miR-93-5p对三阴性乳腺癌放疗敏感性的影响及其机制探讨  

Effect of miR-93-5p on radiosensitivity of triple-negative breast cancer and its mechanism

作　　者：高慧 潘驰 倪清涛 徐红 GAO Hui;PAN Chi;NI Qingtao;XU Hong(Southeast University Hospital,Jiangsu Nanjing 210009,China;The Affiliated Taizhou People's Hospital of Nanjing Medical University,Taizhou School of Clinical Medicine,Nanjing Medical University,Jiangsu Taizhou 225300,China)

机构地区：[1]东南大学医院,江苏南京210009 [2]南京医科大学附属泰州人民医院,南京医科大学泰州临床医学院,江苏泰州225300

出　　处：《现代肿瘤医学》2025年第1期14-19,共6页Journal of Modern Oncology

基　　金：江苏省双创博士项目(编号:202003205,202003206);南京医科大学泰州临床医学院科研项目-国自然(青年基金)培育专项(编号:TZKY20220105,TZKY20220109)。

摘　　要：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。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 detected 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 pathology.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.

关 键 词：三阴性乳腺癌 miR-93-5p 放疗敏感性 GSDME 

分 类 号：R737.9[医药卫生—肿瘤]