Emerging evidence suggests long non-coding RNA (lncRNA) could sponge microRNAs (miRs) and monitor gene expression. In this study, we intended to search the network involving lncRNA MINCR/miR-223/ZEB1 in nasopharyngeal carcinoma (NPC) cell radiosensitivity. MINCR expression in NPC tissues, precancerous lesions and chronic nasopharyngeal mucosal inflammation tissues, and in NP460, CNE2 and CNE2R cells was detected. The associations between MINCR expression and prognosis and radiotherapy efficacy of NPC patients were evaluated. The interactions among MINCR, miR-223 and ZEB1 were verified via dual luciferase reporter gene assay, RNA pull-down and FISH assays. The gain- and loss-of-functions were performed to explore their effects on NPC cell viability, apoptosis and radiosensitivity. Levels of MINCR, miR-223, ZEB1, and AKT/PI3K-related proteins were detected after different treatments. An in vivo analysis was carried out in nude mice. Consequently, MINCR was upregulated in NPC, and linked with worse prognosis and radiotherapy efficacy. MINCR intervention weakened NPC cell radioresistance. MINCR sponged miR-223 to regulate ZEB1. Inactivating AKT eliminated the increased radioresistance of CNE2 cells induced by overexpressing MINCR. Briefly, MINCR diminished NPC cell radiosensitivity by sponging miR-223, increasing ZEB1 and activating the AKT/PI3K axis. This study may offer novel insight for NPC treatment.
Keywords: AKT/PI3K signaling pathway; Nasopharyngeal carcinoma; ZEB1; long non-coding RNA MINCR; microRNA-223; radioresistance.