A pleiotropically acting microRNA, miR-31, inhibits breast cancer metastasis.
A pleiotropically acting microRNA, miR-31, inhibits breast cancer metastasis
Valastyan S, Reinhardt F, Benaich N et al.
Cell, 2009, 137, 1032-1046
Since the most devastating consequences of cancer arise from the process of metastatic dissemination, elucidation and evaluation of the biology of the process by which cancer cells invade locally, intravasate into the circulation and extravasate and survive in the distant tissues, is of fundamental importance. Work to date has focused mainly on cell-to-cell contact functions and the influences of the metastatic host tissue site but our understanding of the process is still rudimentary. The present paper presents, in a set of elegant experiments, the possible role of specific microRNAs (miRNAs) in this process for the first time. miRNAs are small RNAs that suppress gene expression in a post-transcriptional fashion acting via the untranslated regions of cognate mRNA targets. More than 650 miRNAs have been identified but in the present study one, designated miR-31, was found to be specifically attenuated in aggressive human breast cancer cells (MDA-MB-231) by more than 100fold compared to non-metastatic tumour cells (e.g. HMLER, MCF-7-Ras). Stable expression of miR-31 in metastatic MDA-MB-231 cells reduced invasion and motility by 10-20-fold--and when injected into the mammary fat pad of mice, the resultant tumours remained well encapsulated and non-invasive.
Furthermore, when such transfected cells were injected into the mouse circulation via the tail vein, such miR-31-expressing 231 cells generated 40-fold fewer lung metastases compared to controls. Further experiments to inhibit miR-31 using miRNA sponges showed that suppression of miR-31 enhanced invasion of non-metastatic MCF7-Ras cells and enhanced metastases to the lungs; the effects of miR-31 in repressing metastasis-promoting genes including RhoA indicates that miR-31 uses multiple mechanisms to suppress metastasis.
Interestingly, in human breast tissues, basal-like breast cancers exhibited 40% reduced expression of miR-31 compared to grade-matched ER-positive tumours. Thus miR-31's ability to prevent metastasis may prove a useful clinical finding especially in the context of basal-like breast cancer where therapeutic strategies are currently limited.
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|Publication:||Advances in Breast Cancer|
|Date:||Sep 1, 2009|
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