miRNAs在肝脏疾病中的新进展
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摘要
微小RNA(miRNA)是一类内源基因编码的非编码单链RNA,它的主要作用是调控蛋白合成。关于miRNA在肝病中的作用一直是近年来的研究热点。已有大量研究发现miRNA在不同类型的肝病及在同一疾病的不同时期都有表达,miRNA检测对诊断和治疗肝病有重大帮助。该文就近年来关于miRNA在肝病中作用的研究进展作一综述。
MicroRNA(microRNA)is a kind of non-coding single-stranded RNA encoded by endogenous genes.Its main function is to regulate protein synthesis.The role of microRNAs in liver diseases has been a research hotspot in recent years.A large number of studies have found that microRNAs are expressed in different types of liver diseases and at different stages of the same disease.Detection of microRNAs is of great help in the diagnosis and treatment of liver diseases.This article reviews the research progress of the role of microRNAs in liver diseases in recent years.
MicroRNA(microRNA)is a kind of non-coding single-stranded RNA encoded by endogenous genes.Its main function is to regulate protein synthesis.The role of microRNAs in liver diseases has been a research hotspot in recent years.A large number of studies have found that microRNAs are expressed in different types of liver diseases and at different stages of the same disease.Detection of microRNAs is of great help in the diagnosis and treatment of liver diseases.This article reviews the research progress of the role of microRNAs in liver diseases in recent years.
引文
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[2] FAN J G.Epidemiology of alcoholic and nonalcoholic fatty liver disease in China[J].J Gastroenterol Hepatol,2013,28(Suppl 1):11-17.
[3] BARTEL D P.MicroRNAs:genomics,biogenesis,mechanism,and function[J].Cell,2004,116:281-297.
[4] CHEN Y J,ZHU J M,WU H,et al.Circulating microRNAs as a Fingerprint for Liver Cirrhosis[J].PLoS One,2013,8(6):e66577.
[5] WINTHER T N,BANG-BERTHELSEN C H,HEI BERG I L,et al.Differentialplasma microRNA profiles in HBeAg positive and HBeAg negative children with chronichepatitis B[J].PLoS One.2013;8(3):e58236.
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[8] XING T J,JIANG D F,HUANG J X,et al.Expression and clinical significance ofmiR-122and miR-29in hepatitis B virus-related liver disease[J].Genet Mol Res,2014,13(3):7912-7918.
[9] LIU A M,YAO T J,WANG W,et al.Circulating miR-15band miR-130bin serum as potential markers fordetecting hepatocellular carcinoma:a retrospective cohort study[J].BMJ Open,2012,2(2):e000825.
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[11]DHAYAT S A,HSING A,SENNINGER N,et al.Circulating microRNA-200family as diagnostic marker in hepatocellular carcinoma[J].PLoS One,2015,10(10):e0140066.
[12]LI H,SUN L,CHEN X,et al.Microvesicle microRNA profilesand functional roles between chronic hepatitis B and hepatocellular carcinoma[J].ClinTransl Oncol,2014,16(3):315-321.
[13]HUNG C H,HU T H,LU S N,et al.Circulating microRNAs as biomarkers for diagnosis of early hepatocellular carcinoma associated with hepatitis B virus[J].Int J Cancer,2016,138(3):714-720.
[14]SONG G,JIA H,XU H,et al.Studying the association of microRNA-210level with chronic hepatitis B progression[J].J ViralHepat,2014,21(4):272-280.
[15]YU F,CHEN B,FAN X,et al.Epigenetically-Regulated MicroRNA-9-5p Suppresses the Activation of Hepatic Stellate Cells via TGFBR1and TGFBR2[J].Cell Physiol Biochem,2017,43(6):2242-2252.
[16]FENG G X,LI J,YANG Z,et al.Hepatitis B virus X protein promotes the development of liver fibrosis and hepatoma through downregulation of miR-30e targeting P4HA2mRNA[J].Oncogene,2017,36(50):6895-6905.
[17]BIHRER V,FRIEDRICH-RUST M,KRONENBERGER B,et al.Serum miR-122as a biomarker of necroinflammation in patients with chronic hepatitis C virus infection[J].Am J Gastroenterol,2011,106(9):1663-1669.
[18]BIHRER V,WAIDMANN O,FRIEDRICH-RUST M,et al.Serum microRNA-21as marker for necroinflammation in hepatitis C patients with and without hepatocellularcarcinoma[J].PLoS One,2011,6(10):e26971.
