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Proc Natl Acad Sci U S A. 2011 Jan 11;108(2):522-7. doi: 10.1073/pnas.1017346108. Epub 2010 Dec 27.

miR-29 and miR-30 regulate B-Myb expression during cellular senescence.

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Department of Genetics, Yale School of Medicine, P.O. Box 208005, New Haven, CT 06520, USA.


Cellular senescence is a form of irreversible growth arrest and a major tumor suppressor mechanism. We show here that the miR-29 and miR-30 microRNA families are up-regulated during induced and replicative senescence and that up-regulation requires activation of the Rb pathway. Expression of a reporter construct containing the 3'UTR of the B-Myb oncogene is repressed during senescence, and repression is blocked by mutations in conserved miR-29 and miR-30 binding sites in the B-Myb 3'UTR. In proliferating cells, transfection of miR-29 and miR-30 represses a reporter construct containing the wild-type but not the mutant B-Myb 3'UTR, and repression of the mutant 3'UTR is reinstituted by compensatory mutations in miR-29 and miR-30 that restore binding to the mutant sites. miR-29 and miR-30 introduction also represses expression of endogenous B-Myb and inhibits cellular DNA synthesis. Finally, interference with miR-29 and miR-30 expression inhibits senescence. These findings demonstrate that miR-29 and miR-30 regulate B-Myb expression by binding to its 3'UTR and suggest that these microRNAs play an important role in Rb-driven cellular senescence.

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