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The RNA Activator ds-p21 Potentiates the Cytotoxicity Induced by Fludarabine in Dohh2 Cells.
MedLine Citation:
PMID:  21241187     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Recently, it has been reported that, in several tumor cell lines, short double-stranded RNAs tailored for promoter regions of specific genes are able to activate their transcription. Such molecules (named RNA activators) act opposite to other double-stranded RNA molecules (named RNA inhibitors) in that the overexpression instead of underexpression of a given gene is triggered. In Dohh2 non-Hodgkin lymphoma cells, the transcriptional repressor BCL6, which negatively controls both p53 and p21, is overexpressed, so that the cells can escape the check point governed by p53 and proliferate. The aim of this work was to investigate whether the RNA activator p21 can represent a tool to circumvent the transcriptional control of BCL6 and induce the blockage of cell proliferation in Dohh2 non-Hodgkin lymphoma cells. For that, Dohh2 cells were transfected with either a control RNA activator (ds-NC) or an RNA activator specific for human p21 promoter (ds-p21). At various time points after transfection, the cells were collected and p21 was measured. Dohh2 cells transfected with ds-p21 showed a slight but significant overexpression of p21 at both mRNA and protein levels. Nonetheless, cell proliferation, cell cycle, and apoptosis were not significantly modified. In contrast, the exposure of Dohh2 cells transfected with ds-p21 to fludarabine potentiates the cytotoxicity of the drug, suggesting the RNA activator p21 complements the fludarabine-dependent cell death pathways.
Authors:
Francesca Patella; Serena Lucotti; Milena Rizzo; Monica Evangelista; Giuseppe Rainaldi
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-1-17
Journal Detail:
Title:  Oligonucleotides     Volume:  -     ISSN:  1557-8526     ISO Abbreviation:  -     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2011-1-18     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101188415     Medline TA:  Oligonucleotides     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
1 Laboratory of Gene and Molecular Therapy, Institute of Clinical Physiology , CNR, Pisa, Italy .
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