[19]KUMAR S,CHAWLA Y K,GHOSH S,et al.Severity of hepatitis C virus(genotype-3)infection positively correlates with circulating microRNA-122in patients sera[J].Dis Markers,2014,2014:435476.
[20]MURAKAMI Y,TANAKA M,TOYODA H,et al.Hepatic microRNA expression is associated with the response to interferon treatment of chronic hepatitis C[J].BMC Med Genomics,2010,3:48.
[21]WAIDMANN O,BIHRER V,KRONENBERGER B,et al.Pretreatment serum microRNA-122is not predictive for treatment response in chronic hepatitis C virus infection[J].Dig Liver Dis,2012,44(5):438-441.
[22]SU T H,LIU C H,LIU C J,et al.Serum microRNA-122level correlates with virologic responses to pegylatedinterferon therapy in chronic hepatitis C[J].Proc Natl Acad Sci U S A,2013,110(19):7844-7849.
[23]BUTT A M,RAJA A J,SIDDIQUE S,et al.Parallel expression profiling of hepatic and serummicroRNA-122associated with clinical features and treatment responses in chronichepatitis C patients[J].Sci Rep,2016,6:21510.
[24]JARRET A,MCFARLAND A P,HORNER S M,et al.Hepatitis-C-virus-induced microRNAs dampen interferonmediated antiviral signaling[J].Nat Med 2016,22(12):1475-1481.
[25]ZHANG Y,WEI W,CHENG N,et al.Hepatitis C virusinduced up-regulation of microRNA-155promotes hepatocarcinogenesis by activating Wnt signaling[J].Hepatology,2012,56(5):1631-1640.
[26]ZHANG Z Q,MENG H,WANG N,et al.SerummicroRNA 143and microRNA 215as potential biomarkers for the diagnosis of chronichepatitis and hepatocellular carcinoma[J].Diagn Pathol,2014,9:135.
[27]CERMELLI S,RUGGIERI A,MARRERO J A,et al.CirculatingmicroRNAs in patients with chronic hepatitis C and non-alcoholic fatty liver disease[J].PLoS One,2011,6(8):e23937.
[28]MIYAAKI H,ICHIKAWA T,KAMO Y,et al.Significance of serum and hepaticmicroRNA-122levels in patients with non-alcoholic fatty liver disease[J].Liver Int,2014,34(7):e302-e307.
[29]PIROLA C J,FERNNDEZ GIANOTTI T,CASTA?O GO,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.
[30]WANG Y,DU J,NIU X,et al.MiR-130a-3p attenuates activation and induces apoptosis of hepatic stellate cells in nonalcoholic fibrosing steatohepatitis by directly targeting TGFBR1and TGFBR2[J].Cell Death Dis,2017,8(5):e2792.
[31]KIYOSHI M,ATSUMASA K,HIDEKO K,et al.Circulating microRNA Profiles in Patients with Type-1Autoimmune Hepatitis[J].PLoS One,2015,10(11):e0136908.
[32]MASASHI N,YASUTERU K,RYO F,et al.Distinct microRNAs expressionprofile in primary biliary cirrhosis and evaluation of miR 505-3p and miR197-3p asnovel biomarkers[J].PLoS One,2013,8(6):e66086.
[33]YOUWEN T,TENGLI P,YUN Y,et al.Serum microRNAs aspotential biomarkers of primary biliary cirrhosis[J].PLoS One,2014,9(10):e111424.
[34]KYRITSI K,MENG F,ZHOU T,et al.Knockdown of hepatic gonadotropin-releasing hormone by vivo-morpholino decreases liver fibrosis in multidrug resistance gene 2knockout mice by down-regulation of miR-200b[J].Am J Pathol,2017,187(7):1551-1565.
[35]WU N,MENG F,ZHOU T,et al.Prolonged darkness reduces liver fibrosis in a mouse model of primary sclerosing cholangitis by miR-200bdown-regulation[J].FASEB J,2017,31(10):4305-4324.
[36]CHEN Y P,JIN X,XIANG Z,et al.Circulating MicroRNAs aspotential biomarkers for alcoholic steatohepatitis[J].Liver Int,2013,33(8):1257-1265.
[37]CABANTOUS S,HOU X,LOUIS L,et al.Evidence for an important role of host microRNAs in regulating hepatic fibrosis in humans infected with Schistosoma japonicum[J].Int J Parasitol,2017,47(13):823-830.
