ABSTRACT
Nasopharyngeal carcinoma (NPC) is a prevalent head and neck tumor which has a high mortality rate in Southeast Asia, especially in Southern China. Cancer susceptibility candidate 2 (CASC2) is a newly identified long noncoding RNA (lncRNA) that has been found to play a suppressive role in several types of tumors. However, the expression and functional role of CASC2 in NPC are still unclear. In the present study, using NPC tissues, cells and transplanted mice, we investigated the mechanism of CASC2mediated regulation of NPC. We showed that the CASC2 level is reduced in NPC tissues and cells. CASC2 downregulation promoted proliferation and inhibited apoptotic cell death in NPC cells. In contrast, CASC2 upregulation inhibited proliferation and increased apoptosis. There were putative binding sites of microRNA (miR)18a5p in the promoter of CASC2. The level of miR18a5p was upregulated in NPC tissues and cells. We further confirmed that CASC2 could directly bind with miR18a5p and inhibit miR18a5p expression, using reporter gene and RNA immunoprecipitation assays. miR18a5p suppressed CASC2 upregulationmediated decrease in proliferation and increase in apoptotic cell death. Bioinformatics predicted the putative binding site of miR18a5p in the 3' untranslated region of Cterminal binding protein interacting protein (CtIP)/RBBP8. It was further confirmed that miR18a5p could directly bind with RBBP8 and inhibit RBBP8 expression. Downregulation of RBBP8 inhibited the antimiR18a5pmediated increase in apoptosis and decrease in proliferation. Downregulation of CASC2 increased tumor growth, increased the level of miR18a5p and decreased RBBP8 expression in vivo. In summary, CASC2 regulates NPC malignancy through modulation of RBBP8 via sponging miR18a5p. Our findings highlight the CASC2/miR18a5p/RBBP8 axis in NPC pathogenesis and provide new biomarkers and potential targets for the therapy of NPC.
