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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。
Purpose: MiR-378a-5p is a multi-year discovered microRNA that is thought to inhibit tumor growth in a variety of tumors, including lung, colon and breast cancers. The relationship between miR-378a-5p and cell proliferation has been described in more detail in several articles. However, it has not been reported to date whether miR-378a-5p inhibits tumors by acting on cell migration and cell adhesion pathways The role of growth. Methods and Results In the present study, we found that miR-378a-5p overexpression in nasopharyngeal carcinoma CNE-1 significantly inhibited cell migration and cell infiltration by wound healing and trans-well methods. By immunoblotting, we revealed that the cell adhesion factor E-cadherin is significantly up-regulated upon overexpression of miR-378a-5p. By bioinformatics methods, we predicted the possible targets of miR-378a-5p and confirmed that ZEB1 is a direct target of miR-378a-5p by dual fluorescence reporter. CONCLUSIONS: Our study suggests that the upregulation of E-cadherin by miR-378a-5p is caused by the direct inhibition of the negative regulator of E-cadherin, ZEB1. Upregulation of E-cadherin not only affects cell migration and adhesion but also inhibits downstream gene expression that controls cell proliferation by blocking the Wnt pathway indirectly. This study provides a new mechanism of action for understanding the tumor suppressive effect of miR-378a-5p.