However, the regulatory mechanisms remain unclear. In the present study, we further explored the function and potential mechanisms of miR-375 in the migration and invasion of Benzethonium Chloride gastric cancer cells. We found that overexpression of miR-375 inhibited proliferation, migration, and invasion of gastric cancer cells partially by targeting JAK2. It has been over a decade since JAK2 was first cloned. JAK2 is expressed in nearly every tissue and associated with many pathologic progresses. Although it is evident that JAK2 acts as an oncogene in both myeloproliferative disorders and some solid tumors, no direct involvement of JAK2 in cancer migration, invasion or metastasis has been reported. Excitingly, our study first demonstrated that knocking down JAK2 by RNAi inhibited the migration and invasion activities of gastric cancer cells similar to that of the overexpression of miR-375. Besides, overexpression of JAK2 could promote the migration and invasion of gastric cancer cells. Thus, we assumed that JAK2 might counteract the inhibitory effect on the cells migration and invasion caused by miR-375. Given the critical role of miR-375 and JAK2 as master regulators in gastric cancer cells proliferation, migration, and invasion, both of them has Oxysophocarpine therapeutic potential in gastric cancer treatment. Therefore, it remains to be investigated whether there is other targets participate in miR-375 mediated gastric metastasis. Of particular interest, we further studied how miR-375 involved in the gastric carcinogenesis. Although there is an evident that DNA methylation and histone deacetylation are the possible mechanisms involved in the downregulation of miR-375 in gastric cancer. The mechanisms underlying miR-375 dysregulation in gastric cancer metastasis are still poorly understood. There is possibility for a transcriptional blockage of miR-375 gene expression in this process. Here we show that the metastasis associated transcription factor Snail is a potential upstream regulator of miR-375 expression. Snail is a DNA-binding zinc finger protein and has been reported as transcriptional repressor. Acumulating evidences show that Snail binds to E-boxes in the promoter of E-cadherin and represses its transcription to regulate tumor invasion development. Moreover, overexpression of Snail in cancers was found to be associated with lymph node metastasis, tumor relapse and prognosis. In consistent with other reports, our study found that Snail mRNA is overexpressed in gastric cancer tissues when compared with their adjacent non-malignant tissues. As the promoter activity of miR-375 could be suppressed by Snail and overexpression of Snail could reduce miR-375 expression level significantly, we further found a distinct inverse correlation between the expression level of miR-375 and the level of Snail mRNA in gastric cancer samples. Snail is also found to be involved in the regulation of gastric cancer cells migration by targeting miR-375. In conclusion, we have identified that miR-375 was aberrantly expressed in the gastric cancer tissues from metastasis-positive patients or gastric cancer cells with greater migration and invasion activities when compared with tissues from metastasis-free patients or non-invasive gastric epithelial cell line GES-1 respectively. Overexpression of miR-375 reduced gastric cancer cells migration and invasion activities at least partially by targeting JAK2. Moreover, Snail may be an upstream regulator of miR-375 which negatively regulates the expression of miR-375.