MicroRNA-25 promotes gastric cancer migration, invasion and proliferation by directly targeting transducer of ERBB2, 1, and predicts poor patient survival (TUM2P.882)

Abstract

Abstract Gastric cancer (GC) is the most common tumors and the molecular mechanism underlying tumor metastasis is still largely unclear. Here, we show that miR-25 was overexpressed in plasma and primary tumor tissues of GC patients with TNM stage (III or IV) or lymph node metastasis. MiR-25 inhibition significantly decreased the metastasis, invasion and proliferation potential of GC cells in vitro, and reduced their capacity to develop distal pulmonary metastases and peritoneal dissemination in vivo. Furthermore, miR-25 repressed transducer of ERBB2, 1 (TOB1) expression by directly binding to the 3’-UTR, and the inverse correlation was observed between the expressions of miR-25 and TOB1 mRNA in primary GC tissues. Moreover, the loss of TOB1 increased the metastasis, invasion and proliferation of GC cells, and the restoration of TOB1 led to the metastasis, invasion and proliferation suppression. The receiver operating characteristics (ROC) analysis yielded an area under the curve (AUC) value of 0.7325 in distinguishing the GC patients with death from those with living. The analysis of optimal cutoff value revealed significant difference of patients’ survival between GC patients with high plasma concentrations of miR-25 (> 0.2333 amol/μL) and those with low (< 0.2333 amol/μL). Taken together, miR-25 promotes GC progress by directly down-regulating TOB1 expression, and the high concentrations of miR-25 in plasma of GC patients predict poor patient survival.