In vivo characterization of microRNA regulation

microRNA 调控的体内表征

• 批准号: 7915227
• 负责人: JESSE R ZAMUDIO
• 金额: $ 4.76万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-29 至 2012-09-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7915227
• 关键词: Affect; Animals; Cancer Model; Cell Culture Techniques; Cell Proliferation; Development; Engineering; Fluorometry; Gene Expression; Gene Expression Regulation; Goals; Growth; Human; Imagery; Imaging Techniques; Knock-in Mouse; Life; Link; Lymphoproliferative Disorders; Malignant Neoplasms; Measures; Mediating; MicroRNAs; Microscopy; Monitor; Mus; Pathogenesis; Play; RNA; Regulation; Reporter; Repression; Research; Role; Small RNA; System; Testing; Tissues; Transgenes; Transgenic Mice; Translational Repression; base; cell transformation; cell type; embryonic stem cell; enhanced green fluorescent protein; in vivo; insight; protein expression; public health relevance; tumor; tumor progression; tumorigenesis

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.

描述（由申请人提供）：癌症发病机理基于异常增殖 细胞。 microRNA（miRNA）是小的RNA分子，通过靶向调节基因表达 mRNA用于翻译和/或降解的mRNA，并参与人类肿瘤。 最近的研究表明，miRNA的翻译抑制受细胞增殖状态的影响。 为了进一步发展miRNA介导的基因调节的基本理解，并揭示了影响 在miRNA调节上的异常细胞增殖，转基因小鼠将用A设计 用于miRNA调控的生物发光报告基因转基因。体内miRNA翻译 抑制水平将在不同的细胞增殖状态下进行量化，并与稳定相关 miRNA细胞浓度。将进行全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法。通过越过miRNA报告基因转基因 小鼠具有各种用于肿瘤和淋巴增生性疾病的癌症模型，异常的影响 将监测对miRNA调节的增殖，以测试它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节RNA分子 并与癌症形成有关。为了促进我们对MicroRNA调节的理解，我们 将开发一种用于测量正常和患病中miRNA介导的翻译抑制的系统 组织。目标是洞悉体内miRNA调节并衡量的贡献 通过缺陷的miRNA调控，癌症发展进展的异常生长。