Target prediction, validation, and functions of viral miRNAs

Tuesday, October 25, 2011 — Poster Session II
Noon – 2:00 p.m.	Natcher Conference Center	NCI	SIG/RNA/CYTOK-1

Authors

• J Abend
• P Kieffer-Kwon
• J Ji
• V Flowers
• A Gallaher
• J Ziegelbauer

Abstract

Kaposi's sarcoma-associated herpesvirus (KSHV) encodes multiple microRNAs and is the responsible agent for Kaposi's sarcoma (KS), primary effusion lymphoma and multicentric Castleman's disease. We integrated our expression data from multiple gain and loss of KSHV microRNA function experiments to make unbiased systematic microRNA target predictions based solely on expression analysis. We have tested forty-nine predicted target genes and twenty-eight target genes were significantly inhibited using luciferase assays. More than half of the microRNA target interactions are not detected using bioinformatic methods which search for seed-matching sequences. In order to complement our mRNA expression profiling dataset, we have completed a proteomic screen to assess changes in protein expression as a result of KSHV microRNA expression. Our analysis identified a published KSHV microRNA human target gene in addition to other novel target genes. Many targets are involved with regulation of the cell cycle, apoptosis and other cancer-related functions. We discovered a specific KSHV microRNA inhibits cytokine-induced apoptosis and also suppresses a pro-inflammatory cytokine response. This represents a mechanism for KSHV to avoid death of an infected cell during latency and to inhibit immune responses by the host. These results have implications regarding microRNA target prediction and KSHV pathogenesis.

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