The regulatory role of microRNA-1187 in TNF-α-mediated hepatocyte apoptosis in acute liver failure

Yu,Dong  Shan; An,Fang  Mei; Gong,Bang  Dong; Xiang,Xiao  Gang; Lin,Lan  Yi; Wang,Hui; Xie,Qing

doi:10.3892/ijmm.2012.888

The regulatory role of microRNA-1187 in TNF-α-mediated hepatocyte apoptosis in acute liver failure

Authors:
- Dong Shan Yu
- Fang Mei An
- Bang Dong Gong
- Xiao Gang Xiang
- Lan Yi Lin
- Hui Wang
- Qing Xie
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Affiliations: Department of Infectious Disease, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, P.R. China, Department of Infectious Disease, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Ruijin er Road, no. 197, Shanghai 200025, P.R. China
Published online on: January 17, 2012 https://doi.org/10.3892/ijmm.2012.888
Pages: 663-668

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Abstract

In the current study, we aimed at elucidating the regulatory mechanisms through which microR-1187 (miR-1187) participates in hepatocyte apoptosis in acute liver failure (ALF). An ALF model was induced with D-galactosamine (D-GalN) plus lipopolysaccharide (LPS) in BALB/c mice. The hepatic miRNA expression profile was detected by microarray analysis and verified by quantitative real-time PCR (qRT-PCR). The possible underlying mechanism was investigated in vitro using an embryonic murine hepatocyte cell line (BNLCL2) and miR-1187 mimic. Caspase-8 protein was detected by Western blotting and cell apoptosis was assayed by flow cytometry. Hepatic miR-1187 was down-regulated in ALF mice based on microarray data (P<0.001) and verified by qRT-PCR (P<0.01). Target scan revealed that caspase-8 was the putative target of miR-1187. In an in vitro study, miR-1187 showed the highest up-regulation in BNLCL2 cells transfected with the miR-1187 mimic at a 50 nM concentration for 12 h compared with cells transfected with the non-specific mimic (P<0.001). miR-1187 was down-regulated (P<0.01) but caspase-8 mRNA (P<0.01) as well as protein (P<0.05) were up-regulated in the BNLCL2 cells treated with D-GalN/TNF. Furthermore, overexpressed miR-1187 reduced caspase-8 expression at both the mRNA and protein levels significantly (P<0.01 and P<0.05 respectively), and significantly attenuated the apoptotic rate of BNLCL2 cells (P<0.05). We show that miR-1187 regulates hepatocyte apoptosis by targeting caspase-8. miR-1187 may serve as a potential therapeutic target for the treatment of ALF.

