miR-24 Inhibits Cell Proliferation by Targeting E2F2, MYC, and Other Cell-Cycle Genes via Binding to "Seedless" 3′UTR MicroRNA Recognition Elements

Ashish Lal, Francisco Navarro, Christopher A. Maher, Laura E. Maliszewski, Nan Yan, Elizabeth O'Day, Dipanjan Chowdhury, Derek M. Dykxhoorn, Perry Tsai, Oliver Hofmann, Kevin G. Becker, Myriam Gorospe, Winston Hide, Judy Lieberman

Research output: Contribution to journalArticle

440 Scopus citations

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 knocking down E2F2, but not MYC, and cell proliferation, inhibited by miR-24 overexpression, is rescued by miR-24-insensitive E2F2. Therefore, E2F2 is a critical miR-24 target. The E2F2 3′UTR lacks a predicted miR-24 recognition element. In fact, miR-24 regulates expression of E2F2, MYC, AURKB, CCNA2, CDC2, CDK4, and FEN1 by recognizing seedless but highly complementary sequences.

Original languageEnglish (US)
Pages (from-to)610-625
Number of pages16
JournalMolecular Cell
Volume35
Issue number5
DOIs
StatePublished - Sep 11 2009

Keywords

  • CELLCYCLE
  • DNA
  • RNA

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'miR-24 Inhibits Cell Proliferation by Targeting E2F2, MYC, and Other Cell-Cycle Genes via Binding to "Seedless" 3′UTR MicroRNA Recognition Elements'. Together they form a unique fingerprint.

  • Cite this

    Lal, A., Navarro, F., Maher, C. A., Maliszewski, L. E., Yan, N., O'Day, E., Chowdhury, D., Dykxhoorn, D. M., Tsai, P., Hofmann, O., Becker, K. G., Gorospe, M., Hide, W., & Lieberman, J. (2009). miR-24 Inhibits Cell Proliferation by Targeting E2F2, MYC, and Other Cell-Cycle Genes via Binding to "Seedless" 3′UTR MicroRNA Recognition Elements. Molecular Cell, 35(5), 610-625. https://doi.org/10.1016/j.molcel.2009.08.020