Let-7 通过转录因子E2F1调控鼻咽癌ALDH1+细胞干细胞性质的研究

项目名称： Let-7 通过转录因子E2F1调控鼻咽癌ALDH1+细胞干细胞性质的研究

项目编号： No.81201672

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： 吴爱兵

作者单位： 广东医学院

项目金额： 23万元

中文摘要： 近年来鼻咽癌的放化疗等治疗手段有了明显的提高，但是仍有部分鼻咽癌患者治疗后出现复发和转移，导致这种结果的主要原因可能是鼻咽癌干细胞的持续存在。前期研究表明，ALDH1可作为鼻咽癌干细胞鉴定和分选的标记物，并可作为鼻咽癌患者临床预后的指标。同时我们发现Let-7能调控鼻咽癌ALDH1+细胞干细胞性质，但是具体的机制不清楚。前期研究还发现，Let-7与转录因子E2F1存在调控关系，而E2F1是PI3K/Akt、pRB-E2F1信号通路的重要基因，是否Let-7通过E2F1介导PI3K/Akt、pRB-E2F1信号通路来调控ALDH1+细胞的干细胞性质。为证实这个假说；采用染色质免疫共沉淀技术确定E2F1是否直接调控Let-7，并检测PI3K/Akt，pRb-E2F1信号通路蛋白的表达。如果该项目能顺利实施，将为阐明调控鼻咽癌干细胞性质的分子机制提供理论基础。

中文关键词： Let-7；肿瘤干细胞；乙醛脱氢酶1；转录因子E2F1；鼻咽癌

英文摘要： Although advances in radiation and chemotherapy have improved the prognosis of individuals with NPC, many patients still recur because of therapeutic resistance and distant metastasis. This result may be due to the role of cancer stem cells (CSCs). Previous studies showed that ALDH1 can be a functional maker of identification and screening of NPC stem cell, also be used as indicators of clinical prognosis of patients with nasopharyngeal carcinoma. Our studies have found that let-7 can rugulate prosperities of ALDH1+cells, but the molecular mechanism is not clear. Previous works have found that transcriptional factor E2F1 might regulate let-7, which whether regulate the ALDH1+cells stem cell properties through E2F1 mediated by PI3K/Akt,pRB-E2F1 pathways. In order to demonstrate our hypothesis, chromatin immunoprecipitation assay(Chip) technology to determine whether the let-7 is to regulated directly by E2F1. Subsequently,elevated let-7a in ALDH1+cells and analyzed proteins expression of PI3K / Akt, pRb-E2F1 signal pathway by western blot.If the project is successfully implemented, we will clarify to maintain of of a new idea of the molecular mechanism of nasopharyngeal carcinoma stem cells, and may provide a new experimental theoretical basis for invasion, metastasis and treatment resistance of nasopharyngeal c

英文关键词： Let-7；Cancer stem cell；Aldehyde dehydrogenase 1;；Transcriptional factor E2F1；Nasopharyngeal carcinoma