Ji Juanjuan, Peng Yi, Niu Tao, Lin Yunhong, Lin Yan, Li Xudong, Wu Xiaoguang, Huang Zhiyong, Zhong Ling, Zhang Shinan
The Second People's Hospital of Yunnan Province Kunming, China.
The Affiliated Stomatology Hospital of Kunming Medical University Kunming 650500, Yunnan Province, China.
Int J Clin Exp Pathol. 2018 Mar 1;11(3):1167-1174. eCollection 2018.
Nasopharyngeal carcinoma (NPC) is a common disease in Southern China with high prevalence. miR-944 has been reported to play a vital role in progression of a variety of cancers. The present study aimed to investigate the potential role of miR-944 in NPC cell migration and invasion through elucidating the interaction with its target genes, MACC1. Expression of miR-944 in NPC tissues and cell lines was examined with quantitative RT-PCR. Overexpressed miR-944 and suppressed miR-944 were established with miR-944 mimics and miR-944 inhibitor, respectively. The effect of miR-944 on cell migration and invasion was determined using Transwell cell migration and Matrigel invasion assay. Luciferase assay was used to determine the target of miR-944. Knocked down of MACC1 was done by MACC1 siRNA. Expression of MET related-markers was examined using Western blot analysis. The expression level of miR-944 was downregulated in NPC tissues and cell lines. Overexpression of miR-944 significantly inhibited the cell migration and invasion in NPC 6-10B cells. In contrast, suppression of miR-944 promoted cell migration and invasion in NPC C-6661 cells. MACC1 is a direct target of miR-944. MACC1 expression was repressed in miR-944 mimic transfected cells while it was enhanced in miR-944 inhibitor transfected cells. MACC1 knock down inhibited cell migration and invasion. Either miR-944 restoration or MACC1 knockdown caused enhanced E-cadherin, reduced N-cadherin, and vimentin expression. In conclusion, miR-944 could inhibit MET and metastasis of NPC by targeting MACC1. This study suggests that miR-944 has anti-tumor and anti- metastatic properties and could thus be a novel therapeutic agent for NPC treatment.
鼻咽癌（NPC）是中国南方一种常见且高发的疾病。据报道，miR-944在多种癌症的进展中起着至关重要的作用。本研究旨在通过阐明miR-944与其靶基因MACC1的相互作用，探讨miR-944在NPC细胞迁移和侵袭中的潜在作用。采用定量RT-PCR检测NPC组织和细胞系中miR-944的表达。分别用miR-944模拟物和miR-944抑制剂建立miR-944过表达和抑制表达体系。使用Transwell细胞迁移和基质胶侵袭实验来确定miR-944对细胞迁移和侵袭的影响。采用荧光素酶报告基因实验确定miR-944的靶标。通过MACC1 siRNA敲低MACC1。使用蛋白质免疫印迹分析检测MET相关标志物的表达。miR-944在NPC组织和细胞系中的表达水平下调。miR-944过表达显著抑制NPC 6-10B细胞的迁移和侵袭。相反，抑制miR-944可促进NPC C-6661细胞的迁移和侵袭。MACC1是miR-944的直接靶标。在转染miR-944模拟物的细胞中MACC1表达受到抑制，而在转染miR-944抑制剂的细胞中MACC1表达增强。敲低MACC1可抑制细胞迁移和侵袭。miR-944恢复表达或MACC1敲低均导致E-钙黏蛋白表达增加、N-钙黏蛋白和波形蛋白表达减少。总之，miR-944可通过靶向MACC1抑制NPC的上皮-间质转化和转移。本研究表明，miR-944具有抗肿瘤和抗转移特性，因此可能成为治疗NPC的新型治疗药物。
