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Kaposi's sarcoma herpesvirus (KSHV) microRNA K12-1 functions as an oncogene by activating NF-κB/IL-6/STAT3 signaling
The human oncogenic virus Kaposi's sarcoma herpesvirus (KSHV) is the most common cause of malignancies among AIDS patients. KSHV possesses over hundred genes, including 25 microRNAs (miRNAs). The roles of these miRNAs and many other viral genes in KSHV biology and pathogenesis remain largely un...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5078101/ https://www.ncbi.nlm.nih.gov/pubmed/27166260 http://dx.doi.org/10.18632/oncotarget.9221 |
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author | Chen, Mingqing Sun, Fan Han, Lei Qu, Zhaoxia |
author_facet | Chen, Mingqing Sun, Fan Han, Lei Qu, Zhaoxia |
author_sort | Chen, Mingqing |
collection | PubMed |
description | The human oncogenic virus Kaposi's sarcoma herpesvirus (KSHV) is the most common cause of malignancies among AIDS patients. KSHV possesses over hundred genes, including 25 microRNAs (miRNAs). The roles of these miRNAs and many other viral genes in KSHV biology and pathogenesis remain largely unknown. Accordingly, the molecular mechanisms by which KSHV induces tumorigenesis are still poorly defined. Here, we identify KSHV miRNA K12-1 (miR-K12-1) as a novel viral oncogene by activating two important transcription factors, nuclear factor-κb (NF-κB) and signal transducer and activator of transcription 3 (STAT3). Interestingly, miR-K12-1 activates STAT3 indirectly through inducing NF-κB activation and NF-κB-dependent expression of the cytokine interleukin-6 (IL-6) by repressing the expression of the NF-κB inhibitor IκBα. Accordingly, expression of ectopic IκBα or knockdown of NF-κB RelA, IL-6 or STAT3 prevents expression of cell growth genes and suppresses the oncogenicities of both miR-K12-1 and KSHV. These data identify miR-K12-1/NF-κB/IL-6/STAT3 as a novel oncogenic signaling underlying KSHV tumorigenesis. These data also provide the first evidence showing that IL-6/STAT3 signaling acts as an essential mediator of NF-κB oncogenic actions. These findings significantly improve our understanding of KSHV pathogenesis and oncogenic interaction between NF-κB and STAT3. |
format | Online Article Text |
id | pubmed-5078101 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-50781012016-10-28 Kaposi's sarcoma herpesvirus (KSHV) microRNA K12-1 functions as an oncogene by activating NF-κB/IL-6/STAT3 signaling Chen, Mingqing Sun, Fan Han, Lei Qu, Zhaoxia Oncotarget Research Paper The human oncogenic virus Kaposi's sarcoma herpesvirus (KSHV) is the most common cause of malignancies among AIDS patients. KSHV possesses over hundred genes, including 25 microRNAs (miRNAs). The roles of these miRNAs and many other viral genes in KSHV biology and pathogenesis remain largely unknown. Accordingly, the molecular mechanisms by which KSHV induces tumorigenesis are still poorly defined. Here, we identify KSHV miRNA K12-1 (miR-K12-1) as a novel viral oncogene by activating two important transcription factors, nuclear factor-κb (NF-κB) and signal transducer and activator of transcription 3 (STAT3). Interestingly, miR-K12-1 activates STAT3 indirectly through inducing NF-κB activation and NF-κB-dependent expression of the cytokine interleukin-6 (IL-6) by repressing the expression of the NF-κB inhibitor IκBα. Accordingly, expression of ectopic IκBα or knockdown of NF-κB RelA, IL-6 or STAT3 prevents expression of cell growth genes and suppresses the oncogenicities of both miR-K12-1 and KSHV. These data identify miR-K12-1/NF-κB/IL-6/STAT3 as a novel oncogenic signaling underlying KSHV tumorigenesis. These data also provide the first evidence showing that IL-6/STAT3 signaling acts as an essential mediator of NF-κB oncogenic actions. These findings significantly improve our understanding of KSHV pathogenesis and oncogenic interaction between NF-κB and STAT3. Impact Journals LLC 2016-05-07 /pmc/articles/PMC5078101/ /pubmed/27166260 http://dx.doi.org/10.18632/oncotarget.9221 Text en Copyright: © 2016 Chen et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Chen, Mingqing Sun, Fan Han, Lei Qu, Zhaoxia Kaposi's sarcoma herpesvirus (KSHV) microRNA K12-1 functions as an oncogene by activating NF-κB/IL-6/STAT3 signaling |
title | Kaposi's sarcoma herpesvirus (KSHV) microRNA K12-1 functions as an oncogene by activating NF-κB/IL-6/STAT3 signaling |
title_full | Kaposi's sarcoma herpesvirus (KSHV) microRNA K12-1 functions as an oncogene by activating NF-κB/IL-6/STAT3 signaling |
title_fullStr | Kaposi's sarcoma herpesvirus (KSHV) microRNA K12-1 functions as an oncogene by activating NF-κB/IL-6/STAT3 signaling |
title_full_unstemmed | Kaposi's sarcoma herpesvirus (KSHV) microRNA K12-1 functions as an oncogene by activating NF-κB/IL-6/STAT3 signaling |
title_short | Kaposi's sarcoma herpesvirus (KSHV) microRNA K12-1 functions as an oncogene by activating NF-κB/IL-6/STAT3 signaling |
title_sort | kaposi's sarcoma herpesvirus (kshv) microrna k12-1 functions as an oncogene by activating nf-κb/il-6/stat3 signaling |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5078101/ https://www.ncbi.nlm.nih.gov/pubmed/27166260 http://dx.doi.org/10.18632/oncotarget.9221 |
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