Xiong Kai, Shao Li Hong, Zhang Hai Qin, Jin Linlin, Wei Wei, Dong Zhuo, Zhu Yue Quan, Wu Ning, Jin Shun Zi, Xue Li Xiang
Department of Radiation Oncology, Medical Research Center, Peking University Third Hospital, Beijing 100191, P.R. China.
Key Laboratory of Radiobiology, Ministry of Health, Jilin University, Changchun, Jilin 130021, P.R. China.
Oncol Lett. 2018 Mar;15(3):2863-2870. doi: 10.3892/ol.2017.7705. Epub 2017 Dec 28.
Radiotherapy is commonly used to treat lung cancer but may not kill all cancer cells, which may be attributed to the radiotherapy resistance that often occurs in non-small cell lung cancer (NSCLC). At present, the molecular mechanism of radio-resistance remains unclear. Neuropilin 1 (NRP1), a co-receptor for vascular endothelial growth factor (VEGF), was demonstrated to be associated with radio-resistance of NSCLC cells via the VEGF-phosphoinositide 3-kinase-nuclear factor-κB pathway in our previous study. It was hypothesized that certain microRNAs (miRs) may serve crucial functions in radio-sensitivity by regulating NRP1. Bioinformatics predicted that NRP1 was a potential target of miR-9, and this was validated by luciferase reporter assays. Functionally, miR-9-transfected A549 cells exhibited a decreased proliferation rate, increased apoptosis rate and attenuated migratory and invasive abilities. Additionally, a high expression of miR-9 also significantly enhanced the radio-sensitivity of A549 cells and . These data improve understanding of the mechanisms of cell radio-resistance, and suggest that miR-9 may be a molecular target for the prediction of radio-sensitivity in NSCLC.
放射疗法常用于治疗肺癌，但可能无法杀死所有癌细胞，这可能归因于非小细胞肺癌（NSCLC）中经常出现的放射抗性。目前，放射抗性的分子机制仍不清楚。在我们之前的研究中，神经纤毛蛋白1（NRP1）作为血管内皮生长因子（VEGF）的共受体，被证明通过VEGF-磷酸肌醇3-激酶-核因子-κB途径与NSCLC细胞的放射抗性相关。据推测，某些微小RNA（miR）可能通过调节NRP1在放射敏感性中发挥关键作用。生物信息学预测NRP1是miR-9的潜在靶标，荧光素酶报告基因检测验证了这一点。在功能上，转染miR-9的A549细胞增殖率降低，凋亡率增加，迁移和侵袭能力减弱。此外，miR-9的高表达也显著增强了A549细胞的放射敏感性。这些数据增进了对细胞放射抗性机制的理解，并表明miR-9可能是预测NSCLC放射敏感性的分子靶标。
