MiR-451 inhibits cell growth and invasion by targeting MIF and is associated with survival in nasopharyngeal carcinoma.
MiR-451 inhibits cell growth and invasion by targeting MIF and is associated with survival in nasopharyngeal carcinoma.
复制标题
MiR-451 通过靶向 MIF 抑制细胞生长和侵袭，并与鼻咽癌的生存相关
DOI：
10.1186/1476-4598-12-123
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发表时间：
2013-10-20
期刊：
影响因子：
37.3
通讯作者：
Ma J
中科院分区：
文献类型：
--
作者：
Liu N;Jiang N;Guo R;Jiang W;He QM;Xu YF;Li YQ;Tang LL;Mao YP;Sun Y;Ma J
背景
miRNAs在包括肿瘤发生在内的多种生物学过程中发挥重要作用。然而，miR-451在鼻咽癌中的作用机制尚不清楚。
方法
采用定量RT-PCR方法检测miR-451在鼻咽癌细胞系和临床组织中的表达。Kaplan-Meier曲线用于估计miR-451表达与生存之间的关联。进行MTT、集落形成、Transwell迁移和侵袭试验以及异种移植模型。使用荧光素酶报告基因测定、定量RT-PCR和蛋白质印迹法确认miR-451靶标。
结果
miR-451在鼻咽癌细胞系和临床组织中表达显著下调（P0.01）. miR-451低表达患者的总生存期（HR，1.98; 95%CI，1.16-3.34; P = 0.01）和无病生存期（HR，1.68; 95%CI，1.07-2.62; P = 0.02）低于高表达患者。多因素考克斯回归分析显示miR-451是影响鼻咽癌预后的独立因素。miR-451的异位表达在体外抑制细胞活力、集落形成、细胞迁移和侵袭，并且在体内抑制异种移植肿瘤生长。MIF被证实是miR-451的直接靶点，并且MIF调节NPC细胞的生长和侵袭。
结论
新发现的miR-451/MIF通路为NPC的发生和进展提供了新的见解，并可能代表一种新的治疗靶点。
Background
MiRNAs play important roles in diverse biological processes including tumorigenesis. However, little is known about the function and mechanism of miR-451 in nasopharyngeal carcinoma (NPC).
Methods
Quantitative RT-PCR was used to quantify miR-451 expression in NPC cell lines and clinical tissues. Kaplan-Meier curves were used to estimate the association between miR-451 expression and survival. The MTT, colony formation, Transwell migration and invasion assays, and a xenograft model were performed. A miR-451 target was confirmed using luciferase reporter assays, quantitative RT-PCR, and Western blotting.
Results
MiR-451 was significantly downregulated in NPC cell lines and clinical tissues (P 0.01). Patients with low expression of miR-451 had poorer overall survival (HR, 1.98; 95% CI, 1.16-3.34; P = 0.01) and disease-free survival (HR, 1.68; 95% CI, 1.07-2.62; P = 0.02) than patients with high expression. MiR-451 was an independent prognostic factor in NPC in multivariate Cox regression analysis. Ectopic expression of miR-451 suppressed cell viability, colony formation, and cell migration and invasion in vitro, and inhibited xenograft tumor growth in vivo. MIF was verified as a direct target of miR-451, and MIF regulated NPC cell growth and invasion.
Conclusions
The newly identified miR-451/MIF pathway provides insight into NPC initiation and progression, and may represent a novel therapeutic target.
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