Let-7c通过阻断雌激素激活的Wnt信号通路活性而抑制乳腺癌干细胞的自我更新能力  

Let-7c suppresses the activity of estrogen induced Wnt signaling and represses the self-renewal ability of breast cancer stem cells

作　　者：魏辉[1] 张勇[2] 江静[1] 贾奇[1] 罗璐[1] 侯俊明[1] 任宏[3] 

机构地区：[1]陕西中医药大学附属医院肿瘤四科,陕西咸阳712000 [2]宝鸡市中医医院胸外科,陕西宝鸡721000 [3]西安交通大学医学院第一附属医院胸部肿瘤外科,胸外二科,陕西西安710061

出　　处：《现代肿瘤医学》2016年第21期3349-3355,共7页Journal of Modern Oncology

基　　金：国家自然科学基金资助项目(编号:81272418)

摘　　要：目的:探究Let-7c是否能通过Wnt信号通路调控乳腺癌干细胞自我更新能力。方法:分析乳腺癌临床样本中Let-7家族成员的表达情况,检测Let-7与ERα的相关性,进一步探讨Let-7c与Wnt通路活性分子表达的相关性;在细胞试验中,通过ALDH流式细胞仪分选法及微成球实验分选乳腺癌干细胞;采用免疫印迹、荧光素酶报告试验及免疫荧光实验,验证Let-7c与ERα-3'UTR是否能直接结合。结果:Let-7家族成员在乳腺癌组织中高表达,并且Let-7b和Let-7c的表达与患者临床预后显著相关;Let-7c表达与ERα表达呈负相关,Let-7c表达与Wnt信号通路活性分子呈负相关;Let-7c能够抑制雌激素受体阳性乳腺癌干细胞自我更新能力;Let-7c能够直接结合到ERα-3'UTR上,进而抑制ERα的表达和雌激素激活的Wnt信号通路。结论:我们的研究首次证实了Let-7c通过抑制雌激素激活的Wnt通路活性,而对肿瘤干细胞的自我更新能力产生抑制作用。ObjectiveTo study the effects of Let -7 on Wnt signaling pathway in breast cancer stem cells. Methpds：We first checked the expression levels of Let -7 family in clinical tissues,and then detected the correlation be-tween Let -7c and ERa expression. Further,the relationship among Let -7c and Wnt signaling was examined in clin-ical tissues. Through Western blot,luc - assay and immunofluorescence staining,we then explored the roles of Let -7c in breast cancer stem cells （BCSCs） ,and tested whether Let -7 can directly regulate the expression of ERa and Wnt signal. Using Lentivirus - mediated RNA interference technology,we detected that whether regulated ERa . Results：We found that higher expression levels of Let -7b and Let -7c indicate better clinical prognosis（P 〈0. 01） . Further, we found that only Let -7c was inversely correlated with ERa expression. Besides, Let -7c repressed estrogen in-duced self - renewal of stem cells. We confirmed that Let -7 decreased ERa by degrading the mRNA,and also, en-forced Let -7c inhibited the activity of estrogen induction of Wnt signaling pathway. Conclusion ： Let - 7 c inhibited estrogen induced Wnt activity through decreasing ERa expression level.

关 键 词：Let-7miRNAs 乳腺癌 乳腺癌干细胞 雌激素受体 WNT信号通路 

分 类 号：R737.9[医药卫生—肿瘤]