中国科学院生物物理研究所,中国科学院生物物理研究所,中国科学院研究生院,北京军区总医院,中国科学院生物物理研究所,北京军区总医院
国家自然科学基金资助项目(30871250),国家“十二五”科技重大专项(2011ZX09401-012)
Institute of Biophysics, The Chinese Academy of Sciences,Institute of Biophysics, Chinese Academiy of Sciences;Graduate School of The Chinese Academy of Sciences,Beijing Military General Hospital,Institute of Biophysics, The Chinese Academy of Sciences;Beijing Military General Hospital
This work was supported by grants from The National Natural Science Foundation of China (30871250), and The National Major Science and Technology Project in The Twelfth Five- Year Plan Period (2011ZX09401-012)
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.
管娣,刘春颖,陈晨,殷勤伟. MiR-132抑制肿瘤转移[J].生物化学与生物物理进展,2013,40(2):159-164
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