title: Reciprocal Regulation between SIRT6 and miR-122 Controls Liver Metabolism and Predicts Hepatocarcinoma Prognosis.
abstract: 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.
authors.affiliation: The Mina & Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 5290002, Israel.
authors.forename: Sivan
authors.initials: S
authors.lastname: Elhanati
authors.affiliation: The Mina & Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 5290002, Israel.
authors.forename: Rotem
authors.initials: R
authors.lastname: Ben-Hamo
authors.affiliation: The Mina & Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 5290002, Israel.
authors.forename: Yariv
authors.initials: Y
authors.lastname: Kanfi
authors.affiliation: The Mina & Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 5290002, Israel.
authors.forename: Alexander
authors.initials: A
authors.lastname: Varvak
authors.affiliation: The Mina & Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 5290002, Israel.
authors.forename: Renana
authors.initials: R
authors.lastname: Glazz
authors.affiliation: The Mina & Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 5290002, Israel.
authors.forename: Batia
authors.initials: B
authors.lastname: Lerrer
authors.affiliation: The Mina & Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 5290002, Israel.
authors.forename: Sol
authors.initials: S
authors.lastname: Efroni
authors.affiliation: The Mina & Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 5290002, Israel. Electronic address: haim.cohen@biu.ac.il.
authors.forename: Haim Y
authors.initials: HY
authors.lastname: Cohen
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D005227:Fatty Acids / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000473:pathology*; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D010084:Oxidation-Reduction; D011379:Prognosis; D037761:Sirtuins / Q000235:genetics* / Q000378:metabolism*
chemical_list: D005227:Fatty Acids; C531907:MIRN122 microRNA, human; D035683:MicroRNAs; C516592:SIRT6 protein, human; D037761:Sirtuins
keywords: SIRT6; fatty acid oxidation; miR-122