A Pleiotropically Acting Microrna, Mir-31, Inhibits Breast Cancer Metastasis Accessed Terms of Use Detailed Terms a Pleiotropically Acting Microrna, Mir-31, Inhibits Breast Cancer Metastasis
A Pleiotropically Acting Microrna, Mir-31, Inhibits Breast Cancer Metastasis Accessed Terms of Use Detailed Terms a Pleiotropically Acting Microrna, Mir-31, Inhibits Breast Cancer Metastasis
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3.2
通讯作者：
Citation Valastyan;Ferenc Scott;Nathan Reinhardt;Diana Benaich;Attila M Calogrias;Zhigang C Szász
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作者：
Citation Valastyan;Ferenc Scott;Nathan Reinhardt;Diana Benaich;Attila M Calogrias;Zhigang C Szász
文章根据出版商的政策提供，可能受美国版权法的约束。请参阅出版商的网站了解使用条款。麻省理工学院已公开发表了这篇文章。请分享此访问对您有何益处。你的故事很重要。MicroRNA非常适合调节肿瘤转移，因为它们能够协调抑制许多靶基因，从而可能使它们能够在侵袭-转移级联的多个步骤中进行干预。我们确定了一个micro-RNA例证这些属性，miR-31，其表达与人类乳腺癌患者的转移呈负相关。miR-31在其他侵袭性乳腺肿瘤细胞中的过表达抑制转移我们部署了一种稳定的micro-RNA海绵策略来抑制体内miR-31;这使得其他非侵袭性乳腺癌细胞转移。这些表型不涉及对原发性肿瘤发展的混杂影响，并且特别归因于miR-31介导的对转移的几个步骤的抑制，包括局部侵袭、外渗或在远端部位的初始存活以及转移性定殖。这种多效性是通过协调抑制一组促进转移的基因，包括RhoA。事实上，RhoA再表达部分逆转了miR-31施加的转移抑制。这些发现表明miR-31使用多种机制来对抗转移。有关本文的视频摘要，请参阅在线补充数据中提供的Paper-Flick文件。
Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. The MIT Faculty has made this article openly available. Please share how this access benefits you. Your story matters. SUMMARY MicroRNAs are well suited to regulate tumor metas-tasis because of their capacity to coordinately repress numerous target genes, thereby potentially enabling their intervention at multiple steps of the invasion-metastasis cascade. We identify a micro-RNA exemplifying these attributes, miR-31, whose expression correlates inversely with metastasis in human breast cancer patients. Overexpression of miR-31 in otherwise-aggressive breast tumor cells suppresses metastasis. We deploy a stable micro-RNA sponge strategy to inhibit miR-31 in vivo; this allows otherwise-nonaggressive breast cancer cells to metastasize. These phenotypes do not involve confounding influences on primary tumor development and are specifically attributable to miR-31-mediated inhibition of several steps of metastasis, including local invasion, extravasation or initial survival at a distant site, and metastatic colonization. Such pleiotropy is achieved via coordinate repression of a cohort of metastasis-promoting genes, including RhoA. Indeed, RhoA re-expression partially reverses miR-31-imposed metastasis suppression. These findings indicate that miR-31 uses multiple mechanisms to oppose metastasis. For a video summary of this article, see the Paper-Flick file available with the online Supplemental Data.