Abstract
56 Background: Migration and invasion of cancer cells are essential process during cancer metastatic procession. In gastric cancer, cells invasion into the surrounding tissue is a crucial early step. However, the mechanisms have not been fully understood. MicroRNAs, which are a class of small single-stranded non-coding RNA, participate in the malignant progressions of cancer, including metastasis. We study the association between specific dysregulated miRNA and specific metastasis step of gastric cancer, which will provide insights into the potential mechanisms of gastric cancer cells migration, invasion and metastasis. Methods: The expression of miR-375 was assayed using the quantitative real-time PCR analysis. Scratch-wound healing assay, Transwell migration and invasion assay were conducted to study the migration and invasion abilities of cells. Animal experiment was also conducted to examine the effect on liver and lung metastases by overexpression of miR-375. Luciferase assay was conducted to study the association between Snail and miR-375. Results: MiR-375 is downregulated in gastric cancer cells with greater migration and invasion abilities. The expression level of miR-375 is decreased in gastric cancer tissues from metastasis-positive patients compared with that from metastasis-free patients. Overexpression of miR-375 inhibits the migration and invasion abilities of gastric cancer cells. JAK2, which may be a target gene of miR-375, could reverses miR-375 induced inhibition of gastric cancer cells migration and invasion. Liver metastasis was not detected in mice injected with miR-375 overexpressed cells but was apparent in mice injected with cells which were transfected with control vector. The transcription factor Snail, which binds directly to the putative promoter of miR-375, could reduce the expression level of miR-375 significantly. A distinct inverse correlation was found between miR-375 expression and Snail mRNA level. Conclusions: These findings demonstrate that tumor suppressor miR-375, whose expression is directly regulated by the transcription factor Snail, inhibits gastric cancer cells migration, invasion and metastasis by targeting an important protein JAK2.
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