miR-506-3p调控乳腺癌细胞增殖、凋亡以及其对多西他赛耐药性的作用机制
Mechanism of miR-506-3p regulating breast cancer cell proliferation,apoptosis and its resistance to docetaxel
张爱峰 1胡运轩 1韩江涛1
作者信息
- 1. 075000 张家口,张家口市妇幼保健院乳腺外科
- 折叠
摘要
目的 探讨miR-506-3p对乳腺癌细胞增殖、凋亡以及对多西他赛耐药性的影响及分子机制.方法 体外培养MCF-10A 细胞和乳腺癌细胞系 MDA-MB-231、MCF-7、T47D、BT549;在 MDA-MB-231 细胞中转染 miR-506-3p模拟物、TUBA1C小干扰RNA或TUBA1C过表达质粒、或共转染TUBA1C过表达质粒和miR-506-3p模拟物.实时荧光定量PCR(RT-qPCR)检测miR-506-3p和TUBA1CmRNA表达;四甲基偶氮唑盐比色法(MTT)检测细胞增殖及半数抑制浓度(IC50);流式细胞术检测细胞凋亡;双荧光素酶报告实验检测miR-506-3p和TUBA1C的靶向关系.结果 与MCF-10A细胞相比,MDA-MB-231、T47D和BT549细胞中 miR-506-3p表达降低,TUBA1C mRNA表达升高(P＜0.05).miR-506-3p高表达或TUBA1C 低表达后,MDA-MB-231细胞的活性降低,凋亡率升高,IC50值降低(P＜0.05)omiR-506-3p靶向调控TUBA1C,过表达TUBA1C逆转了miR-506-3p高表达对乳腺癌细胞MDA-MB-231增殖、凋亡以及对多西他赛耐药性的影响.结论 miR-506-3p高表达可能通过靶向下调TUBA1C抑制乳腺癌细胞增殖,促进细胞凋亡且减弱乳腺癌细胞对多西他赛的耐药性.
Abstract
Objective This study investigates the effect and molecular mechanism of miR-506-3p on breast cancer cell prolif-eration,apoptosis and its resistance to docetaxel.Methods MCF-10A cells and breast cancer cell lines MDA-MB-231,MCF-7,BT549 were cultured in vitro.In MDA-MB-231 cells,miR-506-3p mimics,TUBA1C small interfering RNA or TUBA1C overexpressing plasmid were transfected,or TUBA1C overexpressing plasmid and miR-506-3p mimics were co-transfected.Real-time fluorescent quantitative PCR(RT-qPCR)was used to detect the expression of miR-506-3p and TUBA1C mRNA;methyl thiazolyl tetrazolium as-say(MTT)was used to detect cell proliferation and half inhibitory concentration(IC50);flow cytometry was used to detect cell apopto-sis;dual luciferase reporter experiment was used to detect targeting relationship of miR-506-3p and TUBA1C.Results Compared with MCF-10A cells,the expression of miR-506-3p in MDA-MB-231,T47D and BT549 cells was decreased,and the expressions of TUBA1C mRNA and protein were increased(P＜0.05).After high expression of miR-506-3p or low expression of TUBA1C,the activity of MDA-MB-231 cells was decreased,apoptosis rate was increased,and IC50 value was decreased(P＜0.05).miR-506-3p targets and regulates TUBA1C;overexpression of TUBA1C reverses the effects of high expression of miR-506-3p on the proliferation and apoptosis of breast cancer cells MDA-MB-231 and the resistance to docetaxel.Conclusion The high expression of miR-506-3p may inhibit breast cancer cell proliferation,promote cell apoptosis and reduce the resistance of breast cancer cells to docetaxel by targeting and down-regulating TUBA1C.
关键词
miR-506-3p/TUBA1C/乳腺癌/增殖/凋亡/多西他赛/耐药性Key words
miR-506-3p/alpha-tubulin specific 1c chain/breast cancer/proliferation/apoptosis/docetax-el/drug resistance引用本文复制引用
出版年
2024
NETL
NSTL
万方数据