Zhang Fei, Duan Chuanxin, Yin Shucheng, Tian Ying
Department of Otolaryngology, Maternal and Child Health Care Hospital of Hubei Province and Women and Children's Hospital of Hubei Province, Wuhan 430070, People's Republic of China.
Department of Otorhinolaryngology-Head and Neck Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, People's Republic of China.
Cancer Manag Res. 2020 Jun 9;12:4335-4346. doi: 10.2147/CMAR.S253504. eCollection 2020.
Epithelial-mesenchymal transition (EMT) is a major actor modulating the metastasis of nasopharyngeal carcinoma (NPC). Increasing evidence indicates that microRNAs (miRs) are the important regulators of EMT program. However, the potential roles and underlying mechanisms of miR‑379-5p in regulating EMT of NPC cells remain unclear.
miR-379-5p expression levels in human NPC tissues and cell lines were detected via quantitative real-time PCR (qRT-PCR). Then, the correlations between miR-379-5p expression in NPC tissues and clinicopathologic features and patients' prognosis were analyzed. The effect of miR-379-5p on the expression of EMT markers in NPC cells was evaluated by Western blot and qRT-PCR. NPC cells' migration and invasion were evaluated in vitro by Transwell migration and invasion assays, respectively. The target of miR-379-5p was predicted with three publicly available databases and further validated with dual-luciferase reporter assay, qRT-PCR, and Western blot.
The expression of miR-379-5p was significantly decreased in NPC tissues, and its low expression was significantly associated with multiple unfavorable clinicopathological factors and poor prognosis of NPC patients. Meanwhile, miR-379-5p was downregulated in NPC cell lines, and its exotic expression inhibited EMT to reduce the migration and invasion of NPC cells. Furthermore, Y-box binding protein 1 (YBX1) was identified and validated as a direct target of miR-379-5p, and restoring YBX1 expression could reverse the inhibitive effect of miR-379-5p on NPC cell EMT, migration and invasion.
Taken together, our findings indicate that miR-379-5p inhibits the EMT of NPC cells to reduce their migration and invasion abilities by post-transcriptionally suppressing YBX1 expression, providing a novel potential treatment target for NPC patients.
上皮-间质转化（EMT）是调节鼻咽癌（NPC）转移的主要因素。越来越多的证据表明，微小RNA（miR）是EMT程序的重要调节因子。然而，miR-379-5p在调节NPC细胞EMT中的潜在作用和潜在机制仍不清楚。
通过定量实时聚合酶链反应（qRT-PCR）检测人NPC组织和细胞系中miR-379-5p的表达水平。然后，分析NPC组织中miR-379-5p表达与临床病理特征及患者预后的相关性。通过蛋白质免疫印迹法和qRT-PCR评估miR-379-5p对NPC细胞中EMT标志物表达的影响。分别通过Transwell迁移和侵袭实验在体外评估NPC细胞的迁移和侵袭能力。用三个公开可用的数据库预测miR-379-5p的靶标，并通过双荧光素酶报告基因实验、qRT-PCR和蛋白质免疫印迹法进一步验证。
miR-379-5p在NPC组织中的表达显著降低，其低表达与多种不利的临床病理因素及NPC患者的不良预后显著相关。同时，miR-379-5p在NPC细胞系中表达下调，其过表达抑制EMT以减少NPC细胞的迁移和侵袭。此外，Y盒结合蛋白1（YBX1）被鉴定并验证为miR-379-5p的直接靶标，恢复YBX1表达可逆转miR-379-5p对NPC细胞EMT、迁移和侵袭的抑制作用。
综上所述，我们的研究结果表明，miR-379-5p通过转录后抑制YBX1表达来抑制NPC细胞的EMT，从而降低其迁移和侵袭能力，为NPC患者提供了一个新的潜在治疗靶点。
