Journal article
miR-24 Inhibits Cell Proliferation by Targeting E2F2, MYC, and Other Cell-Cycle Genes via Binding to "Seedless" 3′UTR MicroRNA Recognition Elements
A Lal, F Navarro, CA Maher, LE Maliszewski, N Yan, E O'Day, D Chowdhury, DM Dykxhoorn, P Tsai, O Hofmann, KG Becker, M Gorospe, W Hide, J Lieberman
Molecular Cell | CELL PRESS | Published : 2009
Abstract
miR-24, upregulated during terminal differentiation of multiple lineages, inhibits cell-cycle progression. Antagonizing miR-24 restores postmitotic cell proliferation and enhances fibroblast proliferation, whereas overexpressing miR-24 increases the G1 compartment. The 248 mRNAs downregulated upon miR-24 overexpression are highly enriched for DNA repair and cell-cycle regulatory genes that form a direct interaction network with prominent nodes at genes that enhance (MYC, E2F2, CCNB1, and CDC2) or inhibit (p27Kip1 and VHL) cell-cycle progression. miR-24 directly regulates MYC and E2F2 and some genes that they transactivate. Enhanced proliferation from antagonizing miR-24 is abrogated by knock..
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Awarded by National Institutes of Health
Funding Acknowledgements
This work was supported, in part, by National Institutes of Health (NIH) A1070302 and a GSK-IDI Alliance grant (J.L.); the NIA-IRP, NIH (K.G.B., M.G.); the Harry Oppenheimer Memorial Trust (W.H.); a GSK-IDI Alliance fellowship (F.N.); and the Harvard Center for AIDS Research (N.Y.). We thank N. Dyson (Harvard Medical School) for the HA-E2F2 expression plasmid, Ray McGovern for programming support, and Lieberman laboratory members for useful discussions.