MiR-132抑制肿瘤转移

MiR-132 Inhibits Tumor Metastasis

肿瘤转移是造成癌症难以根治的重要原因之一.近年来越来越多的研究发现,miRNA在肿瘤转移过程中发挥了直接或间接的作用.本研究的目标是找到一种特异性的肿瘤转移相关miRNA,能够作为抑制肿瘤转移的潜在靶标.miR-132是一类与炎症、血管生长、中枢神经系统相关的miRNA,至今还没有研究证明其与肿瘤转移相关.为了验证miR-132与肿瘤迁移的相关性,本研究将miR-132转染入高迁移乳腺癌细胞系MDA-MB-231细胞中,检测细胞迁移率的变化.实验发现miR-132能够抑制MDA-MB-231细胞的迁移.为了进一步揭示miR-132抑制细胞迁移的可能机制,本研究通过生物信息学手段寻找并鉴定了3种可能与肿瘤转移相关的miR-132的靶基因,它们分别是CHIP(STUB1)、G3BP1、G3BP2.分别比对MCF7与MDA-MB-231细胞,及转染miR-132和对照组MDA-MB-231细胞中以上3种基因的表达差异,我们发现G3BP1、G3BP2可能参与miR-132对肿瘤转移的调控.本研究首次报道miR-132与肿瘤转移的关系,并揭示了miR-132调节肿瘤转移的可能机制,说明了miR-132具有作为特异性抑制肿瘤转移靶标的潜力,为抑制肿瘤转移提供一个新的靶点.

It has been shown that some miRNAs are related with tumor invasion and metastasis directly or indirectly.Our aim is to find a specific miRNA which plays an essential role in tumor metastasis.Although it has been shown that miR-132 was associated with blood vessel growth,neural development and differentiation,and inflammation,relationship between miR-132 and tumor metastasis was not studied in any research.In order to identify the effect of miR-132 on tumor metastasis,the migration ability in vitro was detected on breast cancer cell line MDA-MB-231 cells transducted with miR-132（miR-132 group） and or mock miRNA（control group） by transwell assay.The results demonstrated significantly lower migration ratio in miR-132 case compared to that in control case,indicating inhibition effects on cancer migration of miR-132.To clarify the inhibition mechanism by which miR-132 inhibits cancer metastasis,target genes of miR-132 were screened and identified.They are CHIP（STUB1）,G3BP1 and G3BP2.The expression levels of these 3 genes in MCF7 cells（metastasis cell line） and MDA-MB-231 cells with or without transduction of miR-132 or mock miRNA were detected by PCR and Real-time PCR.Two key genes,G3BP1/G3BP2,were founded to be involved in the regulation of miR-132 to tumor metastasis,demonstrating that miR-132 could silence G3BP1/G3BP2,which resulted in the suppression of tumor metastasis.Our research suggests that miR-132 may be an important potential target used for inhibition of cancer metastasis and clinical therapy of cancer,and shed light on the suppression mechanisms of miR-132.