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

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...

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Autores principales:	Min-Ying Lin, Yu-Chan Chang, Shan-Ying Wang, Muh-Hwa Yang, Chih-Hsien Chang, Michael Hsiao, Richard N. Kitsis, Yi-Jang Lee
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	miR-182/96/183 cluster miR-182-5p head and neck squamous cell carcinoma radioresistance antioxidant SESN2 Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/69ae8dd481bc407dac3e7ebc668a5e95
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spelling	oai:doaj.org-article:69ae8dd481bc407dac3e7ebc668a5e952021-11-25T16:28:53ZOncomiR miR-182-5p Enhances Radiosensitivity by Inhibiting the Radiation-Induced Antioxidant Effect through SESN2 in Head and Neck Cancer10.3390/antiox101118082076-3921https://doaj.org/article/69ae8dd481bc407dac3e7ebc668a5e952021-11-01T00:00:00Zhttps://www.mdpi.com/2076-3921/10/11/1808https://doaj.org/toc/2076-3921Radiotherapy 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.Min-Ying LinYu-Chan ChangShan-Ying WangMuh-Hwa YangChih-Hsien ChangMichael HsiaoRichard N. KitsisYi-Jang LeeMDPI AGarticlemiR-182/96/183 clustermiR-182-5phead and neck squamous cell carcinomaradioresistanceantioxidantSESN2Therapeutics. PharmacologyRM1-950ENAntioxidants, Vol 10, Iss 1808, p 1808 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	miR-182/96/183 cluster miR-182-5p head and neck squamous cell carcinoma radioresistance antioxidant SESN2 Therapeutics. Pharmacology RM1-950
spellingShingle	miR-182/96/183 cluster miR-182-5p head and neck squamous cell carcinoma radioresistance antioxidant SESN2 Therapeutics. Pharmacology RM1-950 Min-Ying Lin Yu-Chan Chang Shan-Ying Wang Muh-Hwa Yang Chih-Hsien Chang Michael Hsiao Richard N. Kitsis Yi-Jang Lee OncomiR miR-182-5p Enhances Radiosensitivity by Inhibiting the Radiation-Induced Antioxidant Effect through SESN2 in Head and Neck Cancer
description	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.
format	article
author	Min-Ying Lin Yu-Chan Chang Shan-Ying Wang Muh-Hwa Yang Chih-Hsien Chang Michael Hsiao Richard N. Kitsis Yi-Jang Lee
author_facet	Min-Ying Lin Yu-Chan Chang Shan-Ying Wang Muh-Hwa Yang Chih-Hsien Chang Michael Hsiao Richard N. Kitsis Yi-Jang Lee
author_sort	Min-Ying Lin
title	OncomiR miR-182-5p Enhances Radiosensitivity by Inhibiting the Radiation-Induced Antioxidant Effect through SESN2 in Head and Neck Cancer
title_short	OncomiR miR-182-5p Enhances Radiosensitivity by Inhibiting the Radiation-Induced Antioxidant Effect through SESN2 in Head and Neck Cancer
title_full	OncomiR miR-182-5p Enhances Radiosensitivity by Inhibiting the Radiation-Induced Antioxidant Effect through SESN2 in Head and Neck Cancer
title_fullStr	OncomiR miR-182-5p Enhances Radiosensitivity by Inhibiting the Radiation-Induced Antioxidant Effect through SESN2 in Head and Neck Cancer
title_full_unstemmed	OncomiR miR-182-5p Enhances Radiosensitivity by Inhibiting the Radiation-Induced Antioxidant Effect through SESN2 in Head and Neck Cancer
title_sort	oncomir mir-182-5p enhances radiosensitivity by inhibiting the radiation-induced antioxidant effect through sesn2 in head and neck cancer
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/69ae8dd481bc407dac3e7ebc668a5e95
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OncomiR miR-182-5p Enhances Radiosensitivity by Inhibiting the Radiation-Induced Antioxidant Effect through SESN2 in Head and Neck Cancer

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