Department of Gastroenterology, Drum Tower Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210008, China; Department of Infectious Diseases, The First People's Hospital of Lianyungang City, Lianyungang, Jiangsu, China.
Department of General Surgery, Drum Tower Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210008, China; Department of General Surgery, Drum Tower Clinical College of Nanjing Medical University, Nanjing, Jiangsu 210018, China.
Cancer Lett. 2018 Feb 1;414:44-56. doi: 10.1016/j.canlet.2017.11.007. Epub 2017 Nov 10.
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 hypoxia-induced 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.
miR-214 是一种重要的致癌 miRNA，在包括胃癌在内的多种癌症中上调。然而，miR-214 在胃癌中异位表达和功能的分子机制在很大程度上尚不清楚。在本研究中，我们发现 miR-214 诱导了瓦博格效应，并促进了人胃癌细胞的迁移和增殖。根据机制分析，miR-214 的表达受环境缺氧诱导，miR-214 介导了缺氧诱导的功能。然后，我们探索了 miR-214 增强胃癌细胞瓦博格效应的分子机制，并确定了腺苷 A2A 受体（A2AR）和 PR/SET 结构域 16（PRDM16）基因为 miR-214 的直接靶基因。总之，miR-214 抑制 A2AR 和 PRDM16 的表达，增强胃癌细胞的瓦博格效应，从而促进胃癌细胞的增殖和迁移。本研究强调了缺氧-miR-214-PRDM16/A2AR 通路在胃癌发生中的重要作用，并可能有助于开发针对缺氧肿瘤的新疗法。
