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MedLine Citation:
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PMID: 19748357 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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 |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Molecular cell Volume: 35 ISSN: 1097-4164 ISO Abbreviation: Mol. Cell Publication Date: 2009 Sep |
Date Detail:
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Created Date: 2009-09-14 Completed Date: 2009-09-28 Revised Date: 2011-04-27 |
Medline Journal Info:
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Nlm Unique ID: 9802571 Medline TA: Mol Cell Country: United States |
Other Details:
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Languages: eng Pagination: 610-25 Citation Subset: IM |
Affiliation:
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Immune Disease Institute, Children's Hospital Boston, Department of Pediatrics, Harvard Medical School, MA 02115, USA. alal@idi.harvard.edu |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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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 |
| Grant Support | |
ID/Acronym/Agency:
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AI070302/AI/NIAID NIH HHS; U19 AI070302-04/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/3' Untranslated Regions; 0/E2F2 Transcription Factor; 0/E2F2 protein, human; 0/MIRN24 microRNA, human; 0/MYC protein, human; 0/MicroRNAs; 0/Proto-Oncogene Proteins c-myc; 0/RNA, Messenger |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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