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

doi:10.1016/j.celrep.2015.12.023

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

The Mina and Everard Goodman Faculty of Life Sciences - at Bar-Ilan University

Bar-Ilan University

Research output: Contribution to journal › Article › peer-review

84 Scopus citations

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. 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.

Original language	English
Pages (from-to)	234-242
Number of pages	9
Journal	Cell Reports
Volume	14
Issue number	2
DOIs	https://doi.org/10.1016/j.celrep.2015.12.023
State	Published - 12 Jan 2016

Bibliographical note

Publisher Copyright:
© 2016 The Authors.

Funding

We thank Shoshana Naiman and the members of the Cohen lab for their helpful comments on the manuscript. This study was supported by the Israel Science Foundation, I-Core Foundation, Israeli Ministry of Health, TEVA NNE program, ESFD, and the ERC: European Research Council.

Funders
ESFD
I-Core Foundation
Teva Pharmaceutical Industries
European Commission
Israel Science Foundation
Ministry of Health, State of Israel

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Fatty acid oxidation
SIRT6
miR-122

Access to Document

10.1016/j.celrep.2015.12.023

Cite this

@article{983a64639a6946728b76f15a14ccf3b3,

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. 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.",

keywords = "Fatty acid oxidation, SIRT6, miR-122",

author = "Sivan Elhanati and Rotem Ben-Hamo and Yariv Kanfi and Alexander Varvak and Renana Glazz and Batia Lerrer and Sol Efroni and Cohen, \{Haim Y.\}",

note = "Publisher Copyright: {\textcopyright} 2016 The Authors.",

year = "2016",

month = jan,

day = "12",

doi = "10.1016/j.celrep.2015.12.023",

language = "אנגלית",

volume = "14",

pages = "234--242",

journal = "Cell Reports",

issn = "2211-1247",

publisher = "Elsevier BV",

number = "2",

}

TY - JOUR

T1 - Reciprocal Regulation between SIRT6 and miR-122 Controls Liver Metabolism and Predicts Hepatocarcinoma Prognosis

AU - Elhanati, Sivan

AU - Ben-Hamo, Rotem

AU - Kanfi, Yariv

AU - Varvak, Alexander

AU - Glazz, Renana

AU - Lerrer, Batia

AU - Efroni, Sol

AU - Cohen, Haim Y.

PY - 2016/1/12

Y1 - 2016/1/12

N2 - 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.

AB - 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.

KW - Fatty acid oxidation

KW - SIRT6

KW - miR-122

UR - https://www.scopus.com/pages/publications/84955337844

U2 - 10.1016/j.celrep.2015.12.023

DO - 10.1016/j.celrep.2015.12.023

M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???

C2 - 26748705

SN - 2211-1247

VL - 14

SP - 234

EP - 242

JO - Cell Reports

JF - Cell Reports

IS - 2

ER -

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

Abstract

Bibliographical note

Funding

UN SDGs

Keywords

Access to Document

Other files and links

Fingerprint

Cite this