In vivo characterization of microRNA regulation

描述（由申请人提供）：癌症发病机制是基于异常增殖 信元microRNAs（miRNAs）是一类通过靶向调控基因表达的小分子RNA分子， mRNA用于翻译抑制和/或降解，并参与人肿瘤发生。 最近的研究表明，miRNA的翻译抑制受到细胞增殖状态的影响。 进一步加深对miRNA介导的基因调控的基本认识， 异常细胞增殖对miRNA调控的影响，转基因小鼠将被工程化， 靶向miRNA调控的生物发光报告基因转基因。体内miRNAs的翻译 抑制水平将在不同的细胞增殖状态下定量，并与稳定的细胞增殖状态相关联。 miRNA细胞浓度。将进行整体动物研究和组织特异性定量 使用非侵入性荧光显微镜和荧光测定法。通过将miRNA报告基因转基因 小鼠用各种癌症模型进行肿瘤和淋巴增生性疾病的研究， 将监测增殖对miRNA调控的影响，以测试其如何有助于癌症进展。 公共卫生相关性：MicroRNA是控制基因表达的小调控RNA分子 并与癌症的形成有关。为了进一步了解microRNA的调控，我们 将开发一个系统，用于测量正常和疾病中miRNA介导的翻译抑制， 组织.目标是深入了解体内miRNA的调控，并测量 通过有缺陷的miRNA调节在癌症发展中的异常生长。

DESCRIPTION (provided by applicant): Cancer pathogenesis is based on the abnormal proliferation of cells. MicroRNAs (miRNAs) are small RNA molecules regulating gene expression by targeting mRNAs for translational repression and/or degradation and are involved in human oncogenesis. Recent studies show translational repression by miRNAs is influenced by cellular proliferation states. To further progress the basic understanding of miRNA-mediated gene regulation and reveal the affects of abnormal cellular proliferation on miRNA-regulation, transgenic mice will be engineered with a bioluminescent reporter transgene targeted for miRNA regulation. The in vivo miRNAs translational repression levels will be quantified in different cellular proliferative states and correlated to stable miRNA cellular concentration. Whole animal studies and tissue-specific quantification will be performed using non-invasive fluorescent microscopy and fluorometry. By crossing the miRNA reporter transgenic mouse with various cancer models for tumor and lymphoproliferative disorders, the affect of abnormal proliferation on miRNA regulation will be monitored to test how it may contribute to cancer progression. Public Health Relevance: MicroRNAs are small regulatory RNA molecules controlling gene expression and have been linked to cancer formation. To advance our understanding of microRNA regulation, we will develop a system for measuring miRNA-mediated translational repression in normal and diseased tissue. The goals are to gain insight into in vivo miRNA regulation and measure the contribution of abnormal growth in progressing cancer development through defective miRNA regulation.