Long non-coding RNA KCNQ1OT1 promotes nasopharyngeal carcinoma cell cisplatin resistance via the miR-454/USP47 axis

Abstract

Long non-coding RNAs serve an essential role in drug resistance in various types of cancer, including lung, breast and bladder cancer. The present study aimed to inves- tigate whether KcNQ1 opposite strand/antisense transcript 1 (KcNQ1OT1) was associated with cisplatin (ddP) resistance in nasopharyngeal carcinoma (NPc). KcNQ1OT1, microRNA (miR)-454 and ubiquitin specific peptidase 47 (USP47) expres- sion levels were measured via reverse transcription-quantitative PcR. 5-8F/DDP and SUNE-1/ddP cell viability and chemo- sensitivity were assessed by performing cell counting Kit-8 assays. colony forming and Transwell assays were conducted to assess the effect of the KcNQ1OT1/miR-454/USP47 axis on ddP resistance in NPc cells. The association between miR-454 and KCNQ1OT1 or USP47 was verified via bioinfor- matics analysis, dual-luciferase reporter assays and RIP assays. KCNQ1OT1 and USP47 expression levels were significantly upregulated, whereas miR-454 expression levels were signifi- cantly downregulated in ddP-resistant NPc cells compared with parental NPc cells. KcNQ1OT1 knockdown promoted chemosensitivity in ddP-resistant NPc cells (5-8F/ddP and SUNE-1/DDP), as indicated by significantly decreased cell proliferation, migration and invasion in the short hairpin RNA (sh)KcNQ1OT1 group compared with the sh-negative control (NC) group. Moreover, miR-454 was identified as a target of KCNQ1OT1. KCNQ1OT1 overexpression significantly reversed miR-454 overexpression-mediated effects on NPC cell viability and ddP resistance. Furthermore, the results indi- cated that miR-454 directly targeted USP47. Compared with the shNC group, USP47 knockdown significantly suppressed NPC cell viability and DDP resistance, which was signifi- cantly reversed by co-transfection with miR-454 inhibitor. Furthermore, compared with the shNc group, KcNQ1OT1 knockdown significantly downregulated USP47 expression, which was significantly counteracted by miR-454 knockdown. collectively, the results of the present study indicated that KcNQ1OT1 enhanced ddP resistance in NPc cells via the miR-454/USP47 axis, suggesting a potential therapeutic target for patients with ddP-resistant NPc.