Department of Stomatology, Jingzhou Central Hospital, The Second Clinical Medical College, Yangtze University, Jingzhou, China.
Department of Otolaryngology, 549615The People's Hospital of Rizhao, Rizhao, China.
Hum Exp Toxicol. 2021 Jun;40(6):977-993. doi: 10.1177/0960327120979020. Epub 2020 Dec 11.
To discuss the effects of Epstein-Barr virus (EBV)-encoded BamHI A rightward transcript (BART) microRNA (miR-BART6-5p) by targeting on biological properties and radiosensitivity of nasopharyngeal carcinoma (NPC).
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 . 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 was assessed and .
Increased miR-BART6-5p and decreased 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.
EBV-miR-BART6-5p may target to facilitate proliferation and metastasis of NPC cells and suppress apoptosis, thus being a new target for NPC therapy.
探讨 Epstein-Barr 病毒（EBV）编码的 BamHI A 右向转录物（BART）microRNA（miR-BART6-5p）通过靶向 对鼻咽癌（NPC）生物学特性和放射敏感性的影响。
收集 2010 年 1 月至 2011 年 1 月接受放疗的 NPC 患者（n=96），采用实时定量 PCR（qRT-PCR）和 Western blot 检测 miR-BART6-5p 和 Dicer1 的表达。双荧光素酶报告基因实验验证 miR-BART6-5p 靶向 。CCK8、划痕愈合、Transwell 和 Annexin-FITC/PI 实验评估 miR-BART6-5p 介导的 Dicer1 对 NPC 细胞生物学特性的影响。评估 miR-BART6-5p 靶向 的放射敏感性。
NPC 患者中发现 miR-BART6-5p 增加， 减少，与 T 分期、临床分期和 NPC 前 DNA 密切相关。而有效放疗后 NPC 患者中发现 miR-BART6-5p 及 Dicer1 高表达下调。miR-BART6-5p 和 Dicer1 都是 NPC 的预后因素。下调 miR-BART6-5p 可增强 Dicer1 的表达，抑制 NPC 细胞的增殖、侵袭和迁移，促进细胞凋亡。克隆形成实验也表明 miR-BART6-5p 下调降低种植效率（PE），随着照射剂量的增加，PE 进一步降低。6-Gy 照射后向裸鼠注射 miR-BART6-5p 抑制剂促进 Dicer1 过表达并抑制肿瘤生长。
EBV-miR-BART6-5p 可能通过靶向 促进 NPC 细胞的增殖和转移，抑制细胞凋亡，从而成为 NPC 治疗的新靶点。
