Oncomir mir-182-5p enhances radiosensitivity by inhibiting the radiation-induced antioxidant effect through sesn2 in head and neck cancer

Min Ying Lin, Yu Chan Chang, Shan Ying Wang, Muh Hwa Yang, Chih Hsien Chang, Michael Hsiao, Richard N. Kitsis, Yi Jang Lee

Research output: Contribution to journalArticlepeer-review

Abstract

Radiotherapy is routinely used for the treatment of head and neck squamous cell carcinoma (HNSCC). However, the therapeutic efficacy is usually reduced by acquired radioresistance and locoregional recurrence. In this study, The Cancer Genome Atlas (TCGA) analysis showed that radiotherapy upregulated the miR-182/96/183 cluster and that miR-182 was the most significantly upregulated. Overexpression of miR-182-5p enhanced the radiosensitivity of HNSCC cells by in-creasing intracellular reactive oxygen species (ROS) levels, suggesting that expression of the miR-182 family is beneficial for radiotherapy. By intersecting the gene targeting results from three microRNA target prediction databases, we noticed that sestrin2 (SESN2), a molecule resistant to oxidative stress, was involved in 91 genes predicted in all three databases to be directly recognized by miR-182-5p. Knockdown of SESN2 enhanced radiation-induced ROS and cytotoxicity in HNSCC cells. In addition, the radiation-induced expression of SESN2 was repressed by overexpression of miR-182-5p. Reciprocal expression of the miR-182-5p and SESN2 genes was also analyzed in the TCGA database, and a high expression of miR-182-5p combined with a low expression of SESN2 was associated with a better survival rate in patients receiving radiotherapy. Taken together, the current data suggest that miR-182-5p may regulate radiation-induced antioxidant effects and mediate the efficacy of radiotherapy.

Original languageEnglish (US)
Article number1808
JournalAntioxidants
Volume10
Issue number11
DOIs
StatePublished - Nov 2021

Keywords

  • Antioxidant
  • Head and neck squamous cell carcinoma
  • MiR-182-5p
  • MiR-182/96/183 cluster
  • Radioresistance
  • SESN2

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

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