RESUMO
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.
RESUMO
Homeobox A5 (HOXA5) is a member of the homeobox (HOX) family and was upregulated in many types of tumors. However, its expression and role in esophageal squamous cell carcinoma (ESCC) remain unclear. In this study, the aim of this study was to investigate the expression and function of HOXA5 in ESCC. Our results showed that HOXA5 was highly expressed in ESCC cell lines. The in vitro experiments demonstrated that knockdown of HOXA5 significantly inhibited the proliferation, migration and invasion of ESCC cells. Furthermore, the in vivo experiments showed that knockdown of HOXA5 significantly inhibited the tumor growth of ESCC in mice xenograft model. Finally, sh-HOXA5 inhibited the expression of ß-catenin, cyclin D1 and c-Myc in ESCC cells. Taken together, these data revealed that knockdown of HOXA5 suppressed the proliferation and metastasis partly by interfering with Wnt/ß-catenin signaling pathway in ESCC cells. Therefore, these findings suggest that HOXA5 may be a potential therapeutic target for the treatment of ESCC.
