Department of Biology, Faculty of Science, Hong Kong Baptist University, Hong Kong, China.
Center for Nasopharyngeal Carcinoma Research, University of Hong Kong, Hong Kong, China.
Sci Rep. 2017 Sep 20;7(1):12012. doi: 10.1038/s41598-017-10695-2.
MicroRNAs (miRNAs) are small non-coding RNAs that play a crucial role in pathogenesis of human cancers. Several miRNAs have been shown to involve in nasopharyngeal carcinoma (NPC) pathogenesis through alteration of gene networks. A global view of the miRNA expression profile of clinical specimens would be the best way to screen out the possible miRNA candidates that may be involved in disease pathogenesis. In this study, we investigated the expression profiles of miRNA in formalin-fixed paraffin-embedded tissues from patients with undifferentiated NPC versus non-NPC controls using a miRNA real-time PCR platform, which covered a total of 95 cancer-related miRNAs. Hierarchical cluster analysis revealed that NPC and non-NPC controls were clearly segregated. Promisingly, 10 miRNA candidates were differentially expressed. Among them, 9 miRNAs were significantly up-regulated of which miR-205 and miR-196a showed the most up-regulated in NPC with the highest incidence percentage of 94.1% and 88.2%, respectively, while the unique down-regulated miR-150 was further validated in patient sera. Finally, the in vitro gain-of-function and loss-of-function assays revealed that miR-150 can modulate the epithelial-mesenchymal-transition property in NPC/HK-1 cells and led to the cell motility and invasion. miR-150 may be a potential biomarker for NPC and plays a critical role in NPC tumourigenesis.
微小 RNA(miRNA)是在人类癌症发病机制中起关键作用的小非编码 RNA。已经有研究表明,通过改变基因网络,一些 miRNA 参与了鼻咽癌(NPC)的发病机制。对临床标本的 miRNA 表达谱进行全面的分析是筛选可能参与疾病发病机制的 miRNA 候选物的最佳方法。在这项研究中,我们使用 miRNA 实时 PCR 平台检测了来自未分化 NPC 患者和非 NPC 对照患者的福尔马林固定石蜡包埋组织中的 miRNA 表达谱,该平台总共涵盖了 95 种与癌症相关的 miRNA。层次聚类分析显示 NPC 和非 NPC 对照组织之间有明显的分离。有希望的是,有 10 个 miRNA 候选物存在差异表达。其中,有 9 个 miRNA 明显上调,其中 miR-205 和 miR-196a 在 NPC 中的上调最为显著,发生率分别为 94.1%和 88.2%,而唯一下调的 miR-150 在患者血清中得到了进一步验证。最后,体外功能获得和功能丧失实验表明,miR-150 可以调节 NPC/HK-1 细胞中的上皮-间充质转化特性,并导致细胞的迁移和侵袭。miR-150 可能是 NPC 的一个潜在生物标志物,在 NPC 的肿瘤发生中起关键作用。
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