miR-23a通过调控DNA错配修复蛋白MLH1、MSH2对子宫内膜样癌进展的影响及机制研究  

The effect and mechanism of miR-23a on the progress of endometrioid carcinoma by regulating DNA mismatch repair proteins MLH1 and MSH2

作　　者：韩雯[1] 王琲[1] 张怡 邵明昱[1] 杨宇星 刘浩楠 王春[1] HAN Wen;WANG Bei;ZHANG Yi;SHAO Mingyu;YANG Yuxing;LIU Haonan;WANG Chun(Department of Pathology,People's Hospital of Xinjiang Uygur Autonomous Region,Urumqi,Xinjiang 830001,China)

机构地区：[1]新疆维吾尔自治区人民医院病理科,新疆乌鲁木齐830001

出　　处：《中国优生与遗传杂志》2023年第5期895-900,共6页Chinese Journal of Birth Health & Heredity

基　　金：新疆维吾尔自治区自然科学基金项目(2022D01C157)。

摘　　要：目的 探讨微小RNA-23a(miR-23a)在子宫内膜样癌细胞进展中的作用及其可能的分子机制。方法 RT-qPCR实验和免疫组织化学染色分别检测子宫内膜样癌组和癌旁组织中miR-23a、Mut L同源物1(MLH1)和MutS蛋白同系物2(MSH2)的mRNA和蛋白表达。体外培养人子宫内膜样癌细胞株Ishikawa细胞,将细胞分为正常组、miR-23a inhibitor转染组以及miR-23a mimic转染组,RT-qPCR实验检测Ishikawa细胞中miR-23a、MLH1和MSH2的mRNA水平,CCK-8法检测细胞增殖能力,Transwell实验检测细胞迁移和侵袭能力,Western blot检测细胞中MLH1、MSH2蛋白的表达。结果 子宫内膜样癌组织中miR-23a相对表达水平较癌旁组织显著升高,MLH1和MSH2 mRNA和蛋白表达水平较癌旁组织显著降低(P<0.05)。miR-23 ainhibitor转染组Ishikawa细胞中miR-23a的表达、细胞增殖、迁移和侵袭能力较正常组均显著降低(P<0.05),miR-23a inhibitor转染组Ishikawa细胞中MLH1、MSH2的mRNA与蛋白水平较正常组均显著升高(P<0.05)。miR-23 amimic转染组Ishikawa细胞中miR-23a的表达、细胞增殖、迁移和侵袭能力较正常组均显著升高(P<0.05),miR-23a mimic转染组Ishikawa细胞中MLH1、MSH2的mRNA和蛋白水平较正常组均显著降低(P<0.05)。结论 miR-23a可能通过调控MLH1、MSH2的表达促进子宫内膜样癌细胞的增殖、迁移和侵袭能力。Objective To investigate the role of miR-23a in the progression of endometrial cancer cells and its possible molecular mechanism.Methods RT-qPCR and immunohistochemical staining were used to detect the mRNA and protein expression of miR-23a,Mut L homolog 1(MLH1)and MutS protein homolog 2(MSH2)in endometrioid carcinoma and adjacent tissues,respectively.Human endometrial cancer cell line Ishikawa was cultured in vitro,and the cells were divided into normal group,miR-23a inhibitor group and miR-23a mimic group.RT-qPCR was used to detect the expression of miR-23a,MLH1 and MSH2 mRNA in Ishikawa cells.CCK-8 assay was used to detect cell proliferation.Transwell assay was used to detect cell migration and invasion.Western blot was used to detect the expression of MLH1 and MSH2 proteins in the cells.Results The relative expression levels of miR-23a in endometrial cancer tissues were significantly higher than those in adjacent tissues,and the expression levels of MLH1 and MSH2 mRNA and protein were significantly lower than those in adjacent tissues(P<0.05).The expression of miR-23a and the ability of cell proliferation,migration and invasion in miR-23a inhibitor group were significantly lower than those in normal group(P<0.05).The mRNA and protein levels of MLH1 and MSH2 in miR-23a inhibitor group were significantly higher than those in normal group(P<0.05).The expression of miR-23a and the ability of cell proliferation,migration and invasion in miR-23a mimic group were significantly higher than those in normal group(P<0.05).The mRNA and protein levels of MLHI and MSH2 in miR-23a mimic group were significantly lower than those in normal group(P<0.05).Conclusion miR-23a may promote the proliferation,migration and invasion of endometrial cancer cells by regulating the expression of MLHl and MSH2.

关 键 词：miR-23a 子宫内膜样癌 侵袭 迁移 DNA错配修复蛋白 

分 类 号：R737.33[医药卫生—肿瘤]