ObjectiveTMEM119 is a member of transmembrane proteins family, which is abnormally expressed in human cancers and associated with tumorigenesis. In this study, we focused on the expression of TMEM119 and its role in cell invasion and migration in gastric cancer.MethodsReal-time polymerase chain reaction, Western blotting, and immunohistochemistry were performed to examine the expression of TMEM119 in gastric cancer tissues and cell lines. After transfection with TMEM119 siRNA or recombined TMEM119-expressing vector, the invasion and migration ability of MKN45 and SGC-7901 cells was measured by transwell assay. The expression of TMEM119, p-STAT3, STAT3, VEGF, MMP2, and MMP9 proteins in SGC-7901 and MKN45 cells treated with TMEM119 siRNA, TMEM119-expressing vector, or AG490 was measured by Western blotting.ResultsWe found that higher TMEM119 expression was found in gastric cancer tissues and cell lines and was associated with lower survival rate. TMEM119 knockdown inhibited SGC-7901 cell invasion and migration, along with the expression of p-STAT3, VEGF, MMP2, and MMP9. TMEM119 overexpression promoted MKN45 cell invasion and migration, along with the expression of p-STAT3, VEGF, MMP2, and MMP9. Additionally, