miR-155-5p增强卵巢癌细胞UWB1.289对PARP抑制剂的敏感性  

miR-155-5p Enhances the Sensitivity of Ovarian Cancer Cell UWB1.289 to PARP Inhibitors

作　　者：盛辰晨 何乐伟 王充 张春晓 杨诗敏 席晓薇[1] SHENG Chen-chen;HE Le-wei;WANG Chong;ZHANG Chun-xiao;YANG Shi-min;XI Xiao-wei(Department of Obstetrics and Gynecology,Shanghai General Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai,200080,China)

机构地区：[1]上海交通大学附属第一人民医院妇产科,上海200080

出　　处：《现代生物医学进展》2022年第18期3420-3427,共8页Progress in Modern Biomedicine

基　　金：国家自然科学基金项目(81772767)。

摘　　要：目的:探讨卵巢癌细胞UWB1.289中miR-155-5p对PARP抑制剂敏感性的影响及可能涉及的分子机制研究。方法:采用qRT-PCR技术检测miR-155-5p在有BRCA1/2突变和无BRCA1/2突变的卵巢癌组织及卵巢癌细胞中的表达情况。利用细胞转染、qRT-PCR以及Western Blot技术检测转染miR-155-5p模拟物和抑制剂的卵巢癌细胞UWB1.289中miR-155-5p的表达以及同源重组修复相关基因SIRT1、BRG1的表达。通过双荧光素酶报告基因实验验证miR-155-5p与SIRT1、BRG1之间的靶向性。运用CCK-8检测卵巢癌细胞UWB1.289中miR-155-5p对PARP抑制剂敏感性的影响。结果:与无BRCA1/2突变的卵巢癌组织及卵巢癌细胞相比,miR-155-5p在有BRCA1/2突变的卵巢癌组织及卵巢癌细胞中低表达。转染miR-155-5p模拟物可增加卵巢癌细胞UWB1.289中miR-155-5p的表达,同时降低同源重组修复相关基因SIRT1、BRG1的表达;转染miR-155-5p抑制剂可下调卵巢癌细胞UWB1.289中miR-155-5p的表达,同时增加SIRT1、BRG1的表达,进一步通过双荧光素酶报告基因实验证实miR-155-5p与SIRT1、BRG1存在特异性靶向结合序列。与对照组相比,干扰同源重组修复相关基因以及miR-155-5p过表达均可增强卵巢癌细胞UWB1.289对PARP抑制剂的敏感性。结论:miR-155-5p可能通过影响同源重组修复基因增强卵巢癌细胞UWB1.289对PARP抑制剂的敏感性。Objective:To investigate the effect of miR-155-5p on the sensitivity of ovarian cancer cell UWB1.289 to PARP inhibitors,and to explore the possible molecular mechanism.Methods:qRT-PCR was used to detect the expression of miR-155-5p in BRCA1/2-mutated and non-BRCA1/2-mutated ovarian cancer tissues and ovarian cancer cells.Cell transfection,qRT-PCR and Western Blot techniques were used to detect the expression levels of miR-155-5p,as well as homologous recombination repair-related genes SIRT1 and BRG1 in ovarian cancer cell UWB1.289,which were transfected with miR-155-5p mimics or miR-155-5p inhibitor.The targeting of miR-155-5p to SIRT1 and BRG1 were verified by dual-luciferase reporter gene assay.The effect of miR-155-5p on the sensitivity of PARP inhibitors in ovarian cancer cell UWB1.289 was detected by CCK-8.Results:Compared with ovarian cancer tissues and ovarian cancer cells without BRCA1/2 mutation,miR-155-5p was lowly expressed in ovarian cancer tissues and cells with BRCA1/2 mutation.Transfection of miR-155-5p mimics could increase the expression of miR-155-5p in ovarian cancer cell UWB1.289,while reducing the expression of homologous recombination repair-related genes SIRT1 and BRG1;transfection of miR-155-5p inhibitor could down-regulate the expression of miR-155-5p in ovarian cancer cell UWB1.289,while increasing the expression of SIRT1 and BRG1.Further,the dual-luciferase reporter gene assay confirmed that miR-155-5p had specific targeted binding sequences to SIRT1 and BRG1.Compared with the control group,interfering with genes related to homologous recombination repair could enhance the sensitivity of ovarian cancer cell UWB1.289 to PARP inhibitors,and overexpression of miR-155-5p could also enhance the sensitivity of ovarian cancer cell UWB1.289 to PARP inhibitors.Conclusions:miR-155-5p could enhance the sensitivity of ovarian cancer cell UWB1.289 to PARP inhibitors by affecting homologous recombination repair genes.

关 键 词：miR-155-5p 卵巢癌 PARP抑制剂 敏感性 同源重组修复 

分 类 号：R-33[医药卫生] R737.31