| miR-335 directly targets Rb1 (pRb/p105) in a proximal connection to p53-dependent stress response. | |
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MedLine Citation:
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PMID: 20713524 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Loss-of-function mutations of retinoblastoma family (Rb) proteins drive tumorigenesis by overcoming barriers to cellular proliferation. Consequently, factors modulating Rb function are of great clinical import. Here, we show that miR-335 is differentially expressed in human cancer cells and that it tightly regulates the expression of Rb1 (pRb/p105) by specifically targeting a conserved sequence motif in its 3' untranslated region. We found that by altering Rb1 (pRb/p105) levels, miR-335 activates the p53 tumor suppressor pathway to limit cell proliferation and neoplastic cell transformation. DNA damage elicited an increase in miR-335 expression in a p53-dependent manner. miR-335 and p53 cooperated in a positive feedback loop to drive cell cycle arrest. Together, these results indicate that miR-335 helps control proliferation by balancing the activities of the Rb and p53 tumor suppressor pathways. Further, they establish that miR-335 activation plays an important role in the induction of p53-dependent cell cycle arrest after DNA damage. |
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Authors:
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Michele Scarola; Stefan Schoeftner; Claudio Schneider; Roberta Benetti |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-08-16 |
Journal Detail:
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Title: Cancer research Volume: 70 ISSN: 1538-7445 ISO Abbreviation: Cancer Res. Publication Date: 2010 Sep |
Date Detail:
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Created Date: 2010-09-02 Completed Date: 2010-10-07 Revised Date: - |
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: 6925-33 Citation Subset: IM |
Affiliation:
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Laboratorio Nazionale Consorzio Interuniversitario Biotecnologie, Cancer Epigenetics Program, Trieste, Italy. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Cycle Cell Growth Processes / genetics Cell Line, Tumor DNA Damage Feedback Humans Mice MicroRNAs / biosynthesis, genetics* NIH 3T3 Cells Neoplasms / genetics*, metabolism, pathology RNA, Small Interfering / genetics Retinoblastoma Protein / biosynthesis, genetics*, metabolism Transfection Tumor Suppressor Protein p53 / metabolism* |
| Chemical | |
Reg. No./Substance:
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0/MicroRNAs; 0/Mirn335 microRNA, mouse; 0/RNA, Small Interfering; 0/Retinoblastoma Protein; 0/Tumor Suppressor Protein p53 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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