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

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

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 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.

Keywords: KCNQ1 opposite strand/antisense transcript 1; microRNA‑454; ubiquitin specific peptidase 47; nasopharyngeal carcinoma; cisplatin resistance.

MeSH terms

  • Blotting, Western
  • Cell Line
  • Cisplatin / pharmacology
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Nasopharyngeal Carcinoma / genetics
  • Nasopharyngeal Carcinoma / metabolism*
  • Potassium Channels, Voltage-Gated / genetics
  • Potassium Channels, Voltage-Gated / metabolism
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Ubiquitin Thiolesterase / genetics
  • Ubiquitin Thiolesterase / metabolism
  • Ubiquitin-Specific Proteases / genetics
  • Ubiquitin-Specific Proteases / metabolism

Substances

  • KCNQ1OT1 long non-coding RNA, human
  • Potassium Channels, Voltage-Gated
  • RNA, Long Noncoding
  • USP47 protein, human
  • Ubiquitin Thiolesterase
  • Ubiquitin-Specific Proteases
  • Cisplatin