目的:探讨miR-93-5p对三阴性乳腺癌(triple-negative breast cancer,TNBC)放疗敏感性的影响,并探讨其相关机制.方法:双荧光素酶实验发现GSDME(Gasdermin E)是miR-93-5p的靶基因;构建miR-93-5p稳定过表达细胞,小鼠皮下成瘤后行放射治疗;采用实时荧光定量PCR(real-time fluorescence quantitative PCR,qPCR)及蛋白质印迹(Western Blot,WB)方法检测各组GSDME的表达.检测TNBC肿瘤患者癌组织及癌旁组织中miR-93-5p及GSDME的表达,比较其在癌组织及癌旁组织中的差异表达变化,分析其与TNBC临床病理的关联.结果:miR-93-5p直接靶向GSDME 3'-UTR,过表达miR-93-5p小鼠的组织中GSDME低表达.放疗促进GSDME表达,并且阻断miR-93-5p对GSDME的抑制.miR-93-5p在细胞中主要定位于细胞质.GSDME在TNBC患者肿瘤组织中较癌旁组织中减少.结论:放疗促进TNBC中GSDME表达,并且阻断miR-93-5p对GSDME的抑制,miR-93-5p有作为放射生物学标志物的潜力.
Effect of miR-93-5p on radiosensitivity of triple-negative breast cancer and its mech-anism
Objective:To explore the effect of miR-93-5p on the radiosensitivity of triple-negative breast cancer(TNBC)and its related mechanism.Methods:Double luciferase experiment showed that GSDME(Gasdermin E)was the target gene of miR-93-5p.Stable overexpression cells of miR-93-5p were constructed,and mice were treated with radiotherapy after subcutaneous tumor formation.The expression of GSDME in each group was detec-ted by real-time fluorescence quantitative PCR(qPCR)and Western Blot(WB).To detect the expression of miR-93-5p and GSDME in cancer tissues and adjacent tissues of TNBC tumor patients,compare their differential expression changes in cancer tissues and adjacent tissues,and analyze their correlation with TNBC clinical patholo-gy.Results:miR-93-5p directly targets GSDME 3'-UTR,and the expression of GSDME was low in the tissues of mice overexpressing miR-93-5p.Radiotherapy promoted the expression of GSDME and blocked the inhibition of miR-93-5p on GSDME.miR-93-5p was mainly located in cytoplasm.GSDME was decreased in tumor tissue of TNBC patients compared with that in adjacent tissues.Conclusion:Radiotherapy promotes GSDME expression and blocks the inhibition of GSDME by miR-93-5p,which has potential as a radiobiological marker.
triple-negative breast cancermiR-93-5pradiosensitivityGSDME
万方数据
维普
