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

doi:10.1016/j.molcel.2009.08.020

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

Journal article

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Peer reviewed

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, …

Molecular cell, Vol.35(5), pp.610-625

2009

DOI: https://doi.org/10.1016/j.molcel.2009.08.020

PMID: 19748357

Abstract

RNA

CELLCYCLE

DNA

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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Collaboration types: Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.196 Micro & Long Noncoding RNA; 1.196.68 MicroRNAs
Web Of Science research areas: Biochemistry & Molecular Biology; Cell Biology
ESI research areas: Molecular Biology & Genetics

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Title: miR-24 Inhibits Cell Proliferation by Targeting E2F2, MYC, and Other Cell-Cycle Genes via Binding to “Seedless” 3′UTR MicroRNA Recognition Elements
Creators: Ashish Lal - Immune Disease Institute, Program in Cellular and Molecular Medicine, Children's Hospital Boston and Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA
Francisco Navarro - Immune Disease Institute, Program in Cellular and Molecular Medicine, Children's Hospital Boston and Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA
Christopher A Maher - Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, USA
Laura E Maliszewski - Immune Disease Institute, Program in Cellular and Molecular Medicine, Children's Hospital Boston and Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA
Nan Yan - Immune Disease Institute, Program in Cellular and Molecular Medicine, Children's Hospital Boston and Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA
Elizabeth O'Day - Immune Disease Institute, Program in Cellular and Molecular Medicine, Children's Hospital Boston and Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA
Dipanjan Chowdhury - Immune Disease Institute, Program in Cellular and Molecular Medicine, Children's Hospital Boston and Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA
Derek M Dykxhoorn - Immune Disease Institute, Program in Cellular and Molecular Medicine, Children's Hospital Boston and Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA
Perry Tsai - Immune Disease Institute, Program in Cellular and Molecular Medicine, Children's Hospital Boston and Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA
Oliver Hofmann - Department of Biostatistics, Harvard School of Public Health, Boston, MA 02115, USA
Kevin G Becker - Research Resources Branch and Laboratory of Cellular and Molecular Biology, National Institute on Aging-IRP, National Institutes of Health, Baltimore, MD 21224, USA
Myriam Gorospe - Research Resources Branch and Laboratory of Cellular and Molecular Biology, National Institute on Aging-IRP, National Institutes of Health, Baltimore, MD 21224, USA
Winston Hide - Department of Biostatistics, Harvard School of Public Health, Boston, MA 02115, USA
Judy Lieberman - Immune Disease Institute, Program in Cellular and Molecular Medicine, Children's Hospital Boston and Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA
Publication Details: Molecular cell, Vol.35(5), pp.610-625
Publisher: Elsevier Inc
Academic Unit: Miller School of Medicine; John P. Hussman Institute for Human Genomics; UMMG Dept of Human Genetics (Dr. John T. Macdonald Foundation)
Language: English
Resource Type: Journal article
PMID: 19748357
Record Identifier: 991031560118602976