Racial Disparity of microRNA in Hepatitis C Virus Mediated Hepatocellularcarcinoma

 描述（由申请人提供）：丙型肝炎病毒（HCV）介导的终末期肝病，包括肝细胞癌（HCC），是非洲裔美国人（AA）中日益严重的问题。该项目的中心目标是调查HCV介导的肝癌的种族差异。HCV感染介导的AA患者死亡率比CA高约2倍。关于慢性HCV感染种族人群中肝病进展的潜在机制的信息非常少。我们的研究计划将探讨这一以前未探索的领域丙型肝炎介导的终末期肝病之间的AA。microRNA（miRNAs）在多步骤细胞生长调节过程中起关键作用，慢性HCV感染与miRNAs表达之间的关系在理解病毒介导的疾病进展中具有相当大的意义。我们的初步数据表明，与CA相比，在慢性HCV感染的AA血清中调节了一组microRNA。我们假设这些循环中的miRNAs可能是HCV感染的AA患者中HCC发展的潜在预测生物标志物，并参与肝细胞生长的失调。因此，鉴定HCC的预测性生物标志物和种族差异的潜在分子机制将具有巨大的转化益处。我们的长期目标是将这些发现从实验室转移到床边，识别预测生物标志物，并开发HCV介导的肝病进展的治疗方式。影响：这项R21探索性提案的结果将通过研究miRNAs作为遗传因素对种族差异的影响产生重大影响。我们的研究将解释为什么非洲裔美国人与白人相比，HCV介导的肝癌发病率更高。

 DESCRIPTION (provided by applicant): Hepatitis C virus (HCV) mediated end stage liver disease, including hepatocellular carcinoma (HCC), is a growing problem among African Americans (AAs). The central goal of this project is to investigate the racial disparity of HCV mediated liver cancer. HCV infection mediated death rate among AA patients is about 2- fold higher than CA. Very little information is available about the underlying mechanisms of liver disease progression among chronically HCV infected ethnic groups. Our research proposal will examine this previously unexplored area of HCV mediated end stage liver disease among AA. microRNAs (miRNAs) play critical roles in multi-step cell growth regulatory processes, and the relationship between chronic HCV infection and miRNA expression is of considerable interest in understanding virus mediated disease progression. Our preliminary data indicated a group of microRNAs modulated in chronically HCV infected AA sera as compared to that of CA. We hypothesize that these circulatory miRNAs can be potential predictive biomarker towards HCC development in HCV infected AA patients, and are involved deregulating hepatocyte growth. Thus, identification of predictive biomarkers for HCC and the underlying molecular mechanisms for race disparity will have a great translational benefit. Our long term objectives are to translae these findings from the laboratory to the bedside identifying predictive biomarker, and developing therapeutic modalities for HCV mediated liver disease progression. Impact: The results from this R21 exploratory proposal will have a high impact by investigating the role of miRNAs as genetic factors for understating racial disparity. Our research will explain why African Americans have higher incidence of HCV mediated liver cancer as compared to Caucasians.