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The role of Lin28/let 7 pathway in Wilms' tumor

Lin28/let 7 通路在肾母细胞瘤中的作用

基本信息

批准号：
9355581
负责人：
Alena Yermalovich
金额：
$ 3.2万
依托单位：
HARVARD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-09-21 至 2018-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9355581
关键词：
Address Affect Alleles Binding Biogenesis Breast Cancer Biology Career Choice Cell physiology Cells Child Childhood Colon Communities Development Developmental Biology Diagnosis Disease Embryo Engineering Environment Equilibrium Exonuclease Family Gene Expression Genes Genetic Goals Hospitals Human Immunohistochemistry In Vitro Kidney Knock-out Laboratories Laboratory Research LacZ Genes Lead Learning Liver Maintenance Malignant Childhood Neoplasm Malignant Neoplasms Malignant childhood renal neoplasm Mentors Messenger RNA MicroRNAs Molecular Mus Mutation Nephroblastoma Neuroblastoma North America Pathogenesis Pathology Pathway interactions Pattern Perlman syndrome Phenocopy Play Positioning Attribute Prevention Property Proteins RNA RNA-Binding Proteins Reporter Genes Research Research Project Grants Role Stem cells Testing Therapeutic Training Translating Translational Research Tumor Suppressor Proteins Universities Vertebrates Work base cancer therapy conditional mutant embryo tissue exome sequencing insight interest leukemia loss of function mutation mouse model nephrogenesis novel nuclease outcome forecast overexpression paralogous gene post-doctoral training precursor cell professor progenitor research facility self-renewal tenure track transcriptome sequencing tumor tumorigenesis

项目摘要

Project Summary Lin28 is a highly conserved RNA binding protein that modifies gene expression via direct binding of mRNAs and by blocking the processing of the let-7 family of tumor suppressor microRNAs. In vertebrates, Lin28a and its paralog Lin28b are highly expressed in stem and progenitor cells of the early embryo, and play important roles in the balance of self-renewal, proliferation, and differentiation. Over-expression of Lin28 has been detected in a wide array of malignancies, including colon, breast, kidney, liver, leukemia, and several pediatric embryonal tumors such as Neuroblastoma and Wilms tumor (WT). Wilms tumor is the fourth most common type of childhood cancer and the most common type of pediatric kidney cancer, affecting 1 in 10,000 children in North America. WT is particularly interesting as it arises from multipotent embryonic kidney precursor cells that fail to differentiate, providing a window into the mechanisms of early renal development and potentially into the properties of embryonic kidney stem cells. The general goal of this dissertation project is to inform the molecular pathogenesis of Wilms tumor, and to interrogate the Lin28/let-7 pathway as an exemplar of the large variety of human tumors in which this pathway has been implicated.

项目摘要 Lin 28是一种高度保守的RNA结合蛋白，通过直接结合mRNA来修饰基因表达以及通过阻断肿瘤抑制microRNA的let-7家族的加工。在脊椎动物中，Lin 28 a和 Lin 28 b在早期胚胎干细胞和祖细胞中高表达，在胚胎发育中起重要作用。在自我更新、增殖和分化的平衡中发挥作用。Lin 28的过度表达已经被证实是一种基因突变。在多种恶性肿瘤中检测到，包括结肠癌、乳腺癌、肾癌、肝癌、白血病和几种儿科肿瘤。胚胎性肿瘤，如神经母细胞瘤和Wilms肿瘤（WT）。肾母细胞瘤是第四常见的一种儿童癌症，也是最常见的儿童肾癌，每10，000名儿童中就有1名患有这种癌症。在北美，WT特别令人感兴趣，因为它起源于多能胚胎肾前体细胞这为了解早期肾脏发育机制提供了一个窗口，并可能为研究肾脏发育机制提供了一个新的途径。胚胎肾干细胞的特性。本论文项目的总体目标是告知 Wilms肿瘤的分子发病机制，并询问Lin 28/let-7通路作为大的许多人类肿瘤都与这种途径有关。