4.7 Article Retracted Publication

被撤回的出版物: Concomitant suppression of three target genes can explain the impact of a microRNA on metastasis (Retracted article. See vol. 29, pg. 686, 2015)

Journal

GENES & DEVELOPMENT
Volume 23, Issue 22, Pages 2592-2597

Publisher

COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gad.1832709

Keywords

MicroRNA; metastasis; miR-31; breast cancer; colonization; pleiotropy

Funding

  1. NIH [RO1 CA078461]
  2. MIT Ludwig Center for Molecular Oncology
  3. U. S. Department of Defense
  4. Breast Cancer Research Foundation
  5. DoD BCRP Idea Award
  6. American Cancer Society Research
  7. Daniel K. Ludwig Foundation

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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-alpha 5, 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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