Circulating microRNAs (miRNAs), such as those found in exosomes, have emerged as diagnostic tools and hold promise as minimally invasive, stable biomarkers. Transfer of tumor-derived exosomal miRNAs to surrounding cells may be an important form of cellular communication. Kaposi’s sarcoma-associated herpesvirus (KSHV) is the etiological agent of Kaposi’s sarcoma (KS), the most common AIDS-defining cancer worldwide. Here, a team led by researchers at the University of North Carolina at Chapel Hill survey systemically circulating miRNAs and reveal potential biomarkers for KS and Primary Effusion Lymphoma (PEL). This expands previous tissue culture studies by profiling clinical samples and by using two new mouse models of KSHV tumorigenesis. Profiling of circulating miRNAs revealed that oncogenic and viral miRNAs were present in exosomes from KS patient plasma, pleural effusions and mouse models of KS. Analysis of human oncogenic miRNAs, including the well-known miR-17-92 cluster, revealed that several miRNAs were preferentially incorporated into exosomes in our KS mouse model. Gene ontology analysis of upregulated miRNAs showed that the majority of pathways affected were known targets of KSHV signaling pathways. Transfer of these oncogenic exosomes to immortalized hTERT-HUVEC cells enhanced cell migration and IL-6 secretion. These circulating miRNAs and KS derived exosomes may therefore be part of the paracrine signaling mechanism that mediates KSHV pathogenesis.
- Chugh PE, Sin S-H, Ozgur S, Henry DH, Menezes P, et al. (2013) Systemically Circulating Viral and Tumor-Derived MicroRNAs in KSHV-Associated Malignancies. PLoS Pathog 9(7), e1003484. [article]