Document Detail


Differential microRNA-34a expression and tumor suppressor function in retinoblastoma cells.
MedLine Citation:
PMID:  19443717     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: The role of miR-34a, a p53-regulated microRNA, in retinoblastoma (RB) was investigated. METHODS: The expression of miR-34 family members in RB cells was determined by semiquantitative RT-PCR and real-time qPCR. Regulation of miR-34a expression by p53-activating compounds was determined by qPCR analysis. The tumor suppressor functions of miR-34a in RB cell lines were determined by tetrazolium-based cell growth assay and by caspase-3/7 and activated caspase-3 apoptotic activity assays. Additive growth inhibitory properties of miR-34a in combination with topotecan were determined by cell growth assay. miR-34a targets in RB cells were identified by real-time qPCR expression analysis of previously reported and GenMiR++-predicted mRNAs. RESULTS: Differential miR-34a and miR-34b expression was observed in RB cell lines and tumor samples. miR-34a expression could be increased in Y79 cells, but not Weri-Rb1 cells, after p53 activation. This differential regulation was not caused by genomic alterations at the miR-34a p53 binding site or mature gene. Exogenous miR-34a inhibited Y79 and Weri-Rb1 cell growth and increased apoptotic activity in Y79 cells. Increased inhibition of Y79 and Weri-Rb1 cell growth was observed with combination miR-34a and topotecan treatment. mRNA expression changes were observed in 7 of 7 previously reported and 13 of 18 GenMiR++-predicted miR-34a targets after transfection of Y79 cells with miR-34a compared with negative control microRNA. CONCLUSIONS: miR-34a functions as a tumor suppressor in RB cells and is a potential therapeutic target. Differential expression, regulation, and activity of miR-34a in RB cells may suggest further p53 pathway inactivation in RB.
Authors:
Clifton L Dalgard; Marco Gonzalez; Jennifer E deNiro; Joan M O'Brien
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2009-05-14
Journal Detail:
Title:  Investigative ophthalmology & visual science     Volume:  50     ISSN:  1552-5783     ISO Abbreviation:  Invest. Ophthalmol. Vis. Sci.     Publication Date:  2009 Oct 
Date Detail:
Created Date:  2009-09-24     Completed Date:  2009-10-02     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7703701     Medline TA:  Invest Ophthalmol Vis Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4542-51     Citation Subset:  IM    
Affiliation:
Ocular Oncology Unit, Department of Ophthalmology, University of California at San Francisco, San Francisco, California 94143, USA.
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MeSH Terms
Descriptor/Qualifier:
Antineoplastic Agents / pharmacology
Apoptosis / drug effects
Blotting, Western
Caspases / metabolism
Cell Survival
Doxorubicin / pharmacology
Gene Expression Regulation, Neoplastic / physiology*
Humans
Imidazoles / pharmacology
MicroRNAs / genetics*
Piperazines / pharmacology
RNA, Messenger / metabolism
Retinal Neoplasms / genetics*,  metabolism,  pathology
Retinoblastoma / genetics*,  metabolism,  pathology
Reverse Transcriptase Polymerase Chain Reaction
Topotecan / pharmacology
Tumor Cells, Cultured
Tumor Suppressor Protein p53 / pharmacology,  physiology*
Grant Support
ID/Acronym/Agency:
EY02162/EY/NEI NIH HHS; R01 EY13812/EY/NEI NIH HHS
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Imidazoles; 0/MIRN34 microRNA, human; 0/MicroRNAs; 0/Piperazines; 0/RNA, Messenger; 0/Tumor Suppressor Protein p53; 0/nutlin 3; 123948-87-8/Topotecan; 23214-92-8/Doxorubicin; EC 3.4.22.-/Caspases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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