Department of Otolaryngology Head & Neck Surgery, Shanghai Ninth People's Hospital, School of Medicine, Shanghai JiaoTong University, Shanghai, 200011, China; Ear Institute, Shanghai JiaoTong University, School of Medicine, Shanghai, 200011, China; Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, 200011, China.
Department of Otolaryngology Head & Neck Surgery, Shanghai Ninth People's Hospital, School of Medicine, Shanghai JiaoTong University, Shanghai, 200011, China; Ear Institute, Shanghai JiaoTong University, School of Medicine, Shanghai, 200011, China; Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, 200011, China.
Mol Cell Probes. 2020 Oct;53:101597. doi: 10.1016/j.mcp.2020.101597. Epub 2020 May 12.
Chemoresistance to cisplatin (DDP) has become a dominating obstacle to the successful treatment of nasopharyngeal carcinoma (NPC). Recently, accumulating data support the tenet that microRNAs (miRNAs) function as new crucial regulators of diverse biological processes, including chemoresistance. In this study, the miRNA expression profiles in NPC were first analyzed using miRNA microarray dataset. miR-1278 was identified as the most decreased miRNA in NPC tissues. We then validated that miR-1278 was significantly down-regulated in NPC tissues and cell lines. Moreover, decreased miR-1278 was strongly associated with worse overall survival and poor chemotherapy response. Gain-of-function experiments showed that overexpression of miR-1278 dramatically sensitized NPC cells to DDP and reduced autophagy. Mechanistically, ATG2B was identified as a target gene of miR-1278. More importantly, ATG2B overexpression reversed miR-1278-induced suppression of autophagy and DDP resistance. Taken together, our results suggested that miR-1278 inhibited the DDP resistance of NPC cells and autophagy through targeting ATG2B. miR-1278 might function as a novel therapeutic target in NPC treatment.
顺铂耐药性（DDP）已成为鼻咽癌（NPC）成功治疗的主要障碍。最近，越来越多的数据支持一个观点，即 microRNAs（miRNAs）作为多种生物过程的新的关键调节剂发挥作用，包括耐药性。在这项研究中，首先使用 miRNA 微阵列数据集分析 NPC 的 miRNA 表达谱。miR-1278 被鉴定为 NPC 组织中降低最显著的 miRNA。然后我们验证了 miR-1278 在 NPC 组织和细胞系中显著下调。此外，miR-1278 的下调与总生存期较差和化疗反应不良密切相关。功能获得实验表明，miR-1278 的过表达可显著增加 NPC 细胞对 DDP 的敏感性并减少自噬。在机制上，鉴定出 ATG2B 是 miR-1278 的靶基因。更重要的是，ATG2B 的过表达逆转了 miR-1278 诱导的自噬和 DDP 耐药性抑制。总之，我们的研究结果表明，miR-1278 通过靶向 ATG2B 抑制 NPC 细胞的 DDP 耐药性和自噬。miR-1278 可能是 NPC 治疗中的一个新的治疗靶点。
