Concomitant suppression of three target genes can explain the impact of a microRNA on metastasis.
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-31-a miRNA predicted to modulate >200 mRNAs-can be entirely explained by miR-31's pleiotropic regulation of three targets. Thus, concurrent re-expression of integrin-alpha5, 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.
Valastyan
Scott
S
Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA.
Benaich
Nathan
N
Chang
Amelia
A
Reinhardt
Ferenc
F
Weinberg
Robert A
RA
D000818:Animals; D001943:Breast Neoplasms / Q000503:physiopathology*; D018270:Carcinoma, Ductal, Breast / Q000503:physiopathology*; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism*; D009362:Neoplasm Metastasis / Q000503:physiopathology*
C534612:MIRN31 microRNA, human; D035683:MicroRNAs