Oncogenic KSHV-encoded interferon regulatory factor upregulates HMGB2 and CMPK1 expression to promote cell invasion by disrupting a complex lncRNA-OIP5-AS1/miR-218-5p network

• DOI: 10.1371/journal.ppat.1007578
• Publication Date: 2019-01-30T20:09:11Z
• Authors: Wan Li; Qingxia Wang; Qi Feng; Fei Wang; Qin Yan; Shou-Jiang Gao; Chun Lu
• Keywords: Competing Endogenous RNA; Kaposi's sarcoma-associated herpesvirus; DNMT1

Kaposi's sarcoma (KS), a highly disseminated tumor of hyperproliferative spindle endothelial cells, is the most common AIDS-associated malignancy caused by infection sarcoma-associated herpesvirus (KSHV). KSHV-encoded viral interferon regulatory factor 1 (vIRF1) oncogene but its role in KSHV-induced invasiveness and motility remains unknown. Here, we report that vIRF1 promotes cell migration, invasion proliferation down-regulating miR-218-5p to relieve suppression downstream targets high mobility group box 2 (HMGB2) cytidine/uridine monophosphate kinase (CMPK1). Mechanistically, inhibits p53 function increase expression DNA methyltransferase (DNMT1) methylation promoter pre-miR-218-1, precursor miR-218-5p, increases long non-coding RNA OIP5 antisense (lnc-OIP5-AS1), which acts as competing endogenous (ceRNA) inhibit reduce stability. Moreover, lnc-OIP5-AS1 pre-miR-218-1 promoter. Finally, deletion from KSHV genome reduces level lnc-OIP5-AS1, invasion. Together, these results define novel complex lnc-OIP5-AS1/miR-218-5p network hijacked promote tumors.