Ma Huimin, Lian Rong, Wu Zhiyan, Li Xiao, Yu Wenfa, Shang Yun, Guo Xixia
1 Department of Otolaryngology, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, P.R. China.
2 Neonatal Intensive Care Unit, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, P.R. China.
Tumour Biol. 2017 Oct;39(10):1010428317706224. doi: 10.1177/1010428317706224.
Enhancing the sensitivity of laryngeal cells to radiation is crucial for improving the efficacy of laryngeal carcinoma. MicroRNAs are known to play a major role in regulating cellular radiosensitivity. This study was designed to explore the effect and the molecular basis of miR-503 in the radiosensitivity of laryngeal carcinoma cells. Quantitative real-time polymerase chain reaction analysis showed that miR-503 expression was decreased in human laryngeal carcinoma cell lines Hep-2 and TU212, and the downregulation of miR-503 was also observed after irradiation. Upregulation of miR-503 by pre-miR-503 transfection restrained proliferation, promoted progression of Hep-2 and TU212 cells through the cell cycle after irradiation, and sensitized cells to radiation. Dual-Luciferase Reporter Assay verified a direct interaction between miR-503 and the WEE1 messenger RNA 3'-untranslated region. The overexpression of miR-503 significantly decreased WEE1 expression at the messenger RNA and protein levels, whereas the inhibition of miR-503 upregulated the expression of WEE1. WEE1 knockdown by WEE1 small interfering RNA apparently abrogated the inhibitory effect of anti-miR-503 on radiosensitivity. In conclusion, miR-503 could function as an enhancer of radiation responses in laryngeal carcinoma cells by inhibiting WEE1, which may be a potential novel radiosensitizing strategy for laryngeal carcinoma.
提高喉癌细胞对放疗的敏感性对于提高喉癌治疗效果至关重要。已知微小RNA在调节细胞放射敏感性中起主要作用。本研究旨在探讨miR-503对喉癌细胞放射敏感性的影响及其分子基础。定量实时聚合酶链反应分析显示,在人喉癌细胞系Hep-2和TU212中miR-503表达降低,且照射后也观察到miR-503下调。通过pre-miR-503转染上调miR-503可抑制增殖,促进照射后Hep-2和TU212细胞通过细胞周期进程,并使细胞对放疗敏感。双荧光素酶报告基因检测证实miR-503与WEE1信使核糖核酸3'-非翻译区之间存在直接相互作用。miR-503过表达在信使核糖核酸和蛋白质水平显著降低WEE1表达,而抑制miR-503则上调WEE1表达。用WEE1小干扰核糖核酸敲低WEE1明显消除了抗miR-503对放射敏感性的抑制作用。总之,miR-503可通过抑制WEE1发挥喉癌细胞放射反应增强剂的作用,这可能是一种潜在的喉癌新放射增敏策略。