Document Detail


Marek's disease virus type 1 microRNA miR-M3 suppresses cisplatin-induced apoptosis by targeting Smad2 of the transforming growth factor beta signal pathway.
MedLine Citation:
PMID:  20962090     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Viruses cause about 15% of the cancers that are still the leading causes of human mortality. The discovery of viral oncogenes has enhanced our understanding of viral oncogenesis. However, the underlying molecular mechanisms of virus-induced cancers are complex and require further investigation. The present study has attempted to investigate the effects of the microRNAs (miRNAs) encoded by Marek's disease virus 1 (MDV1), a chicken herpesvirus causing acute T-cell lymphomas and solid visceral tumors in chickens, on anti-cancer drug-induced apoptosis and identify the targets of the miRNAs. The results showed that of the total 14 miRNAs encoded by MDV1, MDV1-miR-M3 significantly promoted cell survival under treatment with cisplatin, a widely used chemotherapy drug. MDV1-miR-M3 suppressed cisplatin-induced apoptosis by directly downregulating expression at the protein but not the mRNA level of Smad2, a critical component in the transforming growth factor β signal pathway. Our data suggest that latent/oncogenic viruses may encode miRNAs to directly target cellular factors involved in antiviral processes including apoptosis, thus proactively creating a cellular environment beneficial to viral latency and oncogenesis. Furthermore, the knowledge of the apoptosis resistance conferred by viral miRNAs has great practical implications for improving the efficacy of chemotherapies for treating cancers, especially those induced by oncogenic viruses.
Authors:
Shun Xu; Chunyi Xue; Jianping Li; Yingzuo Bi; Yongchang Cao
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-10-20
Journal Detail:
Title:  Journal of virology     Volume:  85     ISSN:  1098-5514     ISO Abbreviation:  J. Virol.     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2010-12-14     Completed Date:  2011-01-20     Revised Date:  2011-08-01    
Medline Journal Info:
Nlm Unique ID:  0113724     Medline TA:  J Virol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  276-85     Citation Subset:  IM    
Affiliation:
State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou 510006, People's Republic of China.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antineoplastic Agents / pharmacology*
Apoptosis / drug effects*
Cell Survival
Chick Embryo
Cisplatin / pharmacology*
Down-Regulation*
Fibroblasts / virology
Gene Expression Regulation
Herpesvirus 2, Gallid / genetics,  metabolism,  pathogenicity
Humans
Marek Disease / pathology,  virology
MicroRNAs / genetics,  metabolism,  pharmacology*
Signal Transduction
Smad2 Protein / genetics,  metabolism*
Transforming Growth Factor beta / genetics,  metabolism
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/MicroRNAs; 0/Smad2 Protein; 0/Transforming Growth Factor beta; 15663-27-1/Cisplatin
Comments/Corrections

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