miR-139-5p修饰UC-MSC来源外泌体对乳腺癌细胞干性和放疗敏感性的影响  

Effects of miR-139-5p-modified UC-MSC-derived exosomes on stemness and radiotherapy sensitivity of breast cancer cells

作　　者：时彩艳 黄国定 李崇伟 刘峰 SHI Caiyan;HUANG Guoding;LI Chongwei;LIU Feng(Department of Oncology,Hainan Western Central Hospital,Danzhou 571700,China)

机构地区：[1]海南西部中心医院肿瘤内科,海南儋州571700

出　　处：《中国医科大学学报》2025年第3期251-256,共6页Journal of China Medical University

基　　金：海南省卫生健康行业科研基金(22A200157)。

摘　　要：目的探究miR-139-5p修饰的人脐带间充质干细胞(UC-MSC)来源的外泌体对乳腺癌细胞干性和放疗敏感性的影响。方法UC-MSC转染miR-139-5p模拟物和阴性对照后,提取外泌体并鉴定。将乳腺癌MCF-7细胞分为对照组、miR-NC Exo组、miR-139-5p Exo组,免疫荧光染色观察外泌体被细胞摄取情况,细胞肿瘤球形成实验检测肿瘤球形成数量,Western blotting检测细胞中干性相关蛋白Nanog、SOX2和OCT4的表达。将MCF-7细胞分为对照组、2 Gy X线组、miR-139-5p Exo组、miR-139-5p Exo+2 Gy X线组,MTT法检测细胞存活率,流式细胞术检测细胞凋亡率。结果成功分离到UC-MSC来源的外泌体,且转染miR-139-5p的UCMSC来源的外泌体中miR-139-5p相对表达量高于转染miR-NC的UC-MSC来源的外泌体(P<0.05),2种外泌体均能被MCF-7细胞摄取。与对照组、miR-NC Exo组比较,miR-139-5p Exo组MCF-7细胞肿瘤球形成数量减少,Nanog、SOX2和OCT4蛋白的相对表达水平下调(P<0.05)。与对照组比较,2 Gy X线组和miR-139-5p Exo组MCF-7细胞存活率下降,凋亡率升高(P<0.05);与2 Gy X线组比较,miR-139-5p Exo+2 Gy X线组MCF-7细胞存活率下降,凋亡率升高(P<0.05)。结论经miR-139-5p修饰的UC-MSC来源的外泌体能够抑制乳腺癌MCF-7细胞干性特征,并提高MCF-7细胞的放疗敏感性。Objective To investigate the effects of miR-139-5p-modified human umbilical cord mensenchymal stem cell(UC-MSC)-derived exosomes on stemness and radiotherapy sensitivity of breast cancer cells.Methods MCF-7 cells were divided into the control,miR-NC Exo,and miR-139-5p Exo groups.Immunofluorescence staining was used to observe the cellular uptake of exosomes.A tumor sphere formation assay determined the number of tumor spheres formed.Western blotting detected NANOG,SOX2,and OCT4 protein expression levels.MCF-7 cells were divided into control,2 Gy X ray,miR-139-5p Exo,and miR-139-5p Exo+2 Gy X ray groups.The survival rate of MCF-7 cells was detected by the MTT method.The apoptosis rate of MCF-7 cells was determined using flow cytometry.Results Compared to the control and miR-NC Exo groups,the number of tumor spheres formed by MCF-7 cells in the miR-139-5p Exo group was significantly decreased,and the relative expression levels of Nanog,SOX2,and OCT4 proteins were significantly downregulated(P<0.05).Compared to the control group,the survival rate of MCF-7 cells in the 2 Gy X ray and miR-139-5p Exo groups was significantly decreased,and the apoptosis rate was significantly increased(P<0.05).Compared to the 2 Gy X ray group,the survival rate of MCF-7 cells in the miR-139-5p Exo+2 Gy X ray group was significantly decreased,and the apoptosis rate was significantly increased(P<0.05).Conclusion UC-MSC-derived exosomes modified by miR-139-5p inhibit the stemness of MCF-7 cells and enhance the radiotherapy sensitivity of MCF-7 cells.

关 键 词：乳腺癌 miR-139-5p 外泌体 肿瘤细胞干性 放疗敏感性 

分 类 号：R737.9[医药卫生—肿瘤]