基础医学与临床 ›› 2023, Vol. 43 ›› Issue (1): 95-101.doi: 10.16352/j.issn.1001-6325.2023.01.0095

• 研究论文 • 上一篇    下一篇

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

杨良权1*, 于淼1, 姜茜1, 张明慧1, 杨海松2   

  1. 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
  • 收稿日期:2021-09-01 修回日期:2022-05-18 发布日期:2022-12-27
  • 通讯作者: *ylquan4tb@aliyun.com
  • 基金资助:
    秦皇岛市重点研发计划科技支撑项目(202005A028)

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

YANG Liangquan1*, YU Miao1, JIANG Qian1, ZHANG Minghui1, YANG Haisong2   

  1. 1. Department of Galactophore Surgery, Maternal & Child Care Center of Qinhuangdao, Qinhuangdao 066000;
    2. Department of Galactophore Surgery, the Affiliated Hospital of Guizhou Medical University, Guiyang 550004, China
  • Received:2021-09-01 Revised:2022-05-18 Published:2022-12-27
  • Contact: *ylquan4tb@aliyun.com

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。

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

Abstract: 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.

Key words: breast cancer, miR-504, proteasome activator complex subunit 3, MCF-7 cell, proliferation

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