MicroRNA-138-5p controls sensitivity of nasopharyngeal carcinoma to radiation by targeting EIF4EBP1

Wei Gao, Jacky Wei Kei Lam, John Zeng Hong Li, Si Qi Chen, Raymond King Yin Tsang, Jimmy Yu Wai Chan, Thian Sze Wong*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

Radiation therapy is the standard treatment for primary nasopharyngeal carcinoma (NPC). MicroRNA regulates cancer responsiveness to radiation therapy by controlling the genes involved in radiation responses. Recent studies suggested that downregulation of microRNA-138-5p was clinically significant in NPC. Here, we evaluated the effect of miR-138-5p on radiosensitivity of NPC cells and explored the underlying mechanisms by identifying its target gene that impacted sensitivity to radiation. Our results revealed that overexpression of miR-138-5p reduced the ability to form colonies, inhibited proliferation, and enhanced radiation-induced DNA damage and autophagy in NPC cells upon radiation treatment. By integrating predicted targets with the transcripts downregulated by miR-138-5p, EIF4EBP1 was identified to be a target gene of miR-138-5p. Results from luciferase reporter assay demonstrated that miR-138-5p downregulated the expression of EIF4EBP1 by binding to the 3'-UTR. Silence of EIF4EBP1 enhanced radiosensitivity of NPC cells as evidenced by reduced ability to form colonies after radiation exposure. In summary, our results indicated that miR-138-5p enhanced radiosensitivity of NPC cells by targeting EIF4EBP1. Further studies are warranted to investigate the potential use of miR- 138-5p in the clinical management and treatment prediction of NPC patients.

Original languageEnglish
Pages (from-to)913-920
Number of pages8
JournalOncology Reports
Volume37
Issue number2
DOIs
StatePublished - Feb 2017
Externally publishedYes

Keywords

  • DNA double-strand breaks
  • EIF4EBP1
  • Nasopharyngeal carcinoma
  • Radiation sensitivity
  • microRNA-138-5p

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