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Kaposi's sarcoma associated herpesvirus-encoded viral FLICE inhibitory protein (vFLIP) K13 suppresses CXCR4 expression by upregulating miR-146a

Kaposi's sarcoma (KS) associated herpesvirus (KSHV)-encoded viral FLICE inhibitory protein (vFLIP) K13 is a potent activator of the NF-κB pathway. Here we demonstrate that infection with KHSV and ectopic expression of K13, but not its NF-κB-defective mutant, suppressed the expression of CXCR4....

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Autores principales: Punj, Vasu, Matta, Hittu, Schamus, Sandra, Tamewitz, Aletheia, Anyang, Bean, Chaudhary, Preet M.
Formato: Texto
Lenguaje:English
Publicado: 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2845732/
https://www.ncbi.nlm.nih.gov/pubmed/20023696
http://dx.doi.org/10.1038/onc.2009.460
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author Punj, Vasu
Matta, Hittu
Schamus, Sandra
Tamewitz, Aletheia
Anyang, Bean
Chaudhary, Preet M.
author_facet Punj, Vasu
Matta, Hittu
Schamus, Sandra
Tamewitz, Aletheia
Anyang, Bean
Chaudhary, Preet M.
author_sort Punj, Vasu
collection PubMed
description Kaposi's sarcoma (KS) associated herpesvirus (KSHV)-encoded viral FLICE inhibitory protein (vFLIP) K13 is a potent activator of the NF-κB pathway. Here we demonstrate that infection with KHSV and ectopic expression of K13, but not its NF-κB-defective mutant, suppressed the expression of CXCR4. Suppression of CXCR4 by KSHV and K13 was associated with upregulated expression of miR-146a, a microRNA that is known to bind to the 3′ untranslated region of CXCR4 mRNA. Reporter studies identified two NF-κB sites in the promoter of miR-146a that were essential for its activation by K13. Accordingly, ectopic expression of K13, but not its NF-κB-defective mutant or other vFLIPs, strongly stimulated the miR-146a promoter activity, which could be blocked by specific genetic and pharmacological inhibitors of the NF-κB pathway. Finally, expression of CXCR4 was downregulated in clinical samples of KS and this was accompanied by increased expression of miR-146a. Our results demonstrate that K13-induced NF-κB activity suppresses CXCR4 via upregulation of miR-146a. Downregulation of CXCR4 expression by K13 may contribute to KS development by promoting premature release of KSHV-infected endothelial progenitors into the circulation.
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spelling pubmed-28457322010-09-25 Kaposi's sarcoma associated herpesvirus-encoded viral FLICE inhibitory protein (vFLIP) K13 suppresses CXCR4 expression by upregulating miR-146a Punj, Vasu Matta, Hittu Schamus, Sandra Tamewitz, Aletheia Anyang, Bean Chaudhary, Preet M. Oncogene Article Kaposi's sarcoma (KS) associated herpesvirus (KSHV)-encoded viral FLICE inhibitory protein (vFLIP) K13 is a potent activator of the NF-κB pathway. Here we demonstrate that infection with KHSV and ectopic expression of K13, but not its NF-κB-defective mutant, suppressed the expression of CXCR4. Suppression of CXCR4 by KSHV and K13 was associated with upregulated expression of miR-146a, a microRNA that is known to bind to the 3′ untranslated region of CXCR4 mRNA. Reporter studies identified two NF-κB sites in the promoter of miR-146a that were essential for its activation by K13. Accordingly, ectopic expression of K13, but not its NF-κB-defective mutant or other vFLIPs, strongly stimulated the miR-146a promoter activity, which could be blocked by specific genetic and pharmacological inhibitors of the NF-κB pathway. Finally, expression of CXCR4 was downregulated in clinical samples of KS and this was accompanied by increased expression of miR-146a. Our results demonstrate that K13-induced NF-κB activity suppresses CXCR4 via upregulation of miR-146a. Downregulation of CXCR4 expression by K13 may contribute to KS development by promoting premature release of KSHV-infected endothelial progenitors into the circulation. 2009-12-21 2010-03-25 /pmc/articles/PMC2845732/ /pubmed/20023696 http://dx.doi.org/10.1038/onc.2009.460 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Punj, Vasu
Matta, Hittu
Schamus, Sandra
Tamewitz, Aletheia
Anyang, Bean
Chaudhary, Preet M.
Kaposi's sarcoma associated herpesvirus-encoded viral FLICE inhibitory protein (vFLIP) K13 suppresses CXCR4 expression by upregulating miR-146a
title Kaposi's sarcoma associated herpesvirus-encoded viral FLICE inhibitory protein (vFLIP) K13 suppresses CXCR4 expression by upregulating miR-146a
title_full Kaposi's sarcoma associated herpesvirus-encoded viral FLICE inhibitory protein (vFLIP) K13 suppresses CXCR4 expression by upregulating miR-146a
title_fullStr Kaposi's sarcoma associated herpesvirus-encoded viral FLICE inhibitory protein (vFLIP) K13 suppresses CXCR4 expression by upregulating miR-146a
title_full_unstemmed Kaposi's sarcoma associated herpesvirus-encoded viral FLICE inhibitory protein (vFLIP) K13 suppresses CXCR4 expression by upregulating miR-146a
title_short Kaposi's sarcoma associated herpesvirus-encoded viral FLICE inhibitory protein (vFLIP) K13 suppresses CXCR4 expression by upregulating miR-146a
title_sort kaposi's sarcoma associated herpesvirus-encoded viral flice inhibitory protein (vflip) k13 suppresses cxcr4 expression by upregulating mir-146a
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2845732/
https://www.ncbi.nlm.nih.gov/pubmed/20023696
http://dx.doi.org/10.1038/onc.2009.460
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