Systemically circulating viral and tumor-derived microRNAs in KSHV-associated malignancies.

MicroRNAs (miRNAs) are stable, small non-coding RNAs that modulate many downstream target genes. Recently, circulating miRNAs have been detected in various body fluids and within exosomes, prompting their evaluation as candidate biomarkers of diseases, especially cancer. Kaposi's sarcoma (KS) i...

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Autores principales: Pauline E Chugh, Sang-Hoon Sin, Sezgin Ozgur, David H Henry, Prema Menezes, Jack Griffith, Joseph J Eron, Blossom Damania, Dirk P Dittmer
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Publicado: Public Library of Science (PLoS) 2013
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Acceso en línea:https://doaj.org/article/b16e1b81183045c0b0f5e83a301ce1a8
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spelling oai:doaj.org-article:b16e1b81183045c0b0f5e83a301ce1a82021-11-18T06:05:22ZSystemically circulating viral and tumor-derived microRNAs in KSHV-associated malignancies.1553-73661553-737410.1371/journal.ppat.1003484https://doaj.org/article/b16e1b81183045c0b0f5e83a301ce1a82013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23874201/pdf/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374MicroRNAs (miRNAs) are stable, small non-coding RNAs that modulate many downstream target genes. Recently, circulating miRNAs have been detected in various body fluids and within exosomes, prompting their evaluation as candidate biomarkers of diseases, especially cancer. Kaposi's sarcoma (KS) is the most common AIDS-associated cancer and remains prevalent despite Highly Active Anti-Retroviral Therapy (HAART). KS is caused by KS-associated herpesvirus (KSHV), a gamma herpesvirus also associated with Primary Effusion Lymphoma (PEL). We sought to determine the host and viral circulating miRNAs in plasma, pleural fluid or serum from patients with the KSHV-associated malignancies KS and PEL and from two mouse models of KS. Both KSHV-encoded miRNAs and host miRNAs, including members of the miR-17-92 cluster, were detectable within patient exosomes and circulating miRNA profiles from KSHV mouse models. Further characterization revealed a subset of miRNAs that seemed to be preferentially incorporated into exosomes. Gene ontology analysis of signature exosomal miRNA targets revealed several signaling pathways that are known to be important in KSHV pathogenesis. Functional analysis of endothelial cells exposed to patient-derived exosomes demonstrated enhanced cell migration and IL-6 secretion. This suggests that exosomes derived from KSHV-associated malignancies are functional and contain a distinct subset of miRNAs. These could represent candidate biomarkers of disease and may contribute to the paracrine phenotypes that are a characteristic of KS.Pauline E ChughSang-Hoon SinSezgin OzgurDavid H HenryPrema MenezesJack GriffithJoseph J EronBlossom DamaniaDirk P DittmerPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 9, Iss 7, p e1003484 (2013)
institution DOAJ
collection DOAJ
language EN
topic Immunologic diseases. Allergy
RC581-607
Biology (General)
QH301-705.5
spellingShingle Immunologic diseases. Allergy
RC581-607
Biology (General)
QH301-705.5
Pauline E Chugh
Sang-Hoon Sin
Sezgin Ozgur
David H Henry
Prema Menezes
Jack Griffith
Joseph J Eron
Blossom Damania
Dirk P Dittmer
Systemically circulating viral and tumor-derived microRNAs in KSHV-associated malignancies.
description MicroRNAs (miRNAs) are stable, small non-coding RNAs that modulate many downstream target genes. Recently, circulating miRNAs have been detected in various body fluids and within exosomes, prompting their evaluation as candidate biomarkers of diseases, especially cancer. Kaposi's sarcoma (KS) is the most common AIDS-associated cancer and remains prevalent despite Highly Active Anti-Retroviral Therapy (HAART). KS is caused by KS-associated herpesvirus (KSHV), a gamma herpesvirus also associated with Primary Effusion Lymphoma (PEL). We sought to determine the host and viral circulating miRNAs in plasma, pleural fluid or serum from patients with the KSHV-associated malignancies KS and PEL and from two mouse models of KS. Both KSHV-encoded miRNAs and host miRNAs, including members of the miR-17-92 cluster, were detectable within patient exosomes and circulating miRNA profiles from KSHV mouse models. Further characterization revealed a subset of miRNAs that seemed to be preferentially incorporated into exosomes. Gene ontology analysis of signature exosomal miRNA targets revealed several signaling pathways that are known to be important in KSHV pathogenesis. Functional analysis of endothelial cells exposed to patient-derived exosomes demonstrated enhanced cell migration and IL-6 secretion. This suggests that exosomes derived from KSHV-associated malignancies are functional and contain a distinct subset of miRNAs. These could represent candidate biomarkers of disease and may contribute to the paracrine phenotypes that are a characteristic of KS.
format article
author Pauline E Chugh
Sang-Hoon Sin
Sezgin Ozgur
David H Henry
Prema Menezes
Jack Griffith
Joseph J Eron
Blossom Damania
Dirk P Dittmer
author_facet Pauline E Chugh
Sang-Hoon Sin
Sezgin Ozgur
David H Henry
Prema Menezes
Jack Griffith
Joseph J Eron
Blossom Damania
Dirk P Dittmer
author_sort Pauline E Chugh
title Systemically circulating viral and tumor-derived microRNAs in KSHV-associated malignancies.
title_short Systemically circulating viral and tumor-derived microRNAs in KSHV-associated malignancies.
title_full Systemically circulating viral and tumor-derived microRNAs in KSHV-associated malignancies.
title_fullStr Systemically circulating viral and tumor-derived microRNAs in KSHV-associated malignancies.
title_full_unstemmed Systemically circulating viral and tumor-derived microRNAs in KSHV-associated malignancies.
title_sort systemically circulating viral and tumor-derived micrornas in kshv-associated malignancies.
publisher Public Library of Science (PLoS)
publishDate 2013
url https://doaj.org/article/b16e1b81183045c0b0f5e83a301ce1a8
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