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1	JG O’GradyAcute liver failurePostgrad Med J811481542005
2	HC LeeAcute liver failure related to hepatitis B virusHepatol Res38S9S13200810.1111/j.1872-034X.2008.00420.x19125959
3	Z ZhangZS ZouJL FuSevere dendritic cell perturbation is actively involved in the pathogenesis of acute-on-chronic hepatitis B liver failureJ Hepatol49396406200810.1016/j.jhep.2008.05.01718644645
4	K RyoY KamogawaI IkedaSignificance of Fas antigen-mediated apoptosis in human fulminant hepatic failureAm J Gastroenterol9520472055200010.1111/j.1572-0241.2000.02268.x10950056
5	B AlbertsA JohnsonJ LewisMolecular Biology of the Cell4th editionGarland ScienceNew York2002
6	Y AkazawaGJ GoresDeath receptor-mediated liver injurySemin Liver Dis27327338200710.1055/s-2007-99151017979070
7	ME GuicciardiGJ GoresApoptosis: a mechanism of acute and chronic liver injuryGut5410241033200510.1136/gut.2004.05385015951554
8	H MalhiGJ GoresCellular and molecular mechanisms of liver injuryGastroenterology13416411654200810.1053/j.gastro.2008.03.00218471544
9	SM ElbashirJ HarborthW LendeckelDuplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cellsNature411494498200110.1038/3507810711373684
10	M YangY LiRW PadgettMicroRNAs: small regulators with a big impactCytokine Growth Factor Rev16387393200510.1016/j.cytogfr.2005.02.00815869899
11	KD TaganovMP BoldinD BaltimoreMicroRNAs and immunity: tiny player in a big fieldImmunity26133137200710.1016/j.immuni.2007.02.00517307699
12	S UraM HondaT YamashitaDifferential microRNA expression between hepatitis B and hepatitis C leading disease progression to hepatocellular carcinomaHepatology4910981112200910.1002/hep.2274919173277
13	O CheungP PuriC EickenNonalcoholic steatohepatitis is associated with altered hepatic microRNA expressionHepatology4818101820200810.1002/hep.2256919030170
14	RE LanfordES Hildebrandt-EriksenA PetriTherapeutic silencing of microRNA-122 in primates with chronic hepatitis C virus infectionScience327198201201010.1126/science.117817819965718
15	BK YooPK SanthekadurR GredlerIncreased RNA-induced silencing complex (RISC) activity contributes to hepatocellular carcinomaHepatology5315381548201110.1002/hep.2421621520169
16	FM AnDS YuQ XieThe role of miRNA-122 expression during the acute liver failure in mice induced by D-GalN/LPSZhonghua Gan Zang Bing Za Zhi185275322010(in Chinese)
17	FM AnDS YuBD GongThe expression profile and roles of microRNA in tumor necrosis factor-α mediated acute liver failure in mouse modelChin J Infect Dis285495542010(In Chinese)
18	H MatsumotoS TamuraY KamadaAdiponectin deficiency exacerbates lipopolysaccharide/D-galactosamine-induced liver injury in miceWorld J Gastroenterol1233523358200616733851
19	BD GongQ XieL WangReal-time quantification of microRNAs in Huh7 cells by stem-loop reverse transcriptase polymerase chain reactionZhonghua Gan Zang Bing Za Zhi176036062009(In Chinese)
20	KJ LivakTD SchmittgenAnalysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) methodMethods25402408200110.1006/meth.2001.126211846609
21	MA ReddySD ShuklaPotentiation of mitogen-activated protein kinase by ethanol in embryonic liver cellsBiochem Pharmacol51661668199610.1016/S0006-2952(95)02239-28615903
22	GQ ZhangH YuXQ ZhouTNF-α induced apoptosis and necrosis of mice hepatocytesWorld Chinese J Digestol83033062000(In Chinese)
23	E HatanoTumor necrosis factor signaling in hepatocyte apoptosisJ Gastroenterol Hepatol22S43S44200710.1111/j.1440-1746.2006.04645.x17567463
24	S BalaM MarcosG SzaboEmerging role of microRNAs in liver diseasesWorld J Gastroenterol1556335640200910.3748/wjg.15.563319960558
25	S YoonTH KimA NatarajanAcute liver injury upregulates microRNA-491-5p in mice, and its overexpression sensitizes Hep G2 cells for tumour necrosis factor-alpha-induced apoptosisLiver Int30376387201010.1111/j.1478-3231.2009.02181.x20015148
26	AD SharmaN NarainEM HändelMicroRNA-221 Regulates FAS-Induced Fulminant Liver FailureHepatology5316511661201110.1002/hep.2424321400558
27	B MundtF KühnelL ZenderInvolvement of TRAIL and its receptors in viral hepatitisFASEB J179496200312475902
28	K StreetzL LeifeldD GrundmannTumor necrosis factor alpha in the pathogenesis of human and murine fulminant hepatic failureGastroenterology119446460200010.1053/gast.2000.936410930380
29	T Ben MosheH BarashTB KangRole of caspase-8 in hepatocyte response to infection and injury in miceHepatology4510141024200717385212
30	S LinX LiuR YinInhibitory effects of short hairpin RNA against caspase-8 on apoptosis of murine hepatoma Hepa1–6 cellsBiosci Trends35357200920103947
31	L ZenderS HutkerC LiedtkeCaspase 8 small interfering RNA prevents acute liver failure in miceProc Natl Acad Sci USA10077977802200310.1073/pnas.133092010012810955