miR-4270 Modulates the Irradiation-Sensitivity of Nasopharyngeal Carcinoma Cells through Modulation of p53 in Vivo

Tohoku J Exp Med. 2021 Jun;254(2):63-70. doi: 10.1620/tjem.254.63.

Abstract

The lowered sensitivity to irradiation considerably impacted on the prognosis of nasopharyngeal carcinoma treatments. This study aimed to explore the functions of miR-4270 in nasopharyngeal carcinoma. Bioinformatic analysis was performed online accessing GSE139164 dataset to screen the top 30 differential microRNAs in nasopharyngeal carcinoma patients with radio-sensitivity. Cancer cell lines, 6-10B and 5-8F, were cultured and measured for expression of miR-4270 and TP53 (the gene of the tumor suppressor protein p53) with the normal nasopharyngeal epithelial cells as a control. The miR-4270 expression was regulated in cells via the introduction of miR-4270 inhibitor or mimic in different concentrations (25, 50, 100 nmol/L). Targetscan predicted the target of miR-4270 and the bindings while luciferase was used to confirm this. CCK8 methods were used to evaluate the irradiation sensitivity of the cells after exposure to increasing X-Ray irradiation. RT-PCR detected the RNA expression and Western blot examined the protein expression of p53. Flow cytometry detected the cell apoptosis rates respectively. miR-4270 is among the top differential microRNAs between the radio-sensitive and -resistant patients. In vivo, miR-4270 expression was lower in cancer cell lines. The inhibition of miR-4270 raised the cell sensitivity to irradiation. miR-4270 negatively mediated TP53 and targeted TP53. Additionally, p53 increased cell sensitivity to irradiation and modulated by miR-4270 in nasopharyngeal carcinoma cells. In conclusion, this study first reports that miR-4270 is lower in the radio-sensitive patients and modulated the irradiation-sensitivity of nasopharyngeal carcinoma cells through modulation of p53 in vivo.

Keywords: miR-4270; nasopharyngeal carcinoma; p53; radio-sensitivity.

MeSH terms

  • Cell Line, Tumor
  • Cell Proliferation
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MicroRNAs / genetics*
  • Nasopharyngeal Carcinoma* / genetics
  • Nasopharyngeal Carcinoma* / radiotherapy
  • Nasopharyngeal Neoplasms* / genetics
  • Nasopharyngeal Neoplasms* / radiotherapy
  • Tumor Suppressor Protein p53 / genetics*

Substances

  • MicroRNAs
  • TP53 protein, human
  • Tumor Suppressor Protein p53