吕青 苏红 王纠 黄努努 张雅鸥.MiR-378a-5p直接靶ZEB1向上调鼻咽癌CNE-1细胞E-cadherin表达*[J].,2016,16(2):201-205 |
MiR-378a-5p直接靶ZEB1向上调鼻咽癌CNE-1细胞E-cadherin表达* |
MiR-378a-5p Up-regulates E-cadhern Expression by Targeting ZEB1 inNasopharyngeal Caecinoma CNE-1 cells |
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DOI: |
中文关键词: miR-378a-5p 钙粘附蛋白E;EZB1 ;鼻咽癌 |
英文关键词: MiR-378a-5p E-cadherin ZEB1 Nasopharyngealcarcinoma |
基金项目:国家自然科学基金项目(31371315) |
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中文摘要: |
目的: Mir-378a-5p是一种被发现多年的微小RNA,其在包括肺癌、结肠癌和乳腺癌等多种肿瘤中都被认为具有抑制肿瘤生
长的作用。Mir-378a-5p与细胞增殖的关系在多篇文章中已经有较为详细的阐述,然而,目前没有报道提及miR-378a-5p是否通过
作用于细胞迁移和细胞粘附途径从而达到抑制肿瘤生长的作用。方法与结果:在本研究中,我们通过wound healing 和trans-well
的方法发现在鼻咽癌细胞CNE-1 中过表达miR-378a-5p显著的抑制了细胞迁移以及细胞浸润的过程。通过免疫印迹方法,我们
揭示了细胞粘附因子E-cadherin在过表达miR-378a-5p后显著上调。通过生物信息学的方法,我们预测了miR-378a-5p的可能作
用靶点,并通过双荧光报告载体的方法证实了ZEB1是miR-378a-5p的直接靶点。结论:我们的研究提示了miR-378a-5p造成的E-cadherin
的上调是通过直接抑制E-cadherin的负调控因子ZEB1造成的。E-cadherin的上调不但影响了细胞的迁移和粘附,而且
通过间接阻断Wnt通路抑制了下游控制细胞增殖的基因表达。本研究为理解miR-378a-5p的肿瘤抑制作用提供了一个新的作用
机理。 |
英文摘要: |
Objective:MiR-378a-5p was identified for decades and its tumor repressive role was demonstrated in various types of
cancer including lung cancer, colorectal cancer and breast cancer etc. The relationship between miR-378a-5p overexpression and cell
proliferation has been well established. However, no report focused on the cell adhesion change miR-378a-5p post induction.Methods and Results:In this article, we discovered treated cells with miR-378a-5p greatly represses cell migration and invasion in nasopharyngeal
carcinoma CNE-1 cells by using wound healing assay and trans-well assay, respectively. We also revealed that E-cadherin expression
was significantly elevated upon increasing using immunoblot. Finally, we validated that , an important negative
regulator of E-cadherin, was a direct target of miR-378a-5p by dual luciferase assay.Conclusion:Our result suggests that miR-378a-5p
up-regulates E-cadherin expression by repressingZEB1 expression which finally inhibits Wnt signaling pathway and downstream genes.
Together, our study provided a novel understanding of miR-378a-5p tumor suppressive function. |
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