The role of CMTR2 in Lung Cancer

项目摘要 LIN28是一种高度保守的RNA结合蛋白，通过直接结合mRNAs来调节基因表达 并通过阻断LET-7肿瘤抑制基因家族的处理。在脊椎动物中，Lin28a和 它的伴系Lin28b在早期胚胎的干细胞和祖细胞中高表达，并发挥重要作用 在自我更新、增殖和分化的平衡中的作用。Lin28基因的过度表达 在广泛的恶性肿瘤中发现，包括结肠癌、乳腺癌、肾脏、肝脏、白血病和几个儿科 胚胎性肿瘤，如神经母细胞瘤和肾母细胞瘤。肾母细胞瘤是最常见的第四种肿瘤 儿童癌症类型和最常见的儿童肾癌类型，每10,000名儿童中就有1名儿童受到影响 在北美，WT特别有趣，因为它来自多潜能的胚胎肾脏前体细胞 未能区分，为了解早期肾脏发育的机制提供了一个窗口，并有可能进入 胚胎肾干细胞的特性。本论文项目的总体目标是告知 肾母细胞瘤的分子发病机制，并以大鼠为例探讨Lin28/let-7通路 与此途径有关的多种人类肿瘤。

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.