Objective:

To discuss the effects of Epstein-Barr virus (EBV)-encoded BamHI A rightward transcript (BART) microRNA (miR-BART6-5p) by targeting Dicer1 on biological properties and radiosensitivity of nasopharyngeal carcinoma (NPC).

Methods:

NPC patients (n = 96) treated with radiotherapy were collected from Jan 2010 to Jan 2011. Real-time quantitative PCR (qRT-PCR) and western blot were carried out to measure the expression of miR-BART6-5p and Dicer1. Dual luciferase reporter gene assay verified that miR-BART6-5p targeted Dicer1. CCK8, wound-healing, Transwell and Annexin-FITC/PI were employed to evaluate the effects of Dicer1 mediated by miR-BART6-5p on biological characteristics of NPC cells. The radiosensitivity of miR-BART6-5p targeting Dicer1 was assessed in vitro and in vivo.

Results:

Increased miR-BART6-5p and decreased Dicer1 were discovered in NPC patients, displaying a close association with T-stage, clinical stage, as well as Pre-DNA of NPC. While elevated Dicer1 and miR-BART6-5p down-regulation in NPC patients were found after effective radiotherapy. Both miR-BART6-5p and Dicer1 were prognostic factors of NPC. Down-regulation of miR-BART6-5p could enhance Dicer1 expression and inhibit NPC cell proliferation, invasion and migration with promoted apoptosis. Clone formation assay also showed miR-BART6-5p down-regulation reduced planting efficiency (PE), which further decreased with the increased dose of irradiation. Injection with miR-BART6-5p inhibitors in nude mice after 6-Gy irradiation contributed to the overexpression of Dicer1 and the inhibition of tumor growth.

Conclusions:

EBV-miR-BART6-5p may target Dicer1 to facilitate proliferation and metastasis of NPC cells and suppress apoptosis, thus being a new target for NPC therapy.

中文翻译：

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EBV-miR-BART6-5p靶向Dicer1对鼻咽癌生物学特性和放射敏感性的影响

客观的：

探讨 Epstein-Barr 病毒 (EBV) 编码的 BamHI A 右向转录本 (BART) microRNA (miR-BART6-5p) 通过靶向Dicer1对鼻咽癌 (NPC) 生物学特性和放射敏感性的影响。

方法：

收集2010年1月至2011年1月接受放射治疗的鼻咽癌患者（n = 96）。进行实时定量PCR（qRT-PCR）和蛋白质印迹以测量miR-BART6-5p和Dicer1的表达。双荧光素酶报告基因检测证实 miR-BART6-5p 靶向Dicer1。采用CCK8、伤口愈合、Transwell和Annexin-FITC/PI评估miR-BART6-5p介导的Dicer1对NPC细胞生物学特性的影响。在体外和体内评估了靶向Dicer1的 miR-BART6-5p 的放射敏感性。

结果：

增加的miR-BART6-5p和降低DICER1在NPC患者被发现后，显示与T-阶段，临床分期，以及NPC的预DNA密切关联。虽然在有效放疗后发现鼻咽癌患者的 Dicer1 和 miR-BART6-5p 下调。miR-BART6-5p 和 Dicer1 都是 NPC 的预后因素。下调 miR-BART6-5p 可增强 Dicer1 表达并抑制 NPC 细胞增殖、侵袭和迁移，促进细胞凋亡。克隆形成试验还显示 miR-BART6-5p 下调降低了种植效率 (PE)，随着照射剂量的增加，种植效率 (PE) 进一步降低。在 6-Gy 照射后在裸鼠中注射 miR-BART6-5p 抑制剂有助于 Dicer1 的过度表达和肿瘤生长的抑制。

结论：

EBV-miR-BART6-5p可能靶向Dicer1促进NPC细胞的增殖和转移并抑制细胞凋亡，从而成为NPC治疗的新靶点。