Abstract：
:miR-31 inhibits breast cancer metastasis via the pleiotropic suppression of a cohort of prometastatic target genes that include integrin alpha(5) (ITGA5), radixin (RDX), and RhoA. We previously showed that the concomitant overexpression of ITGA5, RDX, and RhoA was capable of overriding the antimetastatic effects of ectopically expressed miR-31 in vivo. However, these prior studies failed to investigate whether the combined suppression of the endogenous mRNAs encoding these three proteins recapitulated the in vivo 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 in vivo, 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.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Valastyan S,Chang A,Benaich N,Reinhardt F,Weinberg RAdoi
10.1158/0008-5472.CAN-10-0410subject
Has Abstractpub_date
2010-06-15 00:00:00pages
5147-54issue
12eissn
0008-5472issn
1538-7445pii
0008-5472.CAN-10-0410journal_volume
70pub_type
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