College of Chemistry, Sichuan University, Chengdu, 610064, P.R. China.
Department of Editor, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, 610072, P.R. China.
Sci Rep. 2017 Jun 9;7(1):3159. doi: 10.1038/s41598-017-03462-w.
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.
卡波氏肉瘤相关疱疹病毒（KSHV）是卡波氏肉瘤、原发性渗出性淋巴瘤和多中心卡斯特曼病等的病因。在这项研究中，我们首先系统地构建了 KSHV 编码 miRNA 调控的共表达蛋白-蛋白相互作用网络（CePPIN），该网络展示了 miRNA 调控 KSHV 发病机制的生物学知识。然后，我们研究了 CePPIN 中蛋白质的拓扑参数，特别是 miRNA 靶标，我们发现 KSHV 编码 miRNA 的细胞靶基因往往是网络中的枢纽和瓶颈。GO 和 KEGG 通路分析表明，miRNA 靶标参与了与免疫调节和细胞周期相关的各种细胞过程。富集分析也被用来识别六个重要的功能模块，这些模块被证明与 KSHV 发病机制高度相关。最后，共同靶标和特定靶标的差异分析表明，两种靶标在拓扑性质和富集功能上存在差异，因此我们可以推断，KSHV 编码 miRNA 的功能也可以分为两类，一类可以作为一些致癌人类 miRNA 的功能模拟物，有助于肿瘤发生，另一类可以有助于病毒的存活。
