miR-483-5p decreases the radiosensitivity of nasopharyngeal carcinoma cells by targeting DAPK1

Lab Invest. 2019 May;99(5):602-611. doi: 10.1038/s41374-018-0169-6. Epub 2019 Jan 21.

Abstract

Recurrence or metastasis resulting from radioresistance are the main challenges for the treatment of nasopharyngeal carcinoma (NPC). A great deal of evidence supports the role of abnormal expression of miRNAs in radioresistance and malignancy. In some cancers, miR-483-5p is associated with inferior disease-specific survival. Therefore, we investigated the role of miR-483-5p in NPC radiosensitivity and the mechanism by which the miR-483-5p affects the radiosensitivity of NPC cells. In this study, we show that the overexpression of miR-483-5p decreases the radiosensitivity of NPC cells in vitro and in vivo. Mechanistically, miR-483-5p exerts these functions by decreasing radiation-induced apoptosis and DNA damage, and by increasing NPC cell colony formation, via targeting death-associated protein kinase 1 (DAPK1). Finally, our results confirm that the upregulation of miR-483-5p is correlated with advanced clinical stage and inferior overall survival of patients with NPC. These findings provide novel insights into our understanding of the molecular mechanisms underlying therapy failure in NPC. Modulation of miR-483-5p and DAPK1 levels may provide a new approach for increasing the radiosensitivity of these tumors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / genetics
  • Animals
  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Apoptosis / radiation effects
  • Cell Line, Tumor
  • Chemoradiotherapy / methods
  • Death-Associated Protein Kinases / genetics*
  • Death-Associated Protein Kinases / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics*
  • Nasopharyngeal Carcinoma / genetics*
  • Nasopharyngeal Carcinoma / metabolism
  • Nasopharyngeal Carcinoma / therapy
  • Nasopharyngeal Neoplasms / genetics*
  • Nasopharyngeal Neoplasms / metabolism
  • Nasopharyngeal Neoplasms / therapy
  • RNA Interference
  • Radiation Tolerance / genetics*
  • Survival Analysis
  • Xenograft Model Antitumor Assays / methods

Substances

  • 3' Untranslated Regions
  • MIRN483 microRNA, human
  • MicroRNAs
  • DAPK1 protein, human
  • Death-Associated Protein Kinases