| microRNA-21 negatively regulates Cdc25A and cell cycle progression in colon cancer cells. | |
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MedLine Citation:
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PMID: 19826040 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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microRNAs (miRNA) are small noncoding RNAs that participate in diverse biological processes by suppressing target gene expression. Altered expression of miR-21 has been reported in cancer. To gain insights into its potential role in tumorigenesis, we generated miR-21 knockout colon cancer cells through gene targeting. Unbiased microarray analysis combined with bioinformatics identified cell cycle regulator Cdc25A as a miR-21 target. miR-21 suppressed Cdc25A expression through a defined sequence in its 3'-untranslated region. We found that miR-21 is induced by serum starvation and DNA damage, negatively regulates G(1)-S transition, and participates in DNA damage-induced G(2)-M checkpoint through down-regulation of Cdc25A. In contrast, miR-21 deficiency did not affect apoptosis induced by a variety of commonly used anticancer agents or cell proliferation under normal cell culture conditions. Furthermore, miR-21 was found to be underexpressed in a subset of Cdc25A-overexpressing colon cancers. Our data show a role of miR-21 in modulating cell cycle progression following stress, providing a novel mechanism of Cdc25A regulation and a potential explanation of miR-21 in tumorigenesis. |
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Authors:
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Peng Wang; Fangdong Zou; Xiaodong Zhang; Hua Li; Austin Dulak; Robert J Tomko; John S Lazo; Zhenghe Wang; Lin Zhang; Jian Yu |
Publication Detail:
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Type: Journal Article Date: 2009-10-13 |
Journal Detail:
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Title: Cancer research Volume: 69 ISSN: 1538-7445 ISO Abbreviation: Cancer Res. Publication Date: 2009 Oct |
Date Detail:
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Created Date: 2009-10-16 Completed Date: 2009-11-24 Revised Date: 2012-04-05 |
Medline Journal Info:
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Nlm Unique ID: 2984705R Medline TA: Cancer Res Country: United States |
Other Details:
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Languages: eng Pagination: 8157-65 Citation Subset: IM |
Affiliation:
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Departments of Pathology and Pharmacology, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Apoptosis Bromodeoxyuridine / diagnostic use Cell Cycle* Cell Proliferation Colorectal Neoplasms / genetics*, metabolism, pathology* DNA Damage Gene Expression Profiling Gene Expression Regulation, Neoplastic* Humans Luciferases / metabolism MicroRNAs / physiology* Mitotic Index Oligonucleotide Array Sequence Analysis RNA, Messenger / genetics, metabolism RNA, Small Interfering / pharmacology Reverse Transcriptase Polymerase Chain Reaction cdc25 Phosphatases |
| Grant Support | |
ID/Acronym/Agency:
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R01 CA106348-01/CA/NCI NIH HHS; R01 CA106348-02/CA/NCI NIH HHS; R01 CA106348-03/CA/NCI NIH HHS; R01 CA106348-04/CA/NCI NIH HHS; R01 CA106348-05/CA/NCI NIH HHS; R01 CA121105-01A1/CA/NCI NIH HHS; R01 CA121105-02/CA/NCI NIH HHS; R01 CA121105-03/CA/NCI NIH HHS; R01 CA129829-01A1/CA/NCI NIH HHS; R01 CA129829-02/CA/NCI NIH HHS; R01 CA129829-05/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/MIRN21 microRNA, human; 0/MicroRNAs; 0/RNA, Messenger; 0/RNA, Small Interfering; 59-14-3/Bromodeoxyuridine; EC 1.13.12.-/Luciferases; EC 3.1.3.48/CDC25A protein, human; EC 3.1.3.48/cdc25 Phosphatases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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