Epigenetics in liver disease: from biology to therapeutics

被引:125
作者
Hardy, Timothy [1 ,2 ]
Mann, Derek A. [1 ]
机构
[1] Newcastle Univ, Inst Cellular Med, Fibrosis Labs, 4th Floor William Leech Bdg,Framlington Pl, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England
[2] Newcastle Upon Tyne Hosp NHS Fdn Trust, Dept Gastroenterol & Hepatol, Newcastle Upon Tyne, Tyne & Wear, England
基金
英国医学研究理事会;
关键词
HEPATIC STELLATE CELLS; ZESTE HOMOLOG 2; DNA METHYLATION; FATTY LIVER; HEPATOCELLULAR-CARCINOMA; GENOME-WIDE; MYOFIBROBLAST TRANSDIFFERENTIATION; TUMOR-SUPPRESSOR; CIRCADIAN-RHYTHM; LIPID-METABOLISM;
D O I
10.1136/gutjnl-2015-311292
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Knowledge of the fundamental epigenetic mechanisms governing gene expression and cellular phenotype are sufficiently advanced that novel insights into the epigenetic control of chronic liver disease are now emerging. Hepatologists are in the process of shedding light on the roles played by DNA methylation, histone/chromatin modifications and non-coding RNAs in specific liver pathologies. Alongside these discoveries are advances in the technologies for the detection and quantification of epigenetic biomarkers, either directly from patient tissue or from body fluids. The premise for this review is to survey the recent advances in the field of liver epigenetics and to explore their potential for translation by industry and clinical hepatologists for the design of novel therapeutics and diagnostic/ prognostic biomarkers. In particular, we present findings in the context of hepatocellular carcinoma, fibrosis and nonalcoholic fatty liver disease, where there is urgent unmet need for new clinical interventions and biomarkers.
引用
收藏
页码:1895 / 1905
页数:11
相关论文
共 130 条
[1]   Dietary resveratrol alters lipid metabolism-related gene expression of mice on an atherogenic diet [J].
Ahn, Jiyun ;
Cho, Iljin ;
Kim, Suna ;
Kwon, Daeyoung ;
Ha, Taeyoul .
JOURNAL OF HEPATOLOGY, 2008, 49 (06) :1019-1028
[2]   DNA Methylation Analysis in Nonalcoholic Fatty Liver Disease Suggests Distinct Disease-Specific and Remodeling Signatures after Bariatric Surgery [J].
Ahrens, Markus ;
Ammerpohl, Ole ;
von Schoenfels, Witigo ;
Kolarova, Julia ;
Bens, Susanne ;
Itzel, Timo ;
Teufel, Andreas ;
Herrmann, Alexander ;
Brosch, Mario ;
Hinrichsen, Holger ;
Erhart, Wiebke ;
Egberts, Jan ;
Sipos, Bence ;
Schreiber, Stefan ;
Haesler, Robert ;
Stickel, Felix ;
Becker, Thomas ;
Krawczak, Michael ;
Roecken, Christoph ;
Siebert, Reiner ;
Schafmayer, Clemens ;
Hampe, Jochen .
CELL METABOLISM, 2013, 18 (02) :296-302
[3]   Liver Fibrosis, but No Other Histologic Features, Is Associated With Long-term Outcomes of Patients With Nonalcoholic Fatty Liver Disease [J].
Angulo, Paul ;
Kleiner, David E. ;
Dam-Larsen, Sanne ;
Adams, Leon A. ;
Bjornsson, Einar S. ;
Charatcharoenwitthaya, Phunchai ;
Mills, Peter R. ;
Keach, Jill C. ;
Lafferty, Heather D. ;
Stahler, Alisha ;
Haflidadottir, Svanhildur ;
Bendtsen, Flemming .
GASTROENTEROLOGY, 2015, 149 (02) :389-+
[4]   The genetics of NAFLD [J].
Anstee, Quentin M. ;
Day, Christopher P. .
NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY, 2013, 10 (11) :645-655
[5]   Apoptosis on hepatoma cells but not on primary hepatocytes by histone deacetylase inhibitors valproate and ITF2357 [J].
Armeanu, S ;
Pathil, A ;
Venturelli, S ;
Mascagni, P ;
Weiss, TS ;
Göttlicher, M ;
Gregor, M ;
Lauer, UM ;
Bitzer, M .
JOURNAL OF HEPATOLOGY, 2005, 42 (02) :210-217
[6]   Enhancer of zeste homolog 2 epigenetically silences multiple tumor suppressor microRNAs to promote liver cancer metastasis [J].
Au, Sandy Leung-Kuen ;
Wong, Carmen Chak-Lui ;
Lee, Joyce Man-Fong ;
Fan, Dorothy Ngo-Yin ;
Tsang, Felice Hoching ;
Ng, Irene Oi-Lin ;
Wong, Chun-Ming .
HEPATOLOGY, 2012, 56 (02) :622-631
[7]   miR-122-A key factor and therapeutic target in liver disease [J].
Bandiera, Simonetta ;
Pfeffer, Sebastien ;
Baumert, Thomas F. ;
Zeisel, Mirjam B. .
JOURNAL OF HEPATOLOGY, 2015, 62 (02) :448-457
[8]   Liver fibrosis [J].
Bataller, R ;
Brenner, DA .
JOURNAL OF CLINICAL INVESTIGATION, 2005, 115 (02) :209-218
[9]   Resminostat plus sorafenib as second-line therapy of advanced hepatocellular carcinoma - The SHELTER study [J].
Bitzer, Michael ;
Horger, Marius ;
Giannini, Edoardo G. ;
Ganten, Tom M. ;
Woerns, Marcus A. ;
Siveke, Jens T. ;
Dollinger, Matthias M. ;
Gerken, Guido ;
Scheulen, Max E. ;
Wege, Henning ;
Zagonel, Vittorina ;
Cillo, Umberto ;
Trevisani, Franco ;
Santoro, Armando ;
Montesarchio, Vincenzo ;
Malek, Nisar P. ;
Holzapfel, Julia ;
Herz, Thomas ;
Ammendola, Astrid S. ;
Pegoraro, Stefano ;
Hauns, Bernhard ;
Mais, Anna ;
Lauer, Ulrich M. ;
Henning, Stefan W. ;
Hentsch, Bernd .
JOURNAL OF HEPATOLOGY, 2016, 65 (02) :280-288
[10]   Vitamin C induces Tet-dependent DNA demethylation and a blastocyst-like state in ES cells [J].
Blaschke, Kathryn ;
Ebata, Kevin T. ;
Karimi, Mohammad M. ;
Zepeda-Martinez, Jorge A. ;
Goyal, Preeti ;
Mahapatra, Sahasransu ;
Tam, Angela ;
Laird, Diana J. ;
Hirst, Martin ;
Rao, Anjana ;
Lorincz, Matthew C. ;
Ramalho-Santos, Miguel .
NATURE, 2013, 500 (7461) :222-+