降低其水平。SIRT6 和 miR-122 之间的相互作用在肝脏中以两种与生理相关的方式表现出来。首先，它们相反地调节相似的一组代谢基因和脂肪酸β氧化。其次，在肝细胞癌患者中，SIRT6 和 miR-122 表达之间负相关的丧失与更好的预后显著相关。这些发现表明，SIRT6 和 miR-122 相互负调控以控制肝脏生理学的各个方面，并且 SIRT6-miR-122 相关性可以作为肝细胞癌预后的生物标志物。
