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Kaposi's sarcoma herpesvirus microRNAs target caspase 3 and regulate apoptosis
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نویسنده
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suffert g. ,malterer g. ,hausser j. ,viiliäinen j. ,fender a. ,contrant m. ,ivacevic t. ,benes v. ,gros f. ,voinnet o. ,zavolan m. ,ojala p.m. ,haas j.g. ,pfeffer s.
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منبع
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plos pathogens - 2011 - دوره : 7 - شماره : 12
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چکیده
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Kaposi's sarcoma herpesvirus (kshv) encodes a cluster of twelve micro (mi)rnas,which are abundantly expressed during both latent and lytic infection. previous studies reported that kshv is able to inhibit apoptosis during latent infection; we thus tested the involvement of viral mirnas in this process. we found that both hek293 epithelial cells and dg75 cells stably expressing kshv mirnas were protected from apoptosis. potential cellular targets that were significantly down-regulated upon kshv mirnas expression were identified by microarray profiling. among them,we validated by luciferase reporter assays,quantitative pcr and western blotting caspase 3 (casp3),a critical factor for the control of apoptosis. using site-directed mutagenesis,we found that three kshv mirnas,mir-k12-1,3 and 4-3p,were responsible for the targeting of casp3. specific inhibition of these mirnas in kshv-infected cells resulted in increased expression levels of endogenous casp3 and enhanced apoptosis. altogether,our results suggest that kshv mirnas directly participate in the previously reported inhibition of apoptosis by the virus,and are thus likely to play a role in kshv-induced oncogenesis. © 2011 suffert et al.
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آدرس
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architecture et réactivité de l'arn,institut de biologie moléculaire et cellulaire du cnrs,université de strasbourg,strasbourg, France, max von pettenkofer-institute,ludwig-maximilians-university munich,munich, Germany, biozentrum der universität basel and swiss institute of bioinformatics,basel, Switzerland, genome-scale biology program,biomedicum helsinki and institute of biomedicine,university of helsinki,helsinki,finland,institute of biotechnology,university of helsinki,helsinki, Finland, architecture et réactivité de l'arn,institut de biologie moléculaire et cellulaire du cnrs,université de strasbourg,strasbourg, France, architecture et réactivité de l'arn,institut de biologie moléculaire et cellulaire du cnrs,université de strasbourg,strasbourg, France, genecore (genomics core facility),embl,heidelberg, Germany, genecore (genomics core facility),embl,heidelberg, Germany, immunologie et chimie thérapeutiques upr 9021,institut de biologie moléculaire et cellulaire du cnrs,université de strasbourg,strasbourg, France, institut de biologie moléculaire des plantes du cnrs,strasbourg, France, biozentrum der universität basel and swiss institute of bioinformatics,basel, Switzerland, genome-scale biology program,biomedicum helsinki and institute of biomedicine,university of helsinki,helsinki,finland,foundation for the finnish cancer institute,helsinki,finland,institute of biotechnology,university of helsinki,helsinki, Finland, max von pettenkofer-institute,ludwig-maximilians-university munich,munich,germany,division of pathway medicine,university of edinburgh medical school,edinburgh, United Kingdom, architecture et réactivité de l'arn,institut de biologie moléculaire et cellulaire du cnrs,université de strasbourg,strasbourg, France
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Authors
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