Document Detail

The Over-Expression of miR-34a Fails to Block DoHH2 Lymphoma Cell Proliferation by Reducing p53 via c-MYC Down-Regulation.
MedLine Citation:
PMID:  22830357     Owner:  NLM     Status:  Publisher    
MicroRNAs (miRNAs) might behave as tumor suppressors and for that they are under consideration as novel therapeutic drugs. We tested the tumor suppressor activity of miRNA-34a (miR-34a) by measuring cell proliferation of the follicular lymphoma cell line DoHH2 transfected with this miRNA. We report that miR-34a did not inhibit cell proliferation notwithstanding a marked down-regulation of c-MYC. Interestingly, DoHH2 transfected cells showed a significant p53 down-regulation, suggesting that c-MYC positively controls p53 and the failed inhibition of cell proliferation is probably due to the down-regulation of the c-MYC/p53 axis. In keeping with this, c-MYC silencing also down-regulated p53 and had no effect on cell proliferation. In accordance with this hypothesis, etoposide or nutlin-3 treatment or a small interfering RNA (siRNA) against BCL6 (B-cell lymphoma 6) inhibited the proliferation of DoHH2 cells by up-regulating p53 without affecting either miR-34a or c-MYC levels. These results indicate that the proliferation is controlled by the regulatory axis c-MYC/p53 and suggest that paradoxically miR-34a behaves as a pro-proliferative rather than an anti-proliferative miRNA in DoHH2 cells.
Milena Rizzo; Laura Mariani; Sara Cavallini; Marcella Simili; Giuseppe Rainaldi
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-7-25
Journal Detail:
Title:  Nucleic acid therapeutics     Volume:  -     ISSN:  2159-3345     ISO Abbreviation:  -     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-7-26     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101562758     Medline TA:  Nucleic Acid Ther     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
1 Laboratory of Gene and Molecular Therapy, Institute of Clinical Physiology , CNR, Pisa, Italy .
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