Data from Concurrent Suppression of Integrin α<sub>5</sub>, Radixin, and RhoA Phenocopies the Effects of miR-31 on Metastasis

Abstract

<div>Abstract<p>miR-31 inhibits breast cancer metastasis via the pleiotropic suppression of a cohort of prometastatic target genes that include <i>integrin α<sub>5</sub></i> (<i>ITGA5</i>), <i>radixin</i> (<i>RDX</i>), and <i>RhoA</i>. We previously showed that the concomitant overexpression of ITGA5, RDX, and RhoA was capable of overriding the antimetastatic effects of ectopically expressed miR-31 <i>in vivo</i>. However, these prior studies failed to investigate whether the combined suppression of the endogenous mRNAs encoding these three proteins recapitulated the <i>in vivo</i> consequences of miR-31 expression on metastasis. We show here that short hairpin RNA–mediated concurrent downregulation of ITGA5, RDX, and RhoA is sufficient to phenocopy the full spectrum of described influences of miR-31 on metastasis <i>in vivo</i>, including the effects of this microRNA (miRNA) on local invasion, early post-intravasation events, and metastatic colonization. These findings provide mechanistic insights into the metastatic process and have implications about the importance of pleiotropy for the biological actions of miRNAs. Cancer Res; 70(12); 5147–54. ©2010 AACR.</p></div>