MicroRNA-124 inhibits cell invasion and epithelial-mesenchymal transition by directly repressing Snail2 in gastric cancer

OBJECTIVE: MicroRNAs (miRNAs) act as critical regulators of genes expression involved in tumor biological processes. The study aimed to investigate the clinical significance and biological role of miR-124 in gastric cancer (GC).

PATIENTS AND METHODS: MiR-124 expression was analyzed from 88 GC tissues and adjacent normal tissues by quantitative Real-time PCR (qRT-PCR). Kaplan-Meier curves and log-rank test was used to evaluate the association between miR-124 and the over survival (OS) time of GC patients. MTT assays and transwell invasion assays were performed to assess cell proliferation and invasion. The relationship between miR-124 and Snail2 expression was analyzed by dual luciferase reporter assay. Western blot analyses were performed to detect the relative protein expression.

RESULTS: We found that miR-124 expression was significantly reduced in GC tissue samples when compared to the adjacent normal tissues (p<0.05). Lower miR-124 was found to be associated with tumor size (p=0.001), lymphatic metastasis (p=0.008) and TNM stage (p=0.015). Furthermore, patients who have lower miR-124 predicted poor OS time (p<0.05). Function studies suggested that cell proliferation and invasion ability of GC cells were inhibited by up-regulation of miR-124 expression. Moreover, we demonstrated that Snail2 was a direct target of miR-124. Meanwhile, miR-124 inhibited Epithelial-Mesenchymal Transition (EMT) process by repressing the Snail2 expression in GC cells.

CONCLUSIONS: MiR-124 acted as a tumor suppressor in GC and may be a useful target for GC treatment.

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