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
; 35(5): 610-25, 2009 Sep 11.
Article
em En
| MEDLINE
| ID: mdl-19748357
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.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Ciclo Celular
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Sequências Reguladoras de Ácido Nucleico
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Proteínas Proto-Oncogênicas c-myc
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Genes cdc
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Regiões 3' não Traduzidas
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MicroRNAs
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Proliferação de Células
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Fator de Transcrição E2F2
Idioma:
En
Ano de publicação:
2009
Tipo de documento:
Article