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Lin MY, Chang YC, Wang SY, et al. OncomiR miR-182-5p Enhances Radiosensitivity by Inhibiting the Radiation-Induced Antioxidant Effect through SESN2 in Head and Neck Cancer. Antioxidants (Basel). 2021;10(11)doi: 10.3390/antiox10111808.
Lin, M. Y., Chang, Y. C., Wang, S. Y., Yang, M. H., Chang, C. H., Hsiao, M., Kitsis, R. N., & Lee, Y. J. (2021). OncomiR miR-182-5p Enhances Radiosensitivity by Inhibiting the Radiation-Induced Antioxidant Effect through SESN2 in Head and Neck Cancer. Antioxidants (Basel, Switzerland), 10(11), . https://doi.org/10.3390/antiox10111808
Lin, Min-Ying, et al. "OncomiR miR-182-5p Enhances Radiosensitivity by Inhibiting the Radiation-Induced Antioxidant Effect through SESN2 in Head and Neck Cancer." Antioxidants (Basel, Switzerland) vol. 10,11 (2021). doi: https://doi.org/10.3390/antiox10111808
Lin MY, Chang YC, Wang SY, Yang MH, Chang CH, Hsiao M, Kitsis RN, Lee YJ. OncomiR miR-182-5p Enhances Radiosensitivity by Inhibiting the Radiation-Induced Antioxidant Effect through SESN2 in Head and Neck Cancer. Antioxidants (Basel). 2021 Nov 14;10(11). doi: 10.3390/antiox10111808. PMID: 34829679; PMCID: PMC8614815.
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Antioxidants (Basel). 2021 Nov 14;10(11). doi: 10.3390/antiox10111808.

OncomiR miR-182-5p Enhances Radiosensitivity by Inhibiting the Radiation-Induced Antioxidant Effect through SESN2 in Head and Neck Cancer.

Antioxidants (Basel, Switzerland)

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

Affiliations

  1. Department of Biomedical Imaging and Radiological Sciences, National Yang Ming Chiao Tung University, Taipei Branch, Taipei 112, Taiwan.
  2. Department of Nuclear Medicine, Far Eastern Memorial Hospital, New Taipei City 220, Taiwan.
  3. Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei Branch, Taipei 112, Taiwan.
  4. Division of Medical Oncology, Department of Oncology, Taipei Veterans General Hospital, Taipei 112, Taiwan.
  5. Cancer Progression Research Center, National Yang Ming Chiao Tung University, Taipei Branch, Taipei 112, Taiwan.
  6. Isotope Application Division, Institute of Nuclear Energy Research, Taoyuan 325207, Taiwan.
  7. Genomics Research Center, Academia Sinica, Taipei 11529, Taiwan.
  8. Departments of Medicine (Cardiology) and Cell Biology and Wilf Family Cardiovascular Research Institute, Albert Einstein College of Medicine, New York, NY 10461, USA.

PMID: 34829679 PMCID: PMC8614815 DOI: 10.3390/antiox10111808

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 increasing 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.

Keywords: SESN2; antioxidant; head and neck squamous cell carcinoma; miR-182-5p; miR-182/96/183 cluster; radioresistance

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