[38]WANG Y,YANG F,XUE J,et al.Antischistosomiasis liver fibrosis effects of chlorogenic acid through IL-13/miR-21/Smad7signaling interactions in vivo and in vitro[J].Antimicrob Agents Chemother,2017,61(2).pii:e01347-16.
[2] FAN J G.Epidemiology of alcoholic and nonalcoholic fatty liver disease in China[J].J Gastroenterol Hepatol,2013,28(Suppl 1):11-17.
[3] BARTEL D P.MicroRNAs:genomics,biogenesis,mechanism,and function[J].Cell,2004,116:281-297.
[4] CHEN Y J,ZHU J M,WU H,et al.Circulating microRNAs as a Fingerprint for Liver Cirrhosis[J].PLoS One,2013,8(6):e66577.
[5] WINTHER T N,BANG-BERTHELSEN C H,HEI BERG I L,et al.Differentialplasma microRNA profiles in HBeAg positive and HBeAg negative children with chronichepatitis B[J].PLoS One.2013;8(3):e58236.
[6]JINATO T,CHUAYPEN N,POOMIPAK W,et al.Original Research:Analysis of hepatic microRNA alterations in response to hepatitis B virus infection andpegylated interferon alpha-2atreatment,[J].Exp Biol Med(Maywood),2016,241(16):1803-1810.
[7] SINGH A K,ROOGE S B,VARSHNEY A,et al.Global micro RNA expression profiling in the liver biopsies of hepatitis B Virus infected patients suggests specific miRNA signatures for viral persistence and hepatocellular injury[J].Hepatology,2017,67(5):1695-1709.
[8] XING T J,JIANG D F,HUANG J X,et al.Expression and clinical significance ofmiR-122and miR-29in hepatitis B virus-related liver disease[J].Genet Mol Res,2014,13(3):7912-7918.
[9] LIU A M,YAO T J,WANG W,et al.Circulating miR-15band miR-130bin serum as potential markers fordetecting hepatocellular carcinoma:a retrospective cohort study[J].BMJ Open,2012,2(2):e000825.
[10]GHOSH A,GHOSH A,DATTA S,et al.Hepatic miR-126is a potential plasma biomarker for detection of hepatitis B virus infected hepatocellular carcinoma[J].Int J Cancer,2016,138(11):2732-2744.
[11]DHAYAT S A,HSING A,SENNINGER N,et al.Circulating microRNA-200family as diagnostic marker in hepatocellular carcinoma[J].PLoS One,2015,10(10):e0140066.
[12]LI H,SUN L,CHEN X,et al.Microvesicle microRNA profilesand functional roles between chronic hepatitis B and hepatocellular carcinoma[J].ClinTransl Oncol,2014,16(3):315-321.
[13]HUNG C H,HU T H,LU S N,et al.Circulating microRNAs as biomarkers for diagnosis of early hepatocellular carcinoma associated with hepatitis B virus[J].Int J Cancer,2016,138(3):714-720.
[14]SONG G,JIA H,XU H,et al.Studying the association of microRNA-210level with chronic hepatitis B progression[J].J ViralHepat,2014,21(4):272-280.
[15]YU F,CHEN B,FAN X,et al.Epigenetically-Regulated MicroRNA-9-5p Suppresses the Activation of Hepatic Stellate Cells via TGFBR1and TGFBR2[J].Cell Physiol Biochem,2017,43(6):2242-2252.
[16]FENG G X,LI J,YANG Z,et al.Hepatitis B virus X protein promotes the development of liver fibrosis and hepatoma through downregulation of miR-30e targeting P4HA2mRNA[J].Oncogene,2017,36(50):6895-6905.
[17]BIHRER V,FRIEDRICH-RUST M,KRONENBERGER B,et al.Serum miR-122as a biomarker of necroinflammation in patients with chronic hepatitis C virus infection[J].Am J Gastroenterol,2011,106(9):1663-1669.
[18]BIHRER V,WAIDMANN O,FRIEDRICH-RUST M,et al.Serum microRNA-21as marker for necroinflammation in hepatitis C patients with and without hepatocellularcarcinoma[J].PLoS One,2011,6(10):e26971.
[19]KUMAR S,CHAWLA Y K,GHOSH S,et al.Severity of hepatitis C virus(genotype-3)infection positively correlates with circulating microRNA-122in patients sera[J].Dis Markers,2014,2014:435476.
[20]MURAKAMI Y,TANAKA M,TOYODA H,et al.Hepatic microRNA expression is associated with the response to interferon treatment of chronic hepatitis C[J].BMC Med Genomics,2010,3:48.
[21]WAIDMANN O,BIHRER V,KRONENBERGER B,et al.Pretreatment serum microRNA-122is not predictive for treatment response in chronic hepatitis C virus infection[J].Dig Liver Dis,2012,44(5):438-441.
[22]SU T H,LIU C H,LIU C J,et al.Serum microRNA-122level correlates with virologic responses to pegylatedinterferon therapy in chronic hepatitis C[J].Proc Natl Acad Sci U S A,2013,110(19):7844-7849.
[23]BUTT A M,RAJA A J,SIDDIQUE S,et al.Parallel expression profiling of hepatic and serummicroRNA-122associated with clinical features and treatment responses in chronichepatitis C patients[J].Sci Rep,2016,6:21510.
[24]JARRET A,MCFARLAND A P,HORNER S M,et al.Hepatitis-C-virus-induced microRNAs dampen interferonmediated antiviral signaling[J].Nat Med 2016,22(12):1475-1481.
[25]ZHANG Y,WEI W,CHENG N,et al.Hepatitis C virusinduced up-regulation of microRNA-155promotes hepatocarcinogenesis by activating Wnt signaling[J].Hepatology,2012,56(5):1631-1640.
[26]ZHANG Z Q,MENG H,WANG N,et al.SerummicroRNA 143and microRNA 215as potential biomarkers for the diagnosis of chronichepatitis and hepatocellular carcinoma[J].Diagn Pathol,2014,9:135.
[27]CERMELLI S,RUGGIERI A,MARRERO J A,et al.CirculatingmicroRNAs in patients with chronic hepatitis C and non-alcoholic fatty liver disease[J].PLoS One,2011,6(8):e23937.
[28]MIYAAKI H,ICHIKAWA T,KAMO Y,et al.Significance of serum and hepaticmicroRNA-122levels in patients with non-alcoholic fatty liver disease[J].Liver Int,2014,34(7):e302-e307.
[29]PIROLA C J,FERNNDEZ GIANOTTI T,CASTA?O GO,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.
[30]WANG Y,DU J,NIU X,et al.MiR-130a-3p attenuates activation and induces apoptosis of hepatic stellate cells in nonalcoholic fibrosing steatohepatitis by directly targeting TGFBR1and TGFBR2[J].Cell Death Dis,2017,8(5):e2792.
[31]KIYOSHI M,ATSUMASA K,HIDEKO K,et al.Circulating microRNA Profiles in Patients with Type-1Autoimmune Hepatitis[J].PLoS One,2015,10(11):e0136908.
[32]MASASHI N,YASUTERU K,RYO F,et al.Distinct microRNAs expressionprofile in primary biliary cirrhosis and evaluation of miR 505-3p and miR197-3p asnovel biomarkers[J].PLoS One,2013,8(6):e66086.
[33]YOUWEN T,TENGLI P,YUN Y,et al.Serum microRNAs aspotential biomarkers of primary biliary cirrhosis[J].PLoS One,2014,9(10):e111424.
[34]KYRITSI K,MENG F,ZHOU T,et al.Knockdown of hepatic gonadotropin-releasing hormone by vivo-morpholino decreases liver fibrosis in multidrug resistance gene 2knockout mice by down-regulation of miR-200b[J].Am J Pathol,2017,187(7):1551-1565.
[35]WU N,MENG F,ZHOU T,et al.Prolonged darkness reduces liver fibrosis in a mouse model of primary sclerosing cholangitis by miR-200bdown-regulation[J].FASEB J,2017,31(10):4305-4324.
[36]CHEN Y P,JIN X,XIANG Z,et al.Circulating MicroRNAs aspotential biomarkers for alcoholic steatohepatitis[J].Liver Int,2013,33(8):1257-1265.
[37]CABANTOUS S,HOU X,LOUIS L,et al.Evidence for an important role of host microRNAs in regulating hepatic fibrosis in humans infected with Schistosoma japonicum[J].Int J Parasitol,2017,47(13):823-830.
[38]WANG Y,YANG F,XUE J,et al.Antischistosomiasis liver fibrosis effects of chlorogenic acid through IL-13/miR-21/Smad7signaling interactions in vivo and in vitro[J].Antimicrob Agents Chemother,2017,61(2).pii:e01347-16.