miR-34a通过Notch1信号通路对肺癌干细胞的抑制.doc

miR-34a通过Notch1信号通路对肺癌干细胞的抑制 韩纪昌，张祎捷，李红兵，杨存葆，马超楠，戚冠斌(河南大学淮河医院呼吸内科，河南省开封市 475000) 引用本文：韩纪昌，张祎捷，李红兵，杨存葆，马超楠，戚冠斌. miR-34a通过Notch1信号通路对肺癌干细胞的抑制[J].中国组织工程研究，2016，20(23):3349-3356. DOI: 10.3969/j.issn.2095-4344.2016.23.001 ORCID: 0000-0001-8450-019X(张祎捷) 文章快速阅读： 文题释义： 微小RNA：microRNA(miRNA)是一类内源性非编码单链小分子RNA，长度一般为18-25个核苷酸。成熟的微小RNA可以与靶mRNA的3’端非翻译区特异性结合，促使靶蛋白mRNA降解或抑制其翻译，最终使内源基因表达得到调控。miRNA广泛参与细胞的增殖、分化、凋亡等过程的调节，几乎所有恶性肿瘤发生过程中都存在miRNA的异常表达。 Notch信号通路Inhibitory effect of miR-34a on lung cancer stem cells via Notch1 signaling pathway Han Ji-chang, Zhang Yi-jie, Li Hong-bing, Yang Cun-bao, Ma Chao-nan, Qi Guan-bin (Department of Respiratory Medicine, Huaihe Hospital of Henan University, Kaifeng 475000, Henan Province, China) Abstract BACKGROUND: It has been proved that miR-34a plays an inhibitory role in the growth of lung cancer stem cells, but the underlying mechanism remains unclear. OBJECTIVE: To explore the inhibitory effect of miR-34a on lung cancer stem cells and the underlying mechanism. METHODS: The CD133+ lung cancer stem cells were separated from lung cancer A549 cell lines using magnetic activated cell sorting method. And miR-34a-overexpressing CD133+ lung cancer stem cells were established by liposome transfection technology. Besides, the targeted relationship between miR-34a and Notch1 was analyzed by the dual-luciferase reporter. Afterwards, Notch1 silencing was performed by gene knockout, and its effect on lung cancer stem cells was determined. RESULTS AND CONCLUSION: After sorted and detected by immunomagetic selection and flow cytometry assay respectively, a high rate of CD133+ lung cancer stem cell was obtained. And qRT-PCR detected that the expression level of miR-34a in CD133+ lung cancer stem cells was significantly lower than that in CD133- lung cancer stem cells. Moreover, miR-34a-overexpressing CD133+ lung cancer stem cells were successfully constructed and miR-34a significantly inhibited proliferation and induced apoptosis of lung cancer ste