长链非编码RNA MIR210HG与miR-210协同调控胃癌转移的作用及其机制

非编码RNA参与多种生理和病理过程，我们已发表工作表明微小RNA在肝癌发生发展中发挥重要作用（Lancet Oncol, 2015; NAR, 2014)。目前通过临床标本检测，我们发现miR-210与其宿主基因MIR210HG均在胃癌中表达上调；进一步实验及软件预测表明两者可能通过抑制SMAD4和STAT6协同促进胃癌细胞迁移侵袭；生物信息学分析提示Sp1，c-Myc结合两者的公用启动子；此外，低氧诱导两者表达。据此，我们提出关键科学问题：1.miR-210与MIR210HG是否通过调控SMAD4和STAT6协同促进胃癌转移。2.Sp1，c-Myc及HIF-1α是否调控miR-210与MIR210HG转录，进而促进其表达。该项目拟探究miR-210与MIR210HG协同促进胃癌转移的作用机制，研究结果将揭示非编码RNA调控胃癌转移新机制，为胃癌治疗提供新靶点。

It is well known that non-coding RNA is involved in a variety of physiological and pathological processes. Our previous work showed that microRNA play a key role in the development of hepatocellular carcinoma (Lancet Oncol, 2015; NAR, 2014). Now we find that both of miR-210 and its host gene MIR210HG upregulate in gastric cancer. Furthermore, miR-210 and MIR210HG may synergistically promote the migration and invasion of gastric cancer cell by inhibiting SMAD4 and STAT6. Bioinformatics analysis indicates that Sp1 and c-Myc may bind to the putative promoter of miR-210 and MIR210HG. Additionally, hypoxia can induce miR-210 and MIR210HG. Thus, we put forward the key scientific problems: 1. Whether miR-210 and MIR210HG synergistically promote the metastasis of gastric cancer by modulating SMAD4 and STAT6? 2. Do Sp1, c-Myc and HIF-1α transcriptionally regulate miR-210 and MIR210HG? In this study, we will disclose the synergistic mechanism of miR-210 and MIR210HG in the metastasis of gastric cancer. In summary, the results of this study will reveal the new mechanism of non-coding RNA in the regulation of gastric cancer metastasis. Particularly, it may provide new targets for the treatment of gastric cancer.