miR‑182‑5p contributes to radioresistance in nasopharyngeal carcinoma by regulating BNIP3 expression

Mol Med Rep. 2021 Feb;23(2):130. doi: 10.3892/mmr.2020.11769. Epub 2020 Dec 14.

Abstract

Radioresistance is the primary roadblock limiting the success of treatment of nasopharyngeal carcinoma (NPC). microRNA (miRNA/miR)‑182‑5p has been reported to affect the sensitivity of cancer cells to irradiation; however, the role of miR‑182‑5p in NPC has not been assessed. The aim of the present study was to investigate the contribution of miR‑182‑5p to the radioresistance of NPC cells. The key mRNA and miRNA involved in NPC radioresistance were identified using bioinformatics analysis. The two cell lines used in the present study were 5‑8F cells (radio‑sensitive) and 5‑8F‑R cells (radioresistant). A dual‑luciferase reporter assay system was used to validate the binding between BCL2/adenovirus E1B 19 kDa protein‑interacting protein 3 (BNIP3) mRNA and miR‑182‑5p. Reverse transcription‑quantitative PCR and western blotting were used to determine the RNA and protein expression levels. To obtain a deeper insight into the effects of the BNIP3/miR‑182‑5p axis on NPC radioresistance, Cell Counting Kit‑8, wound healing, Transwell invasion and colony formation assays, as well as flow cytometry analysis were performed. The results showed that miR‑182‑5p and BNIP3 were up and downregulated, respectively, in 5‑8F‑R cells. BNIP3 was also confirmed to be the target of miR‑182‑5p, and miR‑182‑5p reversed the inhibitory effect of BNIP3 in 5‑8F‑R cells. The cellular experiments showed that upregulation of BNIP3 not only inhibited cell proliferation, viability, invasion and migration, but also promoted the apoptosis of 5‑8F‑R cells. However, the effects of BNIP3 were attenuated by the simultaneous upregulation of miR‑182‑5p. Thus, through downregulation of BNIP3, miR‑182‑5p contributed to radiation resistance of NPC cells.

Keywords: microRNA‑182‑5p; BCL2/adenovirus E1B 19 kDa protein‑interacting protein 3; nasopharyngeal carcinoma; radioresistance.

MeSH terms

  • 3' Untranslated Regions
  • Apoptosis / genetics
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Cell Survival / genetics
  • Computational Biology
  • Databases, Genetic
  • Down-Regulation
  • Forkhead Transcription Factors / metabolism
  • Gene Expression Regulation, Neoplastic / genetics
  • Gene Expression Regulation, Neoplastic / radiation effects
  • Humans
  • Kaplan-Meier Estimate
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • MicroRNAs / genetics*
  • MicroRNAs / radiation effects*
  • Nasopharyngeal Carcinoma / genetics*
  • Nasopharyngeal Carcinoma / metabolism
  • Nasopharyngeal Carcinoma / pathology
  • Nasopharyngeal Carcinoma / radiotherapy
  • Nasopharyngeal Neoplasms / genetics*
  • Nasopharyngeal Neoplasms / metabolism
  • Nasopharyngeal Neoplasms / pathology
  • Nasopharyngeal Neoplasms / radiotherapy
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • RNA, Messenger / metabolism
  • Radiation Tolerance / genetics*
  • Signal Transduction
  • Up-Regulation

Substances

  • 3' Untranslated Regions
  • BNIP3 protein, human
  • Forkhead Transcription Factors
  • Membrane Proteins
  • MicroRNAs
  • Mirn182 microRNA, human
  • Proto-Oncogene Proteins
  • RNA, Messenger