miR-556-3p通过靶向结合DAB2IP抑制其表达在促进乳腺癌进展中的机制研究  

Study on the Mechanism of miR-556-3p Inhibiting Its Expression Through Targeted Binding to DAB2IP in Promoting Breast Cancer Progression

作　　者：曹秋影 李晶[1] 孙永敏[1] 吕春歌 CAO Qiuying;LI Jing;SUN Yongmin;LU Chunge(Nuclear Medicine Department,the Second Affiliated Hospital of Zhengzhou University,Zhengzhou 450000,China)

机构地区：[1]郑州大学第二附属医院核医学科,河南郑州450000

出　　处：《河南医学研究》2024年第22期4033-4038,共6页Henan Medical Research

摘　　要：目的研究miR-556-3p在乳腺癌的表达变化,阐明miR-556-3p通过靶向结合DAB2IP促进乳腺癌进展的机制。方法回顾性分析2018年1月至2019年5月郑州大学第二附属医院乳腺癌组织标本共计65例,同时纳入30例乳腺正常组织作为对照组,利用Real-time PCR检测miR-556-3p在乳腺癌组织和对照组以及乳腺癌细胞系中的表达变化规律;随访5 a,统计患者的生存率;体外实验中,利用MTT实验、transwell实验、荧光素酶报告基因以及细胞转染等方法检测miR-556-3p对乳腺癌细胞的活性、侵袭能力的影响。利用Western blot、Real-time PCR方法检测miR-556-3p对DAB2IP和MAPK通路的影响,对miR-556-3p与DAB2IP的靶向关系采用荧光素酶报告系统分析。结果miR-556-3p在乳腺癌患者组织中表达水平高于对照组,miR-556-3p高表达的乳腺癌患者的总生存率低于miR-556-3p低表达患者;体外实验中,miR-556-3p在乳腺癌细胞中的表达变化与乳腺癌细胞的细胞活力、侵袭呈正相关性;在MCF-10A、MCF-7细胞系中,过表达miR-556-3p后,细胞活力、侵袭增高,敲低miR-556-3p后,细胞活力、侵袭降低。DAB2IP的表达受miR-556-3p直接调控,过表达miR-556-3p后,乳腺癌细胞中DAB2IP、Erk、p-Erk的蛋白表达水平降低,敲低miR-556-3p后,以上蛋白水平增加。结论miR-556-3p靶向结合DAB2IP3’-UTR区域,从而阻滞DAB2IP mRNA翻译,促进MCF-10A、MCF-7细胞的增殖,miR-556-3p在促进乳腺癌发生与发展过程中起到关键性作用,为乳腺癌的靶向防治提供新的理论依据。Objective To investigate the expression of miR-556-3p in breast cancer and elucidate the mechanism by which miR-556-3p promotes the progression of breast cancer by targeting DAB2IP.Methods Retrospective analysis was made on 65 breast cancer tissue samples from January 2018 to May 2019 in the Second Affiliated Hospital of Zhengzhou University,and 30 normal breast tissues were included as the control group.Real-time PCR was used to detect the expression of miR-556-3p in breast cancer tissues,control groups and breast cancer cell lines.The patients were followed up for 5 years,and the survival rate of the patients was counted.In vitro experiments,MTT test,transwell test,luciferase reporter gene and cell transfection were used to detect the effect of miR-556-3p on the activity and invasion of breast cancer cells.Western blot and Real-time PCR methods were used to detect the effects of miR-556-3p on the DAB2IP and MAPK pathways.The targeting relationship between miR-556-3p and DAB2IP was analyzed using a luciferase reporter system.Results miR-556-3p expression levels in breast cancer patient tissues were higher than in control group samples.The overall survival rate of breast cancer patients with high miR-556-3p expression was lower than that of the low expression patients.In vitro experiments showed that changes in miR-556-3p expression in breast cancer cells were positively correlated with cell viability and invasion.In the MCF-10A and MCF-7 cell lines,overexpression of miR-556-3p increased cell viability and invasion,while knockdown of miR-556-3p decreased these parameters.The expression of DAB2IP was directly regulated by miR-556-3p,and after overexpression of miR-556-3p,the protein levels of DAB2IP,Erk,and p-Erk in breast cancer cells decreased,while knockdown of miR-556-3p led to an increase in these protein levels.Conclusion miR-556-3p targets the 3’-UTR region of DAB2IP,thereby blocking DAB2IP mRNA translation and promoting the proliferation of MCF-10A and MCF-7 cells.miR-556-3p plays a key role in the occur

关 键 词：乳腺癌 miR-556-3p DAB2IP 细胞增殖 MCF-10A细胞系 MAPK通路 

分 类 号：R737.9[医药卫生—肿瘤]