Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Second Clinical Medical College, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
Biosci Rep. 2019 Sep 13;39(9). doi: 10.1042/BSR20190415. Print 2019 Sep 30.
Resistance to radiotherapy is one of the main causes of treatment failure in patients with nasopharyngeal carcinoma (NPC). Epstein-Barr virus (EBV) infection is an important factor in the pathogenesis of NPC, and EBV-encoded microRNAs (miRNAs) promote NPC progression. However, the role of EBV-encoded miRNAs in the radiosensitivity of NPC remains unclear. Here, we investigated the effects of EBV-miR-BART8-3p on radiotherapy resistance in NPC cells and , and explored the underlying molecular mechanisms. Inhibitors of ataxia telangiectasia mutated (ATM)/ataxia telangiectasia mutated and Rad3-related (ATR) (KU60019 and AZD6738, respectively) were used to examine radiotherapy resistance. We proved that EBV-miR-BART8-3p promoted NPC cell proliferation in response to irradiation and associated with the induction of cell cycle arrest at the G2/M phase, which was a positive factor for the DNA repair after radiation treatment. Besides, EBV-miR-BART8-3p could increase the size of xenograft tumors significantly in nude mice. Treatment with KU60019 or AZD6738 increased the radiosensitivity of NPC by suppressing the expression of p-ATM and p-ATR. The present results indicate that EBV-miR-BART8-3p promotes radioresistance in NPC by modulating the activity of ATM/ATR signaling pathway.
放射治疗抵抗是鼻咽癌（NPC）患者治疗失败的主要原因之一。EB 病毒（EBV）感染是 NPC 发病机制中的一个重要因素，EBV 编码的 microRNAs（miRNAs）促进 NPC 的进展。然而，EBV 编码的 miRNAs 在 NPC 的放射敏感性中的作用尚不清楚。在这里，我们研究了 EBV-miR-BART8-3p 对 NPC 细胞放射抵抗的影响，并探讨了其潜在的分子机制。使用 ATM/ATR（KU60019 和 AZD6738）抑制剂来检测放射抵抗。我们证明 EBV-miR-BART8-3p 促进 NPC 细胞在照射下的增殖，并与细胞周期阻滞在 G2/M 期有关，这是放射治疗后 DNA 修复的一个正因素。此外，EBV-miR-BART8-3p 可以在裸鼠中显著增加异种移植肿瘤的大小。用 KU60019 或 AZD6738 处理可通过抑制 p-ATM 和 p-ATR 的表达来增加 NPC 的放射敏感性。本研究结果表明，EBV-miR-BART8-3p 通过调节 ATM/ATR 信号通路的活性促进 NPC 的放射抵抗。
