miR-184 Inhibits Tumor Invasion, Migration and Metastasis in Nasopharyngeal Carcinoma by Targeting Notch2
miR-184 Inhibits Tumor Invasion, Migration and Metastasis in Nasopharyngeal Carcinoma by Targeting Notch2
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miR-184通过靶向Notch2抑制鼻咽癌的肿瘤侵袭、迁移和转移。
DOI：
10.1159/000493459
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发表时间：
2018-01-01
影响因子：
--
通讯作者：
Yin, Li
中科院分区：
文献类型：
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作者：
Zhu, Hong-Ming;Jiang, Xue-Song;Yin, Li
背景/目标：最近的一项研究发现，失调的microRNA-184（miR-184）参与了鼻咽癌（NPC）的增殖和生存。本研究旨在探讨鼻咽癌细胞侵袭、迁移和转移的具体机制。方法：采用定量逆转录聚合酶链反应（qRT-PCR）和蛋白质印迹法检测miR-184和Notch 2的表达水平。随后分别使用体外细胞侵袭和伤口愈合测定来检查NPC细胞侵袭和迁移。采用microRNA（miRNA）靶基因预测数据库和双荧光素酶报告基因分析法验证miR-184的靶基因。结果：miR-184在鼻咽癌细胞系中表达下调。miR-184抑制剂增加了侵袭NPC细胞的数量，而miR-184模拟物抑制了此类细胞的侵袭能力。在抗miR-184组中，E-cadherin的蛋白水平降低，而N-cadherin和vimentin的蛋白水平升高。这一结果表明miR-184通过调节EMT进程抑制NPC细胞的侵袭和转移。miRNA靶基因预测数据库表明Notch 2有可能成为miR-184的直接靶基因。双荧光素酶报告基因检测的结果验证了这一观点。值得注意的是，shRNANotch 2抑制了NPC细胞中的EMT，并部分消除了miR-184对EMT进展的抑制作用。结论：miR-184是一种靶向Notch 2的抑瘤miRNA，可抑制鼻咽癌的侵袭、迁移和转移。(C)2018作者（S）由S发布。Karger AG，巴塞尔
Background/Aims: A recent study found that dysregulated microRNA-184 (miR-184) is involved in the proliferation and survival of nasopharyngeal carcinoma (NPC). This study aimed to evaluate the detailed mechanisms of invasion, migration and metastasis of NPC cells. Methods: Quantitative reverse-transcription PCR (qRT-PCR) and Western blot were used to confirm the expression levels of miR-184 and Notch2. NPC cell invasion and migration were subsequently examined using in vitro cell invasion and wound-healing assays, respectively. MicroRNA (miRNA) target gene prediction databases and dual-luciferase reporter assay were adopted to validate the target genes of miR-184. Results: MiR-184 was downregulated in the NPC cell lines. The miR-184 inhibitor increased the number of invading NPC cells, whereas miR-184 mimics inhibited the invasive ability of such cells. The protein level of E-cadherin decreased, whereas those of N-cadherin and vimentin increased in the anti-miR-184 group. This result showed that miR-184 inhibited NPC cell invasion and metastasis by regulating EMT progression. MiRNA target gene prediction databases indicated the potential of Notch2 as a direct target gene of miR-184. Such a notion was then validated by results of dual-luciferase reporter assay. Notably, shRNANotch2 restrained the EMT and partially abrogated the inhibitory effects of miR-184 on EMT progression in NPC cells. Conclusion: MiR-184 functions as a tumour-suppressive miRNA targeting Notch2 and inhibits the invasion, migration and metastasis of NPC. (C) 2018 The Author(s) Published by S. Karger AG, Basel