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

Area of Science:

• Molecular Biology
• Oncology
• Virology

Background:

• MicroRNAs (miRNAs) are small non-coding RNAs regulating gene expression.
• Circulating miRNAs and exosomal miRNAs are emerging as potential disease biomarkers, particularly for cancers.
• Kaposi's sarcoma (KS), an AIDS-associated cancer caused by KSHV, and Primary Effusion Lymphoma (PEL) are studied.

Purpose of the Study:

• To identify host and viral circulating miRNAs in patients with KSHV-associated malignancies (KS and PEL).
• To analyze circulating and exosomal miRNAs in KSHV-infected mouse models.
• To investigate the functional role of exosomes derived from KSHV-associated malignancies.

Main Methods:

• Detection and characterization of circulating and exosomal miRNAs from patient biofluids (plasma, pleural fluid, serum) and KSHV mouse models.
• Exosome isolation and miRNA profiling.
• Gene ontology analysis of exosomal miRNA targets and functional assays on endothelial cells exposed to patient-derived exosomes.

Main Results:

• Both KSHV-encoded and host miRNAs (including miR-17-92 cluster) were detected in patient exosomes and circulating profiles from KSHV mouse models.
• A specific subset of miRNAs was preferentially incorporated into exosomes.
• Patient-derived exosomes promoted endothelial cell migration and IL-6 secretion, indicating functional activity.

Conclusions:

• Exosomes from KSHV-associated malignancies contain a distinct miRNA signature.
• These exosomal miRNAs may serve as candidate biomarkers for KS and PEL.
• Functional exosomes contribute to the paracrine phenotype characteristic of KS.