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miRNAs in non-alcoholic fatty liver disease |
Zhen He,Cheng Hu(),Weiping Jia |
Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai 200233, China |
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Abstract Non-alcoholic fatty liver disease (NAFLD) is a major cause of liver cirrhosis and hepatocellular carcinoma and is a considerable threat to public health. miRNAs are important post-transcriptional regulators of gene expression, and the dysregulation of miRNAs is involved in various biological processes in the liver, including lipid homeostasis, inflammation, apoptosis, and cell proliferation. Recently, a number of studies have described the association between miRNAs and NAFLD progression and have shown that circulating miRNAs reflect histological changes in the liver. Therefore, circulating miRNAs have potential use for the evaluation of NAFLD severity. In this review, we discuss the involvement of miRNAs in NAFLD pathogenesis and the key role of miRNAs in the screening, diagnosis, and staging of NAFLD.
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Keywords
nonalcoholic fatty liver disease
nonalcoholic steatohepatitis
hepatocellular carcinoma
miRNA
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Corresponding Author(s):
Cheng Hu
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Just Accepted Date: 19 August 2016
Online First Date: 28 September 2016
Issue Date: 01 December 2016
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1 |
Younossi ZM, Koenig AB, Abdelatif D, Fazel Y, Henry L, Wymer M. Global epidemiology of non-alcoholic fatty liver disease-meta-analytic assessment of prevalence, incidence and outcomes. Hepatology 2015; 64(1): 73–84
https://doi.org/DOI: 10.1002/hep.28431
pmid: 26707365
|
2 |
Vernon G, Baranova A, Younossi ZM. Systematic review: the epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults. Aliment Pharmacol Ther 2011; 34(3): 274–285
https://doi.org/10.1111/j.1365-2036.2011.04724.x
pmid: 21623852
|
3 |
Attar BM, Van Thiel DH. Current concepts and management approaches in nonalcoholic fatty liver disease. Sci World J 2013; 2013: 481893
https://doi.org/10.1155/2013/481893
pmid: 23576902
|
4 |
Yki-Järvinen H. Non-alcoholic fatty liver disease as a cause and a consequence of metabolic syndrome. Lancet Diabetes Endocrinol 2014; 2(11): 901–910
https://doi.org/10.1016/S2213-8587(14)70032-4
pmid: 24731669
|
5 |
Than NN, Newsome PN. A concise review of non-alcoholic fatty liver disease. Atherosclerosis 2015; 239(1): 192–202
https://doi.org/10.1016/j.atherosclerosis.2015.01.001
pmid: 25617860
|
6 |
Ul Hussain M. Micro-RNAs (miRNAs): genomic organisation, biogenesis and mode of action. Cell Tissue Res 2012; 349(2): 405–413
https://doi.org/10.1007/s00441-012-1438-0
pmid: 22622804
|
7 |
Wang XW, Heegaard NH, Orum H. MicroRNAs in liver disease. Gastroenterology 2012; 142(7): 1431–1443
https://doi.org/10.1053/j.gastro.2012.04.007
pmid: 22504185
|
8 |
Pirola CJ, Fernández Gianotti T, Castaño GO, Mallardi P, San Martino J, Mora Gonzalez Lopez Ledesma M, Flichman D, Mirshahi F, Sanyal AJ, Sookoian S. Circulating microRNA signature in non-alcoholic fatty liver disease: from serum non-coding RNAs to liver histology and disease pathogenesis. Gut 2015; 64(5): 800–812
https://doi.org/10.1136/gutjnl-2014-306996
pmid: 24973316
|
9 |
Li S, Chen X, Zhang H, Liang X, Xiang Y, Yu C, Zen K, Li Y, Zhang CY. Differential expression of microRNAs in mouse liver under aberrant energy metabolic status. J Lipid Res 2009; 50(9): 1756–1765
