Document Detail


miR-335 directly targets Rb1 (pRb/p105) in a proximal connection to p53-dependent stress response.
MedLine Citation:
PMID:  20713524     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Michele Scarola; Stefan Schoeftner; Claudio Schneider; Roberta Benetti
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-08-16
Journal Detail:
Title:  Cancer research     Volume:  70     ISSN:  1538-7445     ISO Abbreviation:  Cancer Res.     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-09-02     Completed Date:  2010-10-07     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2984705R     Medline TA:  Cancer Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  6925-33     Citation Subset:  IM    
Affiliation:
Laboratorio Nazionale Consorzio Interuniversitario Biotecnologie, Cancer Epigenetics Program, Trieste, Italy.
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MeSH Terms
Descriptor/Qualifier:
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:
0/MicroRNAs; 0/Mirn335 microRNA, mouse; 0/RNA, Small Interfering; 0/Retinoblastoma Protein; 0/Tumor Suppressor Protein p53

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