miR-196调控p27表达对乳腺癌细胞内分泌治疗耐药的影响  

Effect of miR-196 on endocrine therapy for breast cancer by targeting p27

作　　者：孟然 余岳 曹旭晨 Meng Ran, Yu Yue, Cao Xuchen(The First Department of Breast Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clini- col Research Center for Cancer, Tianjin 300060, China. Key Laboratory of Cancer Prevention and Therapy, Tian- fin 300060, China, Tianjin＇s Clinical Research Center for Cancer, Tianjin 300060, China. Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education, Tianjin 300060, China)

机构地区：[1]天津医科大学肿瘤医院乳腺一科,国家肿瘤临床医学研究中心,天津市肿瘤防治重点实验室,教育部乳腺癌防治重点实验室,300060

出　　处：《中华内分泌外科杂志》2017年第6期504-508,共5页Chinese Journal of Endocrine Surgery

基　　金：国家自然科学基金（81372843）

摘　　要：目的探讨miR-196表达水平对乳腺癌内分泌治疗敏感性的影响，初步揭示其潜在的分子机制。方法通过实时荧光定量PCR（RT-qPCR）检测ER＋乳腺癌细胞系MCF7和ER．乳腺癌细胞系BT549中miR-196表达水平。在MCF7细胞系中外源转染miR-196后，通过MTr和克隆形成评价miR-196表达水平对tamoxifen敏感性的影响。采用双荧光素酶报告实验、RT-qPCR和Westernblot确定miR-196对p27的调控作用。结果miR-196在BT549中呈高表达，在MCF7中呈低表达。TAM作用后较对照组相比。miR-196过表达的MCF7细胞的细胞活力和克隆形成能力都显著提高。过表达miR-196能显著降低p273’-UTR活性和表达水平。p27过表达能消除miR-196所导致的TAM内分泌耐药。结论miR-196能通过调控其靶基因p27表达，诱导乳腺癌细胞内分泌治疗抵抗。Objective To determine the effect of miR-196 on sensitivity of endocrine therapy for breast cancer and to explore its possible molecular mechanism. Methods The expression of miR-196 was detected by real-time quantitative PCR （RT-qPCR） in MCF7 （ER＋） and BT549 （ER-）. The sensitivity of tamoxifen on MCF7 cells was evaluated by MTI＂ and colony formation. Dual-luciferase, RT-qPCR and western blot assays were used to determine the regulation of miR-196 on p27. Results The expression of miR-196 was up-regulated in BT549 compared to that in MCF7 cells. The cell viability and colony formation were increased in miR-196-overexpressed MCF7 cells compared to those in the control ceils after treatment with tamoxifen. The luciferase activity and ex- pression of p27 were decreased in miR-196-overexpressed MCF7 cells compared to those in the control cells. Overexpression of p27 eliminated the effect of miR-196-induced endocrine therapy resistance in MCF7 cell. Con- clusion miR-196 promotes breast cancer endocrine resistance by targeting p27.

关 键 词：乳腺癌 内分泌治疗 miR-196 P27 

分 类 号：R737.9[医药卫生—肿瘤]