https://doi.org/10.1194/jlr.M800509-JLR200
pmid: 19372595
|
10 |
Cheung O, Puri P, Eicken C, Contos MJ, Mirshahi F, Maher JW, Kellum JM, Min H, Luketic VA, Sanyal AJ. Nonalcoholic steatohepatitis is associated with altered hepatic microRNA expression. Hepatology 2008; 48(6): 1810–1820
https://doi.org/10.1002/hep.22569
pmid: 19030170
|
11 |
Szabo G, Csak T. Role of microRNAs in NAFLD/NASH. Dig Dis Sci 2016; 61(5): 1314–1324
https://doi.org/10.1007/s10620-015-4002-4
pmid: 26769057
|
12 |
Tessitore A, Cicciarelli G, Del Vecchio F, Gaggiano A, Verzella D, Fischietti M, Mastroiaco V, Vetuschi A, Sferra R, Barnabei R, Capece D, Zazzeroni F, Alesse E. MicroRNA expression analysis in high fat diet-induced NAFLD-NASH-HCC progression: study on C57BL/6J mice. BMC Cancer 2016; 16(1): 3
https://doi.org/10.1186/s12885-015-2007-1
pmid: 26728044
|
13 |
Tsai WC, Hsu SD, Hsu CS, Lai TC, Chen SJ, Shen R, Huang Y, Chen HC, Lee CH, Tsai TF, Hsu MT, Wu JC, Huang HD, Shiao MS, Hsiao M, Tsou AP. MicroRNA-122 plays a critical role in liver homeostasis and hepatocarcinogenesis. J Clin Invest 2012; 122(8): 2884–2897
https://doi.org/10.1172/JCI63455
pmid: 22820290
|
14 |
Moore KJ, Rayner KJ, Suárez Y, Fernández-Hernando C. The role of microRNAs in cholesterol efflux and hepatic lipid metabolism. Annu Rev Nutr 2011; 31(1): 49–63
https://doi.org/10.1146/annurev-nutr-081810-160756
pmid: 21548778
|
15 |
Esau C, Davis S, Murray SF, Yu XX, Pandey SK, Pear M, Watts L, Booten SL, Graham M, McKay R, Subramaniam A, Propp S, Lollo BA, Freier S, Bennett CF, Bhanot S, Monia BP. miR-122 regulation of lipid metabolism revealed by in vivo antisense targeting. Cell Metab 2006; 3(2): 87–98
https://doi.org/10.1016/j.cmet.2006.01.005
pmid: 16459310
|
16 |
Csak T, Bala S, Lippai D, Satishchandran A, Catalano D, Kodys K, Szabo G. microRNA-122 regulates hypoxia-inducible factor-1 and vimentin in hepatocytes and correlates with fibrosis in diet-induced steatohepatitis. Liver Int 2015; 35(2): 532–541
https://doi.org/10.1111/liv.12633
pmid: 25040043
|
17 |
Horton JD, Goldstein JL, Brown MS. SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver. J Clin Invest 2002; 109(9): 1125–1131
https://doi.org/10.1172/JCI0215593
pmid: 11994399
|
18 |
Jeon TI, Osborne TF. SREBPs: metabolic integrators in physiology and metabolism. Trends Endocrinol Metab 2012; 23(2): 65–72
https://doi.org/10.1016/j.tem.2011.10.004
pmid: 22154484
|
19 |
Najafi-Shoushtari SH, Kristo F, Li Y, Shioda T, Cohen DE, Gerszten RE, Näär AM. MicroRNA-33 and the SREBP host genes cooperate to control cholesterol homeostasis. Science 2010; 328(5985): 1566–1569
https://doi.org/10.1126/science.1189123
pmid: 20466882
|
20 |
Dávalos A, Goedeke L, Smibert P, Ramírez CM, Warrier NP, Andreo U, Cirera-Salinas D, Rayner K, Suresh U, Pastor-Pareja JC, Esplugues E, Fisher EA, Penalva LO, Moore KJ, Suárez Y, Lai EC, Fernández-Hernando C. miR-33a/b contribute to the regulation of fatty acid metabolism and insulin signaling. Proc Natl Acad Sci USA 2011; 108(22): 9232–9237
https://doi.org/10.1073/pnas.1102281108
pmid: 21576456
|
21 |
Rayner KJ, Esau CC, Hussain FN, McDaniel AL, Marshall SM, van Gils JM, Ray TD, Sheedy FJ, Goedeke L, Liu X, Khatsenko OG, Kaimal V, Lees CJ, Fernandez-Hernando C, Fisher EA, Temel RE, Moore KJ. Inhibition of miR-33a/b in non-human primates raises plasma HDL and lowers VLDL triglycerides. Nature 2011; 478(7369): 404–407
https://doi.org/10.1038/nature10486
