研究人员发现，一种名为miR-9的小RNA（miRNA）控制着乳腺肿瘤的扩散和发展，新成果发表在2月在线出版的《自然—细胞生物学》期刊上。新发现认为，未来miR-9也许可以成为治疗乳腺癌的潜在靶标。

以前的研究指出，小RNA或者会激活肿瘤，或者会抑制肿瘤的扩散。Robert Weinberg和同事发现，在小鼠体内，通过调节黏附蛋白质E-cadherin，由致癌基因Myc直接控制的miR-9会让小鼠体内的乳腺细胞具有侵入性。miR-9也增强了血管的生长，从而增加了肿瘤的血液供应。因为在患恶性乳腺癌患者的初期，其miR-9的水平在升高，因此，这一通道对人类来说可能也至关重要。

在本期一篇相关的新闻评论中，Greg Goodall讨论了miR-9对其他类型肿瘤的重要性，包括神经母细胞瘤，以及它在正常发育过程中的作用。

Nature Cell Biology 21 February 2010 | doi:10.1038/ncb2024

miR-9, a MYC/MYCN-activated microRNA, regulates E-cadherin and cancer metastasis

Li Ma1,2, Jennifer Young1,7, Harsha Prabhala3,7, Elizabeth Pan1, Pieter Mestdagh4, Daniel Muth5, Julie Teruya-Feldstein6, Ferenc Reinhardt1, Tamer T. Onder1,2, Scott Valastyan1,2, Frank Westermann5, Frank Speleman4, Jo Vandesompele4 & Robert A. Weinberg1,2

MicroRNAs (miRNAs) are increasingly implicated in regulating the malignant progression of cancer. Here we show that miR-9, which is upregulated in breast cancer cells, directly targets CDH1, the E-cadherin-encoding messenger RNA, leading to increased cell motility and invasiveness. miR-9-mediated E-cadherin downregulation results in the activation of β-catenin signalling, which contributes to upregulated expression of the gene encoding vascular endothelial growth factor (VEGF); this leads, in turn, to increased tumour angiogenesis. Overexpression of miR-9 in otherwise non-metastatic breast tumour cells enables these cells to form pulmonary micrometastases in mice. Conversely, inhibiting miR-9 by using a 'miRNA sponge' in highly malignant cells inhibits metastasis formation. Expression of miR-9 is activated by MYC and MYCN, both of which directly bind to the mir-9-3 locus. Significantly, in human cancers, miR-9 levels correlate with MYCN amplification, tumour grade and metastatic status. These findings uncover a regulatory and signalling pathway involving a metastasis-promoting miRNA that is predicted to directly target expression of the key metastasis-suppressing protein E-cadherin.

1 Whitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA.
2 Massachusetts Institute of Technology Ludwig Center for Molecular Oncology, Cambridge, Massachusetts 02142, USA.
3 Medical Scientist Training Program, University of Virginia, Charlottesville, Virginia 22908, USA
4 Center for Medical Genetics, Ghent University Hospital, 9000 Ghent, Belgium.
5 Department of Tumor Genetics, German Cancer Center, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
6 Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
7 These authors contributed equally to this work.