Racial Disparity of microRNA in Hepatitis C Virus Mediated Hepatocellularcarcinoma

丙型肝炎病毒介导的肝细胞癌中 microRNA 的种族差异

• 批准号: 8872288
• 负责人: Ratna B. Ray
• 金额: $ 21.25万
• 依托单位: SAINT LOUIS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-04-01 至 2017-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8872288
• 关键词: Address; African American; Area; Biological Markers; Biopsy Specimen; Caucasians; Chronic Hepatitis C; Data; Death Rate; Development; Disease Progression; Ethnic group; Genetic; Goals; Growth; Hepatitis C; Hepatitis C Incidence; Hepatitis C virus; Hepatocyte; Human; Laboratory Finding; Liver diseases; Malignant neoplasm of liver; Mediating; Medical; MicroRNAs; Modality; Molecular; Patients; Play; Primary carcinoma of the liver cells; Process; Race; Regulation; Research; Research Proposals; Risk Factors; Role; Serum; Staging; Therapeutic; Up-Regulation; Virus; caucasian American; cell growth; circulating microRNA; cohort; innovation; interest; liver biopsy; loss of function; public health relevance; racial disparity

 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.

 描述（由适用提供）：乙型肝炎病毒（HCV）介导的末期肝病，包括肝细胞癌（HCC），是非洲裔美国人（AAS）的日益严重的问题。该项目的核心目标是研究HCV介导的肝癌的种族差异。 AA患者的HCV感染介导的死亡率比Ca高约2倍。关于慢性感染族群中肝病进展的潜在机制的信息很少。我们的研究建议将检查AA中HCV介导的终末期肝病的以前出乎意料的领域。 microRNA（miRNA）在多步细胞生长调节过程中起关键作用，而慢性HCV感染与miRNA表达之间的关系是对理解病毒介导的疾病进展的考虑。我们的初步数据表明，与Ca相比，在慢性感染的AA血清中调节了一组MicroRNA。我们假设这些电路miRNA可能是对HCV感染的AA患者的HCC发育的潜在预测生物标志物，并且涉及消除肝细胞生长的管制。这是对HCC的预测生物标志物以及种族差异的基本分子机制的鉴定将具有很大的转化益处。我们的长期目标是将这些发现从实验室转化为识别预测生物​​标志物的床边，并为HCV介导的肝脏疾病进展而开发治疗方式。影响：该R21探索性建议的结果将通过研究miRNA作为低估种族差异的遗传因素的作用，从而产生很大的影响。我们的研究将解释为什么与高加索人相比，非洲裔美国人发生的HCV介导的肝癌事件更高。