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微小RNA-138-5p通过靶向真核翻译起始因子4E结合蛋白1(EIF4EBP1)来控制鼻咽癌对放疗的敏感性。

MicroRNA-138-5p controls sensitivity of nasopharyngeal carcinoma to radiation by targeting EIF4EBP1.

作者信息

Gao Wei, Lam Jacky Wei Kei, Li John Zeng-Hong, Chen Si-Qi, Tsang Raymond King-Yin, Chan Jimmy Yu-Wai, Wong Thian-Sze

机构信息

Department of Surgery, The University of Hong Kong, Hong Kong, SAR, P.R. China.

出版信息

Oncol Rep. 2017 Feb;37(2):913-920. doi: 10.3892/or.2017.5354. Epub 2017 Jan 4.

DOI:10.3892/or.2017.5354
PMID:28075468
Abstract

Radiation therapy is the standard treatment for primary nasopharyngeal carcinoma (NPC). MicroRNA regulates cancer responsiveness to radiation therapy by controlling the genes involved in radiation responses. Recent studies suggested that downregulation of microRNA-138-5p was clinically significant in NPC. Here, we evaluated the effect of miR-138-5p on radiosensitivity of NPC cells and explored the underlying mechanisms by identifying its target gene that impacted sensitivity to radiation. Our results revealed that overexpression of miR-138-5p reduced the ability to form colonies, inhibited proliferation, and enhanced radiation-induced DNA damage and autophagy in NPC cells upon radiation treatment. By integrating predicted targets with the transcripts downregulated by miR-138-5p, EIF4EBP1 was identified to be a target gene of miR-138-5p. Results from luciferase reporter assay demonstrated that miR-138-5p downregulated the expression of EIF4EBP1 by binding to the 3'-UTR. Silence of EIF4EBP1 enhanced radiosensitivity of NPC cells as evidenced by reduced ability to form colonies after radiation exposure. In summary, our results indicated that miR-138-5p enhanced radiosensitivity of NPC cells by targeting EIF4EBP1. Further studies are warranted to investigate the potential use of miR-138-5p in the clinical management and treatment prediction of NPC patients.

摘要

放射治疗是鼻咽癌(NPC)的标准治疗方法。微小RNA通过控制参与放射反应的基因来调节癌症对放射治疗的反应。最近的研究表明,微小RNA-138-5p的下调在鼻咽癌中具有临床意义。在此,我们评估了miR-138-5p对NPC细胞放射敏感性的影响,并通过鉴定其影响放射敏感性的靶基因来探索潜在机制。我们的结果显示,miR-138-5p的过表达降低了NPC细胞的集落形成能力,抑制了增殖,并增强了放射治疗后放射诱导的DNA损伤和自噬。通过将预测的靶标与miR-138-5p下调的转录本整合,确定EIF4EBP1是miR-138-5p的靶基因。荧光素酶报告基因检测结果表明,miR-138-5p通过与3'-UTR结合下调EIF4EBP1的表达。EIF4EBP1的沉默增强了NPC细胞的放射敏感性,放射暴露后集落形成能力降低证明了这一点。总之,我们的结果表明,miR-138-5p通过靶向EIF4EBP1增强了NPC细胞的放射敏感性。有必要进一步研究miR-138-5p在NPC患者临床管理和治疗预测中的潜在用途。

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