恶性肿瘤转移的调控机制尚未完全阐明。我们在国际上率先发现：miR-19a/b的高表达与胃癌转移正相关；miR-19a/b能促进胃癌细胞的体内外转移；MXD1是miR-19a/b的靶基因；MXD1的高表达能抑制c-Myc和miR-19a/b的表达并阻遏胃癌恶性表型的发生。文献回顾提示：c-Myc能直接转录激活miR-19a/b；MXD1能直接或间接拮抗c-Myc的功能；上述分子均与肿瘤转移相关。我们推测，c-Myc-miR-19a/b-MXD1组成的环路可能参与了胃癌的转移。本项目拟先明确上述分子在胃癌转移细胞和组织中的表达规律，再利用基因转染分别调变它们的表达，通过体内外转移实验阐明它们对胃癌转移的调控，并借助报告基因实验、免疫共沉淀、western blot、PCR等明确上述正反馈环路的存在及其对胃癌转移的调控机制，为明确miRNA对胃癌转移的调控作用及机制提供理论依据。

It has not been elucidated why malignant cancer cells are prior to metastasize. From what we have studied prior to others, the highly expression of miR-19a/b had positive correlation with the metastasis of gastric cancer. From functional assays, we found that miR-19a/b promoted the in vitro and in vivo metastatic ability of gastric cancer cells. Furthermore, report gene assay and functional assays revealed that MXD1 is a direct target of miR-19a/b. Moreover, the highly expression of MXD1 suppressed the expression of c-Myc and miR-19a/b and inhibited the malignant phenotypes of gastric cancer cells. From what has been reported, the proto-oncogene c-Myc directly trans-activates the expression of miR-19a/b and MXD1 could directly or indirectly antagonize the function of c-Myc. Furthermore, the above molecules were reported to be associated with cancer metastasis. Therefore, we rank the first in the world to speculate that the feedback loop constituted by c-Myc, miR-19a/b and MXD1 might be involved in the process of gastric cancer metastasize. In future studies, we will first explore the expression pattern of miR-19a/b, MXD1 and c-Myc in metastasized gastric cancer tissues and cells. Secondly, using gene transfection assay and functional assays, we will change the expression levels of the above molecules and explore their regulatory ability in the metastasis of gastric cancer cells. Furthermore, report gene assay, CoIP, western blot and real-time PCR will be used to explore the existence of the potential positive feedback loop (c-Myc－miR-19a/b－MXD1) and the mechanisms in regulating the metastasis of gastric cancer. The present study would provide theoretical evidence and would be helpful for the understanding of cancer metastasis, the finding of new cancer metastatic markers, and the designation of new anti-metastatic therapeutic strategies.