A Pleiotropically Acting MicroRNA, MiR-31, Inhibits Breast Cancer Metastasis

Overview

Journal Cell

Publisher Cell Press

Specialty Cell Biology

Date 2009 Jun 16

PMID 19524507

Citations 441

Authors

Scott Valastyan

Ferenc Reinhardt

Nathan Benaich

Diana Calogrias

Attila M Szasz

Zhigang C Wang

Jane E Brock

Andrea L Richardson

Robert A Weinberg

Affiliations

Soon will be listed here.

Abstract

MicroRNAs are well suited to regulate tumor metastasis 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 microRNA 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 microRNA 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.

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