NLK, a novel target of miR-199a-3p, functions as a tumor suppressor in colorectal cancer
NLK, a novel target of miR-199a-3p, functions as a tumor suppressor in colorectal cancer
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NLK 是 miR-199a-3p 的新靶点，在结直肠癌中发挥肿瘤抑制因子的作用
DOI：
10.1016/j.biopha.2014.05.003
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发表时间：
2014-06-01
影响因子：
7.5
通讯作者：
Zhao, Hong
中科院分区：
文献类型：
--
作者：
Han, Ye;Kuang, Yuting;Zhao, Hong
我们以前报道过miR-199 a-3 p是一种新的诊断结直肠癌的生物标志物和新的预后指标。然而，miR-199 a-3 p的调控机制及其靶基因尚不清楚。本研究通过荧光素酶报告基因检测和蛋白质印迹分析证实miR-199 a-3 p可以直接靶向NLK基因的3 '-UTR。我们检测了92例结直肠癌中NLK的表达，以评估其在结直肠癌中的临床病理特征。结果显示NLK在胃癌组织中的表达明显低于NAT，且NLK低表达与淋巴结转移、静脉浸润、肝转移及TNM分期有关（P < 0.05）。Kaplan-Meier分析显示NLK低表达与结直肠癌患者的总生存率相关（P < 0.05）。在体外实验中，NLK抑制了大肠癌细胞的增殖、克隆形成、伤口愈合、迁移和侵袭等生物学行为（P < 0.05），而过表达NLK则增加了大肠癌细胞的凋亡率。这些结果表明NLK是一个已鉴定的miR-199 a-3 p靶基因，在结直肠癌中具有抑癌基因的功能。NLK可能是开发结直肠癌诊断和治疗方法的新方向。(C)2014年Elsevier Masson SAS。All rights reserved.
We previously reported that miR-199a-3p is a newly biomarker for diagnosis and novel prognostic indicator in colorectal cancer. However, the miR-199a-3p regulatory mechanism and its target genes are still unclear. In our present study, we demonstrated miR-199a-3p could directly target 3'-UTR of NLK gene by luciferase reporter assay and western blot analysis. We detected NLK expressions in 92 colorectal cancer cases to evaluate its clinicopathologic characteristics in colorectal cancer. Our results showed that NLK expression was significantly downregulated in cancer tissues than NATs, and NLK low-expression was associated with lymph node metastasis, venous invasion, liver metastasis and the TNM stage (P < 0.05). Moreover, Kaplan-Meier analysis showed that low expression of NLK correlated with a shorter overall survival rates of patients with CRC (P < 0.05). In vitro, we also found that NLK suppressed the biological behaviors of colorectal cancer cells, including the abilities of cell proliferation, clone formation, wound healing, migration and invasion (P < 0.05), while overexpression of NLK increased the apoptotic rate of colorectal cancer cells. All these results suggested that NLK was an identified miR-199a-3p target gene and functioned as a tumor suppressor gene in colorectal cancer. NLK could be a novel direction for developing diagnostic and therapeutic approaches in colorectal cancer. (C) 2014 Elsevier Masson SAS. All rights reserved.