miR⁃504调控蛋白酶体激活因子抑制人乳腺癌细胞系MCF⁃7增殖及迁移  

miR-504 regulates proteasome activator and inhibits the proliferation and migration of breast cancer cell line MCF-7

作　　者：杨良权 于淼 姜茜 张明慧 杨海松 YANG Liangquan;YU Miao;JIANG Qian;ZHANG Minghui;YANG Haisong(Department of Galactophore Surgery,Maternal&Child Care Center of Qinhuangdao,Qinhuangdao 066000;Department of Galactophore Surgery,the Affiliated Hospital of Guizhou Medical University,Guiyang 550004,China)

机构地区：[1]秦皇岛市妇幼保健院乳腺外科,河北秦皇岛066000 [2]贵州医科大学附属医院乳腺外科,贵州贵阳550004

出　　处：《基础医学与临床》2023年第1期95-101,共7页Basic and Clinical Medicine

基　　金：秦皇岛市重点研发计划科技支撑项目(202005A028)。

摘　　要：目的观察miR-504在模型裸鼠以及乳腺癌细胞生物学行为的调节作用,寻找miR-504在调控过程中的关键靶基因,探究miR-504在乳腺癌中的调控机制。方法构建乳腺癌模型小鼠并观察miR-504对瘤体生长的影响。TargetScan筛选miR-504的靶基因并通过双荧光素酶报告基因实验证实;RT-qPCR、Western blot检测蛋白酶体激活因子复合体亚基3(PSME3)在乳腺癌组织和癌旁组织中的表达;CCK8法、流式细胞测量术和Transwell小室法检测miR-504和PSME3对人乳腺癌细胞系MCF-7细胞增殖,周期和迁移能力的作用。结果在乳腺癌裸鼠移植瘤模型中miR-504能抑制瘤体生长;PSME3是miR-504的靶基因,在乳腺癌组织的表达明显升高(P<0.01),上调miR-504的表达能抑制PSME3的表达(P<0.01);较NC组,miR-504 mimic组能抑制乳腺癌细胞增殖、S期阻滞和迁移能力,而较miR-504 mimic组,miR-504 mimic+PSME3组MCF-7细胞增殖、S期比例和迁移能力升高(P<0.01)。结论miR-504可能通过靶向调控PSME3在乳腺癌中发挥抑癌作用。Objective To observe the regulation of miR-504 in mouse models and the biological behavior of breast cancer cells,find the key target genes of miR-504 in the regulation process,and explore the working mechanism of miR-504 in breast cancer.Methods A mouse model of breast cancer was established and the effect of miR-504 on tumor growth was observed.Target genes of miR-504 were screened by Target Scaning and confirmed by double luciferase reporter gene assay.RT-qPCR and Western blot were used to detect proteasome activator complex subunit 3(PSME3)expression in breast cancer and adjacent tissues.The effects of miR-504 and PSME3 on proliferation,cycle and migration of human breast cancer cell line MCF-7 were determined by CCK8 assay,flow cytometry and Transwell assay.Results It was found that miR-504 inhibited tumor growth in nude mouse xenograft model of breast cancer(P<0.01).PSME3 was a target gene of miR-504,and its expression in breast cancer tissues was significantly increased.Up-regulation of miR-504 expression could inhibit the expression of PSME3(P<0.01).Compared with NC group,miR-504 mimic group could inhibit the proliferation,S-phase arrest and migration ability of breast cancer cells,while compared with miR-504 mimic group,miR-504 mimic+PSME3 group,increased proliferation the proportion of S-phase and migration ability(P<0.01)in MCF-7 cell.Conclusions miR-504 may play an anti-cancer role in breast cancer by targeting PSME3 regulation.

关 键 词：乳腺癌 miR-504 蛋白酶体激活因子复合体亚基3 MCF-7细胞 增殖 

分 类 号：R73-37[医药卫生—肿瘤]