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miR-129在乳腺癌中表达下调及其对乳腺癌细胞迁移运动的影响

王球玉, 唐珺, 周佽想, 赵倩

上海交通大学医学院/中国科学院上海生命研究院健康科学研究所，上海 200025；上海交通大学医学院病理生理学教研室，上海 200025

摘要

本文旨在寻找抑制乳腺癌转移的microRNA (miRNA)。综合利用miRNA靶基因预测软件和目前已知与肿瘤转移相关基因的对比分析，寻找出5个可能靶向乳腺癌转移相关基因的miRNA。以高转移乳腺癌细胞系MDA-MB-231细胞为模型，体外瞬时转染上述5个miRNA模拟物，用Transwell迁移实验筛选出能抑制细胞迁移运动的miRNA，并用Western blot检测分析了5个miRNA对E-cadherin蛋白表达的影响。筛选结果显示，miR-101、miR-129、miR-130、miR-133a和miR-144可以抑制乳腺癌细胞的迁移运动能力，其中miR101、miR129、miR-133a和miR144能不同程度地上调E-cadherin表达。划痕实验结果显示，miR-129能抑制其它两株高转移乳腺癌细胞系BT549和MDA-MB-435s的迁移运动。更为重要的是，Real-time RT-PCR结果显示，miR-129在大部分乳腺癌患者的癌组织样本和乳腺癌细胞系中表达下调。以上结果提示，过表达miR-129可以显著抑制乳腺癌细胞的迁移运动能力，而miR-129的低表达可能参与了乳腺癌的发生、发展和转移。

关键词： miR-129; 乳腺癌; 迁移

分类号：R329

[The down-regulation of miR-129 in breast cancer and its effect on breast cancer migration and motility.] [Article in Chinese]

WANG Qiu-Yu, TANG Jun, ZHOU Ci-Xiang, ZHAO Qian

Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine (SJTU-SM) &； Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS), Shanghai 200025, China； Department of Pathophysiology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China

Abstract

To search the microRNAs (miRNA) which suppress metastasis of breast cancer, we utilize three well known micoRNA target prediction programs, Targetscan, Pictar and miRanda, to select the microRNAs that target the genes related to tumor metastasis. We chose MDA-MB-231 with high metastasis ability as the model to evaluate the effect of miRNAs on cell motility through Transwell migration assay. After the first round of screening, miR-129 is found to significantly inhibit the migration of MDA-MB-231 both in Transwell migration assay and wound healing assay. Furthermore, miR-129 also shows great suppressive ability to cell mobility and migration in another two breast cancer cell lines BT549 and MDA-MB-435s. Most importantly, miR-129 is down-regulated both in breast cancer tissues compared with the paired adjacent normal breast tissues, and in breast cancer cell lines compared with normal breast epithelial cell MCF10A (P < 0.05). These results indicate that over-expression of miR-129 could inhibit breast cancer motility and migration, and the down-regulation of miR-129 may participate in the breast cancer migration and metastasis.

Key words: miR-129; breast cancer; migration

收稿日期：2012-05-05　　录用日期：2012-07-30

通讯作者：赵倩　　E-mail: qzhao@shsmu.edu.cn

引用本文：

王球玉, 唐珺, 周佽想, 赵倩. miR-129在乳腺癌中表达下调及其对乳腺癌细胞迁移运动的影响[J]. 生理学报 2012; 64 (4): 403-411.

WANG Qiu-Yu, TANG Jun, ZHOU Ci-Xiang, ZHAO Qian. [The down-regulation of miR-129 in breast cancer and its effect on breast cancer migration and motility.] [Article in Chinese] . Acta Physiol Sin 2012; 64 (4): 403-411 (in Chinese with English abstract).