| セッション情報 |
Hepatitis C i)Hepatitis C and HCC(I)
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| タイトル |
IF4c-1 MicroRNA Expression in Liver Tissue of Chronic Hepatitis and Hepatocellular Carcinoma
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| 演者 |
Masao Honda（Department of GastroenterologyKanazawa University Graduate School of MedicineJapan） |
| 共同演者 |
Shuichi Kaneko（Department of GastroenterologyKanazawa University Graduate School of MedicineJapan） |
| 抄録 |
MicroRNA（血RNA）plays an important role in the pathology of various diseases including infection andcancer． Using real－time polymerase chain reactionwe measured the expression of 188 miRNAs in liver tis－sues obtained from 12 patients with hepatitis B virus （HBV） 一related hepatocellu／1ar carcinoma （HCC） and14 patients with hepatitis C virus （HCV） 一related HCCincluding background liver tissues and normal liver（N） tissues obtained from 9 patients． Global gene expression in the same tissues was analyzed by cDNAmicroarray to examine whether the differentially expressed miRNAs could regulate their target genes．Detailed analysis of the differentially expressed miRNA revealed 2 types of miRNAone associated withHBV and HCV infections （19 miRNAs）the other with the stage of liver disease （31 mi’RNAs）． Pathwayanalysis of targeted genes using infection－associated miRNAs revealed that． the pathways related to celldeathDNA damagerecombination and signal transduction were activated in HBV infecte d liverandthose related to immune responseantigen presentatioq cell cycleproteasome and lipid metabolism wereactivated in HCV infected liver． The differences in the expression of infection－assoeiated miRNAs in theliver correlate d significantly with those observed in Hul L 7．5 cells in which infectious HBV or HCV clonesreplicated． O ut of the 31 miRNAs associated with disea＄e state17 were・ down－regulated in HCC which up－regulated cancer associated pathways such as cell cycleadhesionproteolysistranscription and transla－tionand 6 miRNAs were up－regulated in HCC which down－regulated anti－tumor immune response． Wevalidated functional relevance of these miRNAs using cell lines and experimenta’1 moue modeL We foundone miRNA was significantly associated with lipid accumulation and replication of HCV． We also found aunique miRNA that was related with the progression of hepatic fibrosis．ThusmiRNAs are important me－diators of HrBV and HCV infections as well as liver disease progressionand therefore could be potentialtherapeutic target molecules． |
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