Regulation of miR-155 affects the invasion and migration of gastric carcinoma cells by modulating the STAT3 signaling pathway.

Abstract

Studies investigating the effects of microRNA (miR)-155 on the behavior of tumor cells have concentrated primarily on proliferation and apoptosis. The aim of the present study was to investigate the effect of miR-155 inhibitor on the metastatic and invasive ability of gastric carcinoma cells and whether this effect is mediated via the signal transduction and activators of transcription 3 (STAT3) signaling pathway. The miR-155 inhibitor and miR-155 negative control (NC) were transfected into the AGs and MKN-45 cell lines. The migratory and invasive abilities of the cells were analyzed. The level of phosphorylated (p-)STAT3 and the expression levels of matrix metalloproteinases (MMPs), vascular endothelial growth factor (VEGF) and suppressor of cytokine signaling 1 (SOCS1) were also detected. For the AGS cell line, the cell counts (mean ± standard deviation) for the Transwell migration assay were 98.99±9.13 in the miR-155 NC group and 45.32±4.32 in the miR-155 inhibitor group (P<0.01). For the MKN-45 cell line, the cell counts for the migration assay were 129.99±10.12 and 50.36±5.2 in the miR-155 NC and miR-155 inhibitor groups, respectively (P<0.01). The cell counts of the AGS cell line for the invasion assay were 70.25±7.94 in the miR-155 NC group and 40.68±4.73 in the miR-155 inhibitor group (P<0.05). For the MKN-45 cell line, the cell counts for the invasion assay were 84.63±8.12 and 40.35±4.29 in the miR-155 NC and miR-155 inhibitor groups, respectively (P<0.05). Transfection with the miR-155 inhibitor was able to significantly decrease the level of p-STAT3 in the AGS and MKN-45 cell lines compared with the negative control group (all P<0.05). The levels of MMP2 and MMP9 expression were decreased following transfection with miR-155 in AGS and MKN-45 cells (both P<0.05). Notably, transfection with the miR-155 inhibitor was able to decrease the level of VEGF expression, whilst increasing the SOCS1 expression level compared with the negative control group (both P<0.05). Additionally, the downregulation of miR-155 expression in gastric carcinoma cell lines was able to significantly decrease the expression of VEGF, MMP2 and MMP9, thereby inhibiting the invasion and metastasis of gastric carcinoma cells.