一种针对 Dicer 的 microRNA 用于转移控制。

A MicroRNA targeting dicer for metastasis control.

机构信息

Department of Histology, Microbiology and Medical Biotechnologies, University of Padua School of Medicine, viale Colombo 3, 35126 Padua, Italy.

出版信息

Cell. 2010 Jun 25;141(7):1195-207. doi: 10.1016/j.cell.2010.05.017.

Abstract

Although specific microRNAs (miRNAs) can be upregulated in cancer, global miRNA downregulation is a common trait of human malignancies. The mechanisms of this phenomenon and the advantages it affords remain poorly understood. Here we identify a microRNA family, miR-103/107, that attenuates miRNA biosynthesis by targeting Dicer, a key component of the miRNA processing machinery. In human breast cancer, high levels of miR-103/107 are associated with metastasis and poor outcome. Functionally, miR-103/107 confer migratory capacities in vitro and empower metastatic dissemination of otherwise nonaggressive cells in vivo. Inhibition of miR-103/107 opposes migration and metastasis of malignant cells. At the cellular level, a key event fostered by miR-103/107 is induction of epithelial-to-mesenchymal transition (EMT), attained by downregulating miR-200 levels. These findings suggest a new pathway by which Dicer inhibition drifts epithelial cancer toward a less-differentiated, mesenchymal fate to foster metastasis.

摘要

虽然特定的 microRNAs (miRNAs) 在癌症中可以上调,但全球 miRNA 下调是人类恶性肿瘤的共同特征。这种现象的机制及其带来的优势仍知之甚少。在这里,我们鉴定了一个 microRNA 家族,miR-103/107,它通过靶向 Dicer(miRNA 加工机制的关键组成部分)来减弱 miRNA 的生物合成。在人类乳腺癌中,高水平的 miR-103/107 与转移和不良预后相关。在功能上,miR-103/107 在体外赋予迁移能力,并使体内原本非侵袭性细胞具有转移性扩散能力。抑制 miR-103/107 可抵抗恶性细胞的迁移和转移。在细胞水平上,miR-103/107 促进的一个关键事件是通过下调 miR-200 水平诱导上皮-间充质转化 (EMT)。这些发现表明,Dicer 抑制使上皮性癌症向分化程度较低的间质命运漂移,从而促进转移的新途径。

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