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Concomitant suppression of three target genes can explain the impact of a microRNA on metastasis Export

Genes & Development (29 October 2009)

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cancer function mirna target

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10.1101/gad.1832709 It remains unclear whether a microRNA (miRNA) affects a given phenotype via concomitant down-regulation of its entire repertoire of targets or instead by suppression of only a modest subset of effectors. We demonstrate that inhibition of breast cancer metastasis by miR-31âa miRNA predicted to modulate >200 mRNAsâcan be entirely explained by miR-31's pleiotropic regulation of three targets. Thus, concurrent re-expression of integrin-α5, radixin, and RhoA abrogates miR-31-imposed metastasis suppression. These effectors influence distinct steps of the metastatic process. Our findings have implications concerning the importance of pleiotropy for the biological actions of miRNAs and provide mechanistic insights into metastasis.


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