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  

The down-regulation of miR-129 in breast cancer and its effect on breast cancer migration and motility

作　　者：王球玉[1] 唐珺[1] 周佽想[2] 赵倩[2] 

机构地区：[1]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 [2]上海交通大学医学院病理生理学教研室,上海200025

出　　处：《生理学报》2012年第4期403-411,共9页Acta Physiologica Sinica

基　　金：supported by the National Natural Science Foundation of China (No. 81172521 and 81170505)

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。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 MCF 10A （P 〈 0.05）. These results indicate that over-expression of miR-129 could inhibit breast cancer motility and migration, and the down-regulation ofmiR-129 may participate in the breast cancer migration and metastasis.

关 键 词：miR-129 乳腺癌 迁移 

分 类 号：R737.9[医药卫生—肿瘤]