pmid: 22012398
|
22 |
Goedeke L, Salerno A, Ramírez CM, Guo L, Allen RM, Yin X, Langley SR, Esau C, Wanschel A, Fisher EA, Suárez Y, Baldán A, Mayr M, Fernández-Hernando C. Long-term therapeutic silencing of miR-33 increases circulating triglyceride levels and hepatic lipid accumulation in mice. EMBO Mol Med 2014; 6(9): 1133–1141
https://doi.org/10.15252/emmm.201404046
pmid: 25038053
|
23 |
Vega-Badillo J, Gutiérrez-Vidal R, Hernández-Pérez HA, Villamil-Ramírez H, León-Mimila P, Sánchez-Muñoz F, Morán-Ramos S, Larrieta-Carrasco E, Fernández-Silva I, Méndez-Sánchez N, Tovar AR, Campos-Pérez F, Villarreal-Molina T, Hernández-Pando R, Aguilar-Salinas CA, Canizales-Quinteros S. Hepatic miR-33a/miR-144 and their target gene ABCA1 are associated with steatohepatitis in morbidly obese subjects. Liver Int 2016 Mar 4. [Epub ahead of print]
https://doi.org/10.1111/liv.13109
pmid: 26945479
|
24 |
Cirera-Salinas D, Pauta M, Allen RM, Salerno AG, Ramírez CM, Chamorro-Jorganes A, Wanschel AC, Lasuncion MA, Morales-Ruiz M, Suarez Y, Baldan Á, <?Pub Caret1?>Esplugues E, Fernández-Hernando C. mir-33 regulates cell proliferation and cell cycle progression. Cell Cycle 2012; 11(5): 922–933
https://doi.org/10.4161/cc.11.5.19421
pmid: 22333591
|
25 |
Ding J, Li M, Wan X, Jin X, Chen S, Yu C, Li Y. Effect of miR-34a in regulating steatosis by targeting PPARa expression in nonalcoholic fatty liver disease. Sci Rep 2015; 5: 13729
https://doi.org/10.1038/srep13729
pmid: 26330104
|
26 |
Derdak Z, Villegas KA, Harb R, Wu AM, Sousa A, Wands JR. Inhibition of p53 attenuates steatosis and liver injury in a mouse model of non-alcoholic fatty liver disease. J Hepatol 2013; 58(4): 785–791
https://doi.org/10.1016/j.jhep.2012.11.042
pmid: 23211317
|
27 |
Xu Y, Zalzala M, Xu J, Li Y, Yin L, Zhang Y. A metabolic stress-inducible miR-34a-HNF4a pathway regulates lipid and lipoprotein metabolism. Nat Commun 2015; 6: 7466
https://doi.org/10.1038/ncomms8466
pmid: 26100857
|
28 |
Hayhurst GP, Lee YH, Lambert G, Ward JM, Gonzalez FJ. Hepatocyte nuclear factor 4α (nuclear receptor 2A1) is essential for maintenance of hepatic gene expression and lipid homeostasis. Mol Cell Biol 2001; 21(4): 1393–1403
https://doi.org/10.1128/MCB.21.4.1393-1403.2001
pmid: 11158324
|
29 |
Yin L, Ma H, Ge X, Edwards PA, Zhang Y. Hepatic hepatocyte nuclear factor 4a is essential for maintaining triglyceride and cholesterol homeostasis. Arterioscler Thromb Vasc Biol 2011; 31(2): 328–336
https://doi.org/10.1161/ATVBAHA.110.217828
pmid: 21071704
|
30 |
Shan W, Gao L, Zeng W, Hu Y, Wang G, Li M, Zhou J, Ma X, Tian X, Yao J.Activation of the SIRT1/p66shc antiapoptosis pathway via carnosic acid-induced inhibition of miR-34a protects rats against nonalcoholic fatty liver disease. Cell Death Dis 2015; 6: e1833
https://doi.org/10.1038/cddis.2015.196
pmid: 26203862
|
31 |
Sun C, Huang F, Liu X, Xiao X, Yang M, Hu G, Liu H, Liao L. miR-21 regulates triglyceride and cholesterol metabolism in non-alcoholic fatty liver disease by targeting HMGCR. Int J Mol Med 2015; 35(3): 847–853
pmid: 25605429
|
32 |
Ahn J, Lee H, Jung CH, Ha T. Lycopene inhibits hepatic steatosis via microRNA-21-induced downregulation of fatty acid-binding protein 7 in mice fed a high-fat diet. Mol Nutr Food Res 2012; 56(11): 1665–1674
https://doi.org/10.1002/mnfr.201200182
pmid: 22968990
|
33 |
Loyer X, Paradis V, Hénique C, Vion AC, Colnot N, Guerin CL, Devue C, On S, Scetbun J, Romain M, Paul JL, Rothenberg ME, Marcellin P, Durand F, Bedossa P, Prip-Buus C, Baugé E, Staels B, Boulanger CM, Tedgui A, Rautou PE. Liver microRNA-21 is overexpressed in non-alcoholic steatohepatitis and contributes to the disease in experimental models by inhibiting PPARa expression. Gut 2015 Sep 3. [Epub ahead of print]
https://doi.org/10.1136/gutjnl-2014-308883
pmid: 26338827
|
34 |
Reddy JK, Rao MS. Lipid metabolism and liver inflammation. II. Fatty liver disease and fatty acid oxidation. Am J Physiol Gastrointest Liver Physiol 2006; 290(5): G852–G858
https://doi.org/10.1152/ajpgi.00521.2005
pmid: 16603729
|
35 |
Yang L, Roh YS, Song J, Zhang B, Liu C, Loomba R, Seki E. Transforming growth factor beta signaling in hepatocytes participates in steatohepatitis through regulation of cell death and lipid metabolism in mice. Hepatology 2014; 59(2): 483–495
https://doi.org/10.1002/hep.26698
pmid: 23996730
|
36 |
Dattaroy D, Pourhoseini S, Das S, Alhasson F, Seth RK, Nagarkatti M, Michelotti GA, Diehl AM, Chatterjee S. MicroRNA 21 inhibition of SMAD7 enhances fibrogenesis via leptin-mediated NADPH oxidase in experimental and human nonalcoholic steatohepatitis. Am J Physiol Gastrointest Liver Physiol 2015; 308(4): G298–G312
https://doi.org/10.1152/ajpgi.00346.2014
pmid: 25501551
|
37 |
Wu H, Ng R, Chen X, Steer CJ, Song G. MicroRNA-21 is a potential link between non-alcoholic fatty liver disease and hepatocellular carcinoma via modulation of the HBP1-p53-Srebp1c pathway. Gut 2015 Aug 17. [Epub ahead of print]
https://doi.org/10.1136/gutjnl-2014-308430
pmid: 26282675
|
38 |
Vinciguerra M, Sgroi A, Veyrat-Durebex C, Rubbia-Brandt L, Buhler LH, Foti M. Unsaturated fatty acids inhibit the expression of tumor suppressor phosphatase and tensin homolog (PTEN) via microRNA-21 up-regulation in hepatocytes. Hepatology 2009; 49(4): 1176–1184
https://doi.org/10.1002/hep.22737
pmid: 19072831
|
39 |
He Y, Huang C, Lin X, Li J. MicroRNA-29 family, a crucial therapeutic target for fibrosis diseases. Biochimie 2013; 95(7): 1355–1359
https://doi.org/10.1016/j.biochi.2013.03.010
pmid: 23542596
|
40 |
Pogribny IP, Starlard-Davenport A, Tryndyak VP, Han T, Ross SA, Rusyn I, Beland FA. Difference in expression of hepatic microRNAs miR-29c, miR-34a, miR-155, and miR-200b is associated with strain-specific susceptibility to dietary nonalcoholic steatohepatitis in mice. Lab Invest 2010; 90(10): 1437–1446
https://doi.org/10.1038/labinvest.2010.113
pmid: 20548288
|
41 |
Mattis AN, Song G, Hitchner K, Kim RY, Lee AY, Sharma AD, Malato Y, McManus MT, Esau CC, Koller E, Koliwad S, Lim LP, Maher JJ, Raffai RL, Willenbring H. A screen in mice uncovers repression of lipoprotein lipase by microRNA-29a as a mechanism for lipid distribution away from the liver. Hepatology 2015; 61(1): 141–152
https://doi.org/10.1002/hep.27379
pmid: 25131933
|
42 |
Ahn J, Lee H, Chung CH, Ha T. High fat diet induced downregulation of microRNA-467b increased lipoprotein lipase in hepatic steatosis. Biochem Biophys Res Commun 2011; 414(4): 664–669
https://doi.org/10.1016/j.bbrc.2011.09.120
pmid: 21986524
|
43 |
Kurtz CL, Fannin EE, Toth CL, Pearson DS, Vickers KC, Sethupathy P. Inhibition of miR-29 has a significant lipid-lowering benefit through suppression of lipogenic programs in liver. Sci Rep 2015; 5: 12911
https://doi.org/10.1038/srep12911
pmid: 26246194
|
44 |
Xiao J, Bei Y, Liu J, Dimitrova-Shumkovska J, Kuang D, Zhou Q, Li J, Yang Y, Xiang Y, Wang F, Yang C, Yang W. miR-212 downregulation contributes to the protective effect of exercise against non-alcoholic fatty liver via targeting FGF-21. J Cell Mol Med 2016; 20(2): 204–216
https://doi.org/10.1111/jcmm.12733
pmid: 26648452
|
45 |
Zhang ZC, Liu Y, Xiao LL, Li SF, Jiang JH, Zhao Y, Qian SW, Tang QQ, Li X. Upregulation of miR-125b by estrogen protects against non-alcoholic fatty liver in female mice. J Hepatol 2015; 63(6): 1466–1475
https://doi.org/10.1016/j.jhep.2015.07.037
pmid: 26272872
|
46 |
Ng R, Wu H, Xiao H, Chen X, Willenbring H, Steer CJ, Song G. Inhibition of microRNA-24 expression in liver prevents hepatic lipid accumulation and hyperlipidemia. Hepatology 2014; 60(2): 554–564
https://doi.org/10.1002/hep.27153
pmid: 24677249
|
47 |
Wang B, Majumder S, Nuovo G, Kutay H, Volinia S, Patel T, Schmittgen TD, Croce C, Ghoshal K, Jacob ST. Role of microRNA-155 at early stages of hepatocarcinogenesis induced by choline-deficient and amino acid-defined diet in C57BL/6 mice. Hepatology 2009; 50(4): 1152–1161
https://doi.org/10.1002/hep.23100
pmid: 19711427
|
48 |
Lee SS, Park SH. Radiologic evaluation of nonalcoholic fatty liver disease. World J Gastroenterol 2014; 20(23): 7392–7402
https://doi.org/10.3748/wjg.v20.i23.7392
pmid: 24966609
|
49 |
Povero D, Eguchi A, Li H, Johnson CD, Papouchado BG, Wree A, Messer K, Feldstein AE. Circulating extracellular vesicles with specific proteome and liver microRNAs are potential biomarkers for liver injury in experimental fatty liver disease. PLoS ONE 2014; 9(12): e113651
https://doi.org/10.1371/journal.pone.0113651
pmid: 25470250
|
50 |
Yamada H, Suzuki K, Ichino N, Ando Y, Sawada A, Osakabe K, Sugimoto K, Ohashi K, Teradaira R, Inoue T, Hamajima N, Hashimoto S. Associations between circulating microRNAs (miR-21, miR-34a, miR-122 and miR-451) and non-alcoholic fatty liver. Clin Chim Acta 2013; 424: 99–103
https://doi.org/10.1016/j.cca.2013.05.021
pmid: 23727030
|
51 |
Yamada H, Ohashi K, Suzuki K, Munetsuna E, Ando Y, Yamazaki M, Ishikawa H, Ichino N, Teradaira R, Hashimoto S. Longitudinal study of circulating miR-122 in a rat model of non-alcoholic fatty liver disease. Clin Chim Acta 2015; 446: 267–271
https://doi.org/10.1016/j.cca.2015.05.002
pmid: 25958847
|
52 |
Clarke JD, Sharapova T, Lake AD, Blomme E, Maher J, Cherrington NJ. Circulating microRNA 122 in the methionine and choline-deficient mouse model of non-alcoholic steatohepatitis. J Appl Toxicol 2014; 34(6): 726–732
https://doi.org/10.1002/jat.2960
pmid: 24217942
|
53 |
Miyaaki H, Ichikawa T, Kamo Y, Taura N, Honda T, Shibata H, Milazzo M, Fornari F, Gramantieri L, Bolondi L, Nakao K. Significance of serum and hepatic microRNA-122 levels in patients with non-alcoholic fatty liver disease. Liver Int 2014; 34(7): e302–e307
https://doi.org/10.1111/liv.12429
pmid: 24313922
|
54 |
Cermelli S, Ruggieri A, Marrero JA, Ioannou GN, Beretta L. Circulating microRNAs in patients with chronic hepatitis C and non-alcoholic fatty liver disease. PLoS ONE 2011; 6(8): e23937
https://doi.org/10.1371/journal.pone.0023937
pmid: 21886843
|
55 |
Celikbilek M, Baskol M, Taheri S, Deniz K, Dogan S, Zararsiz G, Gursoy S, Guven K, Ozbakır O, Dundar M, Yucesoy M. Circulating microRNAs in patients with non-alcoholic fatty liver disease. World J Hepatol 2014; 6(8): 613–620
pmid: 25232454
|
56 |
Tan Y, Ge G, Pan T, Wen D, Gan J. A pilot study of serum microRNAs panel as potential biomarkers for diagnosis of nonalcoholic fatty liver disease. PLoS ONE 2014; 9(8): e105192
https://doi.org/10.1371/journal.pone.0105192
pmid: 25141008
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