Hypoxia-induced miR-214 expression promotes tumour cell proliferation and migration by enhancing the Warburg effect in gastric carcinoma cells
Hypoxia-induced miR-214 expression promotes tumour cell proliferation and migration by enhancing the Warburg effect in gastric carcinoma cells
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缺氧诱导miR-214表达通过增强胃癌细胞的Warburg效应促进肿瘤细胞增殖和迁移
DOI：
10.1016/j.canlet.2017.11.007
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发表时间：
2018-02-01
期刊：
影响因子：
9.7
通讯作者：
Zou, Xiaoping
中科院分区：
文献类型：
--
作者：
Yang, Liuqing;Zhang, Weijie;Zou, Xiaoping
miR-214是一种重要的肿瘤iRNA，在包括胃癌在内的各种类型的癌症中上调。然而，miR-214在胃癌中的异位表达和功能的分子机制在很大程度上是不确定的。在本研究中，我们发现miR-214诱导了瓦尔堡效应，促进了人胃癌细胞的迁移和增殖。根据机制分析，miR-214的表达是由环境缺氧诱导的，并且miR-214介导缺氧诱导的功能。然后，我们探索了miR-214增强胃癌细胞中的瓦尔堡效应的分子机制，并鉴定了腺苷A2 A受体（A2 AR）和PR/SET结构域16（PRDM 16）基因为miR-214的直接靶点。综上所述，miR-214抑制胃癌细胞A2 AR和PRDM 16的表达，增强胃癌细胞的瓦尔堡效应，从而促进胃癌细胞的增殖和迁移。这项研究强调了低氧-miR-214-PRDM 16/A2 AR通路在胃癌肿瘤发生中的重要作用，并可能促进针对低氧肿瘤的新疗法的开发。(c)2017爱思唯尔B. V.保留所有权利。
miR-214 is an important oncomiRNA and is upregulated in various types of cancer, including gastric cancer. However, the molecular mechanism underlying the ectopic expression and function of miR-214 in gastric cancer is largely undefined. In this study, we found that miR-214 induces the Warburg effect and promotes the migration and proliferation of human gastric cancer cells. According to the mechanistic analysis, miR-214 expression is induced by environmental hypoxia, and miR-214 mediates hypoxiainduced functions. We then explored the molecular mechanism by which miR-214 enhances the Warburg effect in gastric cancer cells and identified the adenosine A2A receptor (A2AR) and PR/SET domain 16 (PRDM16) genes as the direct targets of miR-214. In conclusion, miR-214 inhibits A2AR and PRDM16 expression and enhances the Warburg effect in gastric cancer cells, thus promoting the proliferation and migration of gastric cancer cells. This study highlights an important role for the hypoxia-miR-214-PRDM16/A2AR pathway in the tumourigenesis of gastric cancer and may facilitate the development of new therapeutics against hypoxic tumours. (c) 2017 Elsevier B.V. All rights reserved.