MiR-132抑制肿瘤转移
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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

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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)


MiR-132 Inhibits Tumor Metastasis
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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

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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)

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    摘要:

    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.

    Abstract:

    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.

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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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  • 收稿日期:2012-05-15
  • 最后修改日期:2012-05-18
  • 接受日期:2012-05-18
  • 在线发布日期: 2013-02-26
  • 出版日期: 2013-02-20
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