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摘要: 非酒精性脂肪性肝病(nonalcoholic fatty liver disease,NAFLD)是一种最常见的慢性肝病,全球患病率约为30.05%~32.40%,并且与多种其他疾病密切相关。近年来,miRNA(microRNA,miRNA)作为无创生物标志物在NAFLD的发病机制和诊断中扮演了重要角色。miRNA是一种小分子RNA,通过控制靶基因的转录和翻译来调节基因表达和蛋白质合成。miRNA在脂肪代谢和胰岛素抵抗中都起着重要作用,并在NAFLD的发病机制中发挥着具体的调控角色。就miRNA在脂肪代谢、胰岛素抵抗、NAFLD发生发展中的作用及机制的作一综述。Abstract: Nonalcoholic fatty liver disease(NAFLD) is the most common chronic liver disease, with a global prevalence of approximately 30.05% to 32.4%. It is closely associated with various other diseases. In recent years, microRNAs(miRNAs) have played a crucial role as non-invasive biomarkers in understanding the pathogenesis and diagnosis of NAFLD. miRNAs play significant roles in both lipid metabolism and insulin resistance, exerting specific regulatory functions in the development and progression of NAFLD. miRNAs are small RNA molecules that regulate the gene expression and protein synthesis by controlling the transcription and translation of target genes. This article provides a comprehensive overview of the roles and mechanisms of miRNAs in lipid metabolism, insulin resistance, and the occurrence and development of NAFLD.
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Key words:
- Nonalcoholic fatty liver disease /
- miRNA /
- Insulin Resistance
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[1] Rinella M E,Neuschwander-Tetri B A,Siddiqui M S,et al. AASLD practice guidance on the clinical assessment and management of nonalcoholic fatty liver disease[J]. Hepatology,2023,77(5):1797-1835. doi: 10.1097/HEP.0000000000000323 [2] Cotter T G,Rinella M. Nonalcoholic fatty liver disease 2020: The state of the disease[J]. Gastroenterology,2020,158(7):1851-1864. doi: 10.1053/j.gastro.2020.01.052 [3] Powell E E,Wong V W,Rinella M. Non-alcoholic fatty liver disease[J]. Lancet,2021,397(10290):2212-2224. doi: 10.1016/S0140-6736(20)32511-3 [4] Younossi Z M,Golabi P,Paik J M,et al. The global epidemiology of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH): A systematic review[J]. Hepatology,2023,77(4):1335-1347. doi: 10.1097/HEP.0000000000000004 [5] Riazi K,Azhari H,Charette J H,et al. The prevalence and incidence of NAFLD worldwide: A systematic review and meta-analysis[J]. Lancet Gastroenterol Hepatol,2022,7(9):851-861. doi: 10.1016/S2468-1253(22)00165-0 [6] Li J,Zou B,Yeo Y H,et al. Prevalence,incidence,and outcome of non-alcoholic fatty liver disease in Asia,1999–2019: A systematic review and meta-analysis[J]. The Lancet Gastroenterology & Hepatology,2019,4(5):389-398. [7] Saliminejad K,Khorram Khorshid H R,Soleymani Fard S,et al. An overview of microRNAs: Biology,functions,therapeutics,and analysis methods[J]. J Cell Physiol,2019,234(5):5451-5465. doi: 10.1002/jcp.27486 [8] Shi Y,Liu Z,Lin Q,et al. MiRNAs and cancer: Key link in diagnosis and therapy[J]. Genes (Basel),2021,12(8):1289-1302. doi: 10.3390/genes12081289 [9] Feng Y,Li J,Zhang Y. Chemical knockdown of microRNA with small-molecule chimeras[J]. Chembiochem,2020,21(22):3180-3185. doi: 10.1002/cbic.202000287 [10] Chen P S,Lin S C,Tsai S J. Complexity in regulating microRNA biogenesis in cancer[J]. Exp Biol Med (Maywood),2020,245(5):395-401. doi: 10.1177/1535370220907314 [11] Hill M,Tran N. miRNA interplay: Mechanisms and consequences in cancer[J]. Dis Model Mech,2021,14(4):1-4. doi: 10.1242/dmm.047662 [12] Bartel D P. Metazoan microRNAs[J]. Cell,2018,173(1):20-51. doi: 10.1016/j.cell.2018.03.006 [13] Jie M,Feng T,Huang W,et al. Subcellular localization of miRNAs and implications in cellular homeostasis[J]. Genes (Basel),2021,12(6):856. doi: 10.3390/genes12060856 [14] Arguello G,Balboa E,Arrese M,et al. Recent insights on the role of cholesterol in non-alcoholic fatty liver disease[J]. Biochim Biophys Acta,2015,1852(9):1765-1778. doi: 10.1016/j.bbadis.2015.05.015 [15] Pang L,Liu K,Liu D,et al. Differential effects of reticulophagy and mitophagy on nonalcoholic fatty liver disease[J]. Cell Death Dis,2018,9(2):90. doi: 10.1038/s41419-017-0136-y [16] Teratani T, Tomita K, Suzuki T, et al. A high-cholesterol diet exacerbates liver fibrosis in mice via accumulation of free cholesterol in hepatic stellate cells[J]. Gastroenterology, 2012, 142(1): 152-164 e10 [17] Pirola C J,Fernandez Gianotti T,Castano G O,et al. Circulating microRNA signature in non-alcoholic fatty liver disease: from serum non-coding RNAs to liver histology and disease pathogenesis[J]. Gut,2015,64(5):800-812. doi: 10.1136/gutjnl-2014-306996 [18] Laudadio I,Manfroid I,Achouri Y,et al. A feedback loop between the liver-enriched transcription factor network and miR-122 controls hepatocyte differentiation[J]. Gastroenterology,2012,142(1):119-129. doi: 10.1053/j.gastro.2011.09.001 [19] Becker P P,Rau M,Schmitt J,et al. Performance of serum microRNAs -122,-192 and -21 as biomarkers in Patients with non-alcoholic steatohepatitis[J]. PLoS One,2015,10(11):e0142661. doi: 10.1371/journal.pone.0142661 [20] Esau C,Davis S,Murray S F,et al. miR-122 regulation of lipid metabolism revealed by in vivo antisense targeting[J]. Cell Metab,2006,3(2):87-98. doi: 10.1016/j.cmet.2006.01.005 [21] Krutzfeldt J,Rajewsky N,Braich R,et al. Silencing of microRNAs in vivo with 'antagomirs'[J]. Nature,2005,438(7068):685-689. doi: 10.1038/nature04303 [22] Vega-Badillo J,Gutierrez-Vidal R,Hernandez-Perez H A,et al. Hepatic miR-33a/miR-144 and their target gene ABCA1 are associated with steatohepatitis in morbidly obese subjects[J]. Liver Int,2016,36(9):1383-1391. doi: 10.1111/liv.13109 [23] Wu H,Ng R,Chen X,et al. MicroRNA-21 is a potential link between non-alcoholic fatty liver disease and hepatocellular carcinoma via modulation of the HBP1-p53-Srebp1c pathway[J]. Gut,2016,65(11):1850-1860. doi: 10.1136/gutjnl-2014-308430 [24] Rodrigues P M,Afonso M B,Simao A L,et al. miR-21 ablation and obeticholic acid ameliorate nonalcoholic steatohepatitis in mice[J]. Cell Death Dis,2017,8(4):e2748. doi: 10.1038/cddis.2017.172 [25] Sun C,Huang F,Liu X,et al. miR-21 regulates triglyceride and cholesterol metabolism in non-alcoholic fatty liver disease by targeting HMGCR[J]. International Journal of Molecular Medicine,2015,35(3):847-853. doi: 10.3892/ijmm.2015.2076 [26] Ahn J,Lee H,Jung C H,et al. Lycopene inhibits hepatic steatosis via microRNA-21-induced downregulation of fatty acid-binding protein 7 in mice fed a high-fat diet[J]. Mol Nutr Food Res,2012,56(11):1665-74. doi: 10.1002/mnfr.201200182 [27] Yang Y,Guo J X,Shao Z Q. miR-21 targets and inhibits tumor suppressor gene PTEN to promote prostate cancer cell proliferation and invasion: An experimental study[J]. Asian Pac J Trop Med,2017,10(1):87-91. doi: 10.1016/j.apjtm.2016.09.011 [28] Lin Y,Ding D,Huang Q,et al. Downregulation of miR-192 causes hepatic steatosis and lipid accumulation by inducing SREBF1: Novel mechanism for bisphenol A-triggered non-alcoholic fatty liver disease[J]. Biochim Biophys Acta Mol Cell Biol Lipids,2017,1862(9):869-882. [29] Borji M,Nourbakhsh M,Shafiee S M,et al. Down-regulation of SIRT1 expression by mir-23b contributes to lipid accumulation in HepG2 cells[J]. Biochem Genet,2019,57(4):507-521. doi: 10.1007/s10528-019-09905-5 [30] Ali O,Darwish H A,Eldeib K M,et al. miR-26a Potentially contributes to the regulation of fatty acid and sterol metabolism in vitro human hepG2 cell model of nonalcoholic fatty liver disease[J]. Oxid Med Cell Longev,2018,2018(1):8515343. [31] Xu Y,Zalzala M,Xu J,et al. A metabolic stress-inducible miR-34a-HNF4alpha pathway regulates lipid and lipoprotein metabolism[J]. Nat Commun,2015,6(1):7466. doi: 10.1038/ncomms8466 [32] Jia N,Lin X,Ma S,et al. Amelioration of hepatic steatosis is associated with modulation of gut microbiota and suppression of hepatic miR-34a in gynostemma pentaphylla (Thunb. ) makino treated mice[J]. Nutr Metab (Lond),2018,15(1):86. doi: 10.1186/s12986-018-0323-6 [33] Zeng N,Huang R,Li N,et al. MiR-451a attenuates free fatty acids-mediated hepatocyte steatosis by targeting the thyroid hormone responsive spot 14 gene[J]. Mol Cell Endocrinol,2018,474(1):260-271. [34] Zhang T,Zhao X,Steer C J,et al. A negative feedback loop between microRNA-378 and Nrf1 promotes the development of hepatosteatosis in mice treated with a high fat diet[J]. Metabolism,2018,85(1):183-191. [35] Lei L,Zhou C,Yang X,et al. Down-regulation of microRNA-375 regulates adipokines and inhibits inflammatory cytokines by targeting AdipoR2 in non-alcoholic fatty liver disease[J]. Clin Exp Pharmacol Physiol,2018,45(8):819-831. doi: 10.1111/1440-1681.12940 [36] Guo J,Dou L,Meng X,et al. Hepatic miR-291b-3p mediated glucose metabolism by directly targeting p65 to upregulate PTEN expression[J]. Sci Rep,2017,7(1):39899. doi: 10.1038/srep39899 [37] Xu L,Li Y,Yin L,et al. miR-125a-5p ameliorates hepatic glycolipid metabolism disorder in type 2 diabetes mellitus through targeting of STAT3[J]. Theranostics,2018,8(20):5593-5609. doi: 10.7150/thno.27425 [38] Jordan S D,Kruger M,Willmes D M,et al. Obesity-induced overexpression of miRNA-143 inhibits insulin-stimulated AKT activation and impairs glucose metabolism[J]. Nat Cell Biol,2011,13(4):434-446. doi: 10.1038/ncb2211 [39] Yang W M,Min K H,Lee W. Induction of miR-96 by dietary saturated fatty acids exacerbates hepatic insulin resistance through the suppression of INSR and IRS-1[J]. PLoS One,2016,11(12):e0169039. doi: 10.1371/journal.pone.0169039 [40] Jampoka K,Muangpaisarn P,Khongnomnan K,et al. Serum miR-29a and miR-122 as potential biomarkers for non-alcoholic fatty liver disease (NAFLD)[J]. Microrna,2018,7(3):215-222. doi: 10.2174/2211536607666180531093302 [41] Ramirez C M,Goedeke L,Rotllan N,et al. MicroRNA 33 regulates glucose metabolism[J]. Mol Cell Biol,2013,33(15):2891-2902. doi: 10.1128/MCB.00016-13 [42] Garcia-Jacobo R E,Uresti-Rivera E E,Portales-Perez D P,et al. Circulating miR-146a,miR-34a and miR-375 in type 2 diabetes patients,pre-diabetic and normal-glycaemic individuals in relation to beta-cell function,insulin resistance and metabolic parameters[J]. Clin Exp Pharmacol Physiol,2019,46(12):1092-1100. doi: 10.1111/1440-1681.13147 [43] Zhou M,Hou Y,Wu J,et al. miR-93-5p promotes insulin resistance to regulate type 2 diabetes progression in HepG2 cells by targeting HGF[J]. Mol Med Rep,2021,23(5):329. doi: 10.3892/mmr.2021.11968 [44] Santos D,Porter-Gill P,Goode G,et al. Circulating microRNA levels differ in the early stages of insulin resistance in prepubertal children with obesity[J]. Life Sci,2023,312(1):121246. [45] Dai L L,Li S D,Ma Y C,et al. MicroRNA-30b regulates insulin sensitivity by targeting SERCA2b in non-alcoholic fatty liver disease[J]. Liver Int,2019,39(8):1504-1513. doi: 10.1111/liv.14067 [46] Zhang C,Wang P,Li Y,et al. Role of microRNAs in the development of hepatocellular carcinoma in nonalcoholic fatty liver disease[J]. Anat Rec (Hoboken),2019,302(2):193-200. doi: 10.1002/ar.23954 [47] Torres J L,Novo-Veleiro I,Manzanedo L,et al. Role of microRNAs in alcohol-induced liver disorders and non-alcoholic fatty liver disease[J]. World J Gastroenterol,2018,24(36):4104-4118. doi: 10.3748/wjg.v24.i36.4104 [48] Wang X, He Y, Mackowiak B, et al. MicroRNAs as regulators, biomarkers and therapeutic targets in liver diseases[J]. Gut, 2021, 70(4): 784-795 [49] Zhang Z, Moon R, Thorne J L, et al. NAFLD and vitamin D: Evidence for intersection of microRNA-regulated pathways[J]. Nutr Res Rev, 2021,36(1): 1-20 [50] Serino M. Molecular paths linking metabolic diseases,gut microbiota dysbiosis and enterobacteria infections[J]. J Mol Biol,2018,430(5):581-590. doi: 10.1016/j.jmb.2018.01.010 [51] Gjorgjieva M,Sobolewski C,Dolicka D,et al. miRNAs and NAFLD: From pathophysiology to therapy[J]. Gut,2019,68(11):2065-2079. doi: 10.1136/gutjnl-2018-318146 [52] Xin S,Zhan Q,Chen X,et al. Efficacy of serum miRNA test as a non-invasive method to diagnose nonalcoholic steatohepatitis: A systematic review and meta-analysis[J]. BMC Gastroenterol,2020,20(1):186. doi: 10.1186/s12876-020-01334-8 [53] Jonas W,Schurmann A. Genetic and epigenetic factors determining NAFLD risk[J]. Mol Metab,2021,50(1):101111. [54] Kiran S,Kumar V,Kumar S,et al. Adipocyte,immune cells,and miRNA crosstalk: A novel regulator of metabolic dysfunction and obesity[J]. Cells,2021,10(5):1004. doi: 10.3390/cells10051004 [55] Shen Y,Cheng L,Xu M,et al. SGLT2 inhibitor empagliflozin downregulates miRNA-34a-5p and targets GREM2 to inactivate hepatic stellate cells and ameliorate non-alcoholic fatty liver disease-associated fibrosis[J]. Metabolism,2023,146(1):155657. [56] Kan Changez M I, Mubeen M, Zehra M, et al. Role of microRNA in non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH): A comprehensive review[J]. J Int Med Res, 2023, 51(9): 3000605231197058.
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