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。Mi R-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。
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-378 overexpression and cell proliferation has been well established. However, no report focused on the cell adhesion change post miR-378 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 miR-378a-5p increasing using immunoblot. Finally, we validated that ZEB1, 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 repressing ZEB1 expression which finally inhibits Wnt signaling pathway and downstream genes.Together, our study provided a novel understanding of miR-378a-5p tumor suppressive function.