MicroRNA-9 functions as a tumor suppressor and enhances radio-sensitivity in radio-resistant A549 cells by targeting neuropilin 1.

MicroRNA-9 functions as a tumor suppressor and enhances radio-sensitivity in radio-resistant A549 cells by targeting neuropilin 1.
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MicroRNA-9 作为肿瘤抑制剂发挥作用,并通过靶向神经毡蛋白 1 增强抗辐射 A549 细胞的放射敏感性

DOI:
10.3892/ol.2017.7705
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发表时间:
2018-03
期刊:
影响因子:
2.9
通讯作者:
Xue LX
Xue LX
中科院分区:
医学4区
文献类型:
--
作者:
Xiong K;Shao LH;Zhang HQ;Jin L;Wei W;Dong Z;Zhu YQ;Wu N;Jin SZ;Xue LX

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放射治疗通常用于治疗肺癌,但并不能杀死所有的癌细胞,这可能归因于非小细胞肺癌(NSCLC)经常出现的放射抵抗。目前,辐射抗性的分子机制尚不清楚。NRP1是血管内皮细胞生长因子的辅助受体,在我们先前的研究中,它通过血管内皮生长因子-磷脂酰肌醇-3-激酶-核因子-κB途径与非小细胞肺癌细胞的放射抵抗有关。有人推测,某些microRNAs(MiRs)可能通过调节Nrp1而在辐射敏感性中发挥关键作用。生物信息学预测Nrp1是miR-9的潜在靶点,并通过荧光素酶报告基因分析验证了这一点。在功能上,转miR-9基因的A549细胞的增殖率降低,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细胞在体外和体内的放射敏感性。这些数据加深了对细胞放射抗性机制的理解,并提示miR-9可能是预测非小细胞肺癌放射敏感性的分子靶点。
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 in vitro and in vivo. 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.
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