研究人員發(fā)現(xiàn),，一種名為miR-9的小RNA（miRNA）控制著乳腺腫瘤的擴散和發(fā)展，新成果發(fā)表在2月在線出版的《自然—細胞生物學》期刊上,。新發(fā)現(xiàn)認為,，未來miR-9也許可以成為治療乳腺癌的潛在靶標。
以前的研究指出,，小RNA或者會激活腫瘤,，或者會抑制腫瘤的擴散。Robert Weinberg和同事發(fā)現(xiàn),，在小鼠體內(nèi),，通過調(diào)節(jié)黏附蛋白質(zhì)E-cadherin，由致癌基因Myc直接控制的miR-9會讓小鼠體內(nèi)的乳腺細胞具有侵入性,。miR-9也增強了血管的生長,，從而增加了腫瘤的血液供應(yīng)。因為在患惡性乳腺癌患者的初期,，其miR-9的水平在升高,，因此，這一通道對人類來說可能也至關(guān)重要,。
在本期一篇相關(guān)的新聞評論中,，Greg Goodall討論了miR-9對其他類型腫瘤的重要性，包括神經(jīng)母細胞瘤,，以及它在正常發(fā)育過程中的作用,。（生物谷Bioon.com）
更多乳腺癌研究：
Nature Medicine：乳腺癌治療藥物阻抑基因
Cell：不同乳腺癌干細胞分子特征對腫瘤發(fā)展趨勢的影響
Nature：與乳腺癌腫瘤形成和轉(zhuǎn)移有關(guān)的兩種miRNA
Cancer Research：二甲雙胍可抑制乳腺癌擴散
Cell：發(fā)現(xiàn)乳腺癌新型藥物靶標
生物谷推薦原始出處：
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.
