Department of Otorhinolaryngology Head and Neck Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, PR China.
Department of Cardiology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin 150006, PR China.
Auris Nasus Larynx. 2020 Aug;47(4):632-642. doi: 10.1016/j.anl.2019.12.007. Epub 2020 Jan 10.
MiR-506 has been reported to be associated with multiple malignancies, but its roles in nasopharyngeal cancer (NPC) are not fully understood. Our objective is to demonstrate its effects on NPC and the underlying mechanisms.
Totally fifteen pairs of NPC and adjacent non-tumorous tissues were collected for the detection of miR-506 and enhancer of zeste homolog 2 (EZH2) expression. Dual luciferase reporter assay was employed for verifying the relationship between miR-506 and EZH2. The flow cytometry and MTT assays were employed to explore the effects of miR-506 and EZH2 on the cell apoptosis and proliferation, respectively. Wound closure and transwell assays were used to evaluate the cell migration and invasion abilities. Western blotting or RT-qPCR assays were applied to detect the alterations of miR-506, EZH2 and epithelial-mesenchymal transition (EMT)-related markers. Morphological changes of cells with EMT were assessed by light microscopy.
MiR-506 was significantly decreased and EZH2 was obviously increased in NPC tissues. Overexpression of miR-506 decreased the EZH2 level, promoted apoptosis, inhibited proliferation, invasion and migration of NPC cells. Accordingly, miR-506 overexpression attenuated EMT process of NPC cells as demonstrated by the alterations of EMT-related markers and the morphological changes. In addition, the luciferase assay proved that miR-506 directly targeted EZH2. Furthermore, the overexpression of EZH2 reversed the tumor-suppressive effects induced by miR-506 mimics.
MiR-506 acted as a tumor suppressor to promote apoptosis and inhibit invasion and migration via directly targeting EZH2. MiR-506 can be a candidate target for gene therapy against NPC.
已有研究表明 miR-506 与多种恶性肿瘤相关，但 miR-506 在鼻咽癌（NPC）中的作用尚不完全清楚。本研究旨在探讨 miR-506 对 NPC 的影响及其作用机制。
收集 15 对 NPC 组织及其癌旁正常组织，检测 miR-506 和增强子结合抑制因子 2（EZH2）的表达。双荧光素酶报告基因实验验证 miR-506 与 EZH2 的靶向关系。流式细胞术和 MTT 实验分别检测 miR-506 和 EZH2 对 NPC 细胞凋亡和增殖的影响。划痕愈合和 Transwell 实验检测 miR-506 和 EZH2 对 NPC 细胞迁移和侵袭的影响。Western blot 或 RT-qPCR 实验检测 miR-506、EZH2 及上皮间质转化（EMT）相关标志物的变化。通过光镜观察 EMT 过程中细胞形态的变化。
与癌旁正常组织相比，miR-506 在 NPC 组织中表达下调，EZH2 表达上调。过表达 miR-506 可降低 EZH2 水平，促进 NPC 细胞凋亡，抑制其增殖、侵袭和迁移。过表达 miR-506 还可减弱 NPC 细胞 EMT 过程，表现为 EMT 相关标志物表达和细胞形态的改变。荧光素酶报告基因实验证实 miR-506 可直接靶向 EZH2。此外，过表达 EZH2 可逆转 miR-506 模拟物诱导的肿瘤抑制作用。
miR-506 通过靶向 EZH2 发挥抑癌作用，促进 NPC 细胞凋亡，抑制其侵袭和迁移。miR-506 可能成为 NPC 基因治疗的候选靶点。
