Let-7在促结肠癌干细胞分化以及化疗敏感性中的作用研究

项目名称： Let-7在促结肠癌干细胞分化以及化疗敏感性中的作用研究

项目编号： No.81201688

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 肿瘤学1

项目作者： 宁宁

作者单位： 北京大学

项目金额： 24万元

中文摘要： 结肠癌是最常见的消化道恶性肿瘤之一，近些年我国结肠癌的发病率死亡率逐年增加，其病死原因多为肿瘤的复发和转移。随着肿瘤干细胞概念的提出以及该领域研究的深入，肿瘤干细胞的存在被认为是肿瘤复发和转移的主要原因，然而目前的治疗方法不能有效根除肿瘤干细胞，因此，针对肿瘤干细胞的治疗方法将会成为攻克肿瘤的重要手段。近年来的研究发现，在真核生物中广泛存在的小分子RNA参与包括细胞分化在内的几乎所有生物学功能以及包括肿瘤在内的多种疾病的发生和发展。大量研究表明小分子RNA let-7具有促进细胞分化的功能，然而在包括结肠癌在内的多种肿瘤中表达下降甚至缺失，最新的研究发现let-7在肿瘤干细胞中表达也明显下降。本课题拟通过增加let-7在结肠癌干细胞中的表达而促进结肠癌干细胞的分化，增强肿瘤干细胞对化疗药物的敏感性，从而抑制肿瘤的复发和转移，最终达到根治肿瘤的目的。

中文关键词： 结肠癌；肿瘤干细胞；分化；小RNA；Let-7

英文摘要： Colon cancer is one of the most common gastrointestinal malignancies, in recent years, the morbidity and mortality of colon cancer in China increases every year, and the cause of death for colon cancer patient mostly due to tumor recurrence and metastasis. With in-depth understanding of cancer stem cells, it was believed that the existence of cancer stem cells in the tumor is the major reason for tumor recurrence and metastasis, however, current therapies can not effectively eradicate cancer stem cells, therefore, a treatment with targeting the tumor stem cells will become an important means to overcome tumor. Recent studies have demonstrated that microRNAs, a type of small non-coding RNA widely expressed in eukaryotes, were involved in the regulation of most cellular functions, such as differentiation, and the aberrant expression of microRNAs has been implicated in numerous diseases, including tumors. Numerous studies have shown that let-7 has the function to promote cell differentiation, while its expression was usually decreased or absent in a variety of tumors, including colon cancer, the latest study revealed that the expression of let-7 in tumor stem cells also decreased significantly. This study aims to find a novel mean to inhibit the recurrence and metastasis of colon cancer through enforcing let-7 exp

英文关键词： colon cancer；cancer stem cells；differentiation；Micro-RNA；Let-7