miR-24 Inhibits cell proliferation by targeting E2F2, MYC, and other cell-cycle genes via binding to "seedless" 3'UTR microRNA recognition elements

Mol Cell. 2009 Sep 11;35(5):610-25. doi: 10.1016/j.molcel.2009.08.020.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions*
  • Base Sequence
  • Binding Sites
  • Cell Cycle / genetics*
  • Cell Differentiation / genetics
  • Cell Proliferation*
  • DNA Repair
  • Databases, Genetic
  • Down-Regulation
  • E2F2 Transcription Factor / genetics*
  • Erythrocytes / metabolism
  • Fibroblasts / metabolism
  • Gene Regulatory Networks
  • Genes, cdc*
  • HL-60 Cells
  • Humans
  • K562 Cells
  • Macrophages / metabolism
  • Megakaryocytes / metabolism
  • MicroRNAs / metabolism*
  • Molecular Sequence Data
  • Proto-Oncogene Proteins c-myc / genetics*
  • RNA Interference
  • RNA, Messenger / metabolism
  • Regulatory Sequences, Nucleic Acid*
  • Transcriptional Activation


  • 3' Untranslated Regions
  • E2F2 Transcription Factor
  • E2F2 protein, human
  • MIRN24 microRNA, human
  • MYC protein, human
  • MicroRNAs
  • Proto-Oncogene Proteins c-myc
  • RNA, Messenger