Nasopharyngeal Cancer

KCNQ1OT1[LncRNA]

miR-454[miRNA]

USP47[mRNA]

NPC cells (5-8F/DDP and SUNE-1/DDP)

Homo sapiens (human)

Int J Mol Med. 2021 Apr;47(4):54. doi: 10.3892/ijmm.2021.4887. Epub 2021 Feb 12.

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

Dual-luciferase reporter assay;RIP assay;Luciferase reporter assay;

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 investigate 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) expression levels were measured via reverse transcription-quantitative PCR. 5-8F/DDP and SUNE-1/DDP cell viability and chemosensitivity 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 bioinformatics analysis, dual-luciferase reporter assays and RIP assays. KCNQ1OT1 and USP47 expression levels were significantly upregulated, whereas miR-454 expression levels were significantly 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 indicated that miR-454 directly targeted USP47. Compared with the shNC group, USP47 knockdown significantly suppressed NPC cell viability and DDP resistance, which was significantly 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.