Functional dissection of human targets for KSHV-encoded miRNAs using network analysis.

Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiological agent of Kaposi's sarcoma, primary effusion lymphoma and multicentric Castleman's disease, etc. In this study, we firstly systematically constructed the KSHV-encoded miRNA-regulated co-expressed protein-protein interaction network (CePPIN), which display the biological knowledge regarding the mechanism of miRNA-regulated KSHV pathogenesis. Then, we investigated the topological parameters for the proteins in CePPIN, especially for those miRNA targets and we found that cellular target genes of KSHV-encoded miRNAs tend to be hubs and bottlenecks in the network. Then the GO and KEGG pathway analysis suggests that miRNA targets are involved in various cellular processes mostly related to immune regulate and cell cycle. Enrichment analysis was also performed to identify the six important functional modules which are proven to be highly related to KSHV pathogenesis. Finally, difference analysis of common targets and specific targets shows that two kinds of targets are different in terms of both topological properties and enriched functions, thus we can extrapolate that the functions of KSHV-encoded miRNAs can be also classified into two generic groups, one can act as functional mimics of some oncogenic human miRNAs which contribute to tumorigenesis and the other can contribute to maintaining viral survival.