OncomiR miR-182-5p Enhances Radiosensitivity by Inhibiting the Radiation-Induced Antioxidant Effect through SESN2 in Head and Neck Cancer
| Autor: | Yu Chan Chang, Min Ying Lin, Michael Hsiao, Muh Hwa Yang, Shan Ying Wang, Chih Hsien Chang, Yi Jang Lee, Richard N. Kitsis |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
antioxidant
Physiology medicine.medical_treatment Clinical Biochemistry miR-182-5p RM1-950 medicine.disease_cause head and neck squamous cell carcinoma Biochemistry Article Radioresistance microRNA Medicine Radiosensitivity miR-182/96/183 cluster SESN2 Molecular Biology Gene knockdown business.industry Cell Biology Oncomir medicine.disease Head and neck squamous-cell carcinoma Radiation therapy radioresistance Cancer research Therapeutics. Pharmacology business Oxidative stress |
| Zdroj: | Antioxidants Antioxidants, Vol 10, Iss 1808, p 1808 (2021) Volume 10 Issue 11 |
| ISSN: | 2076-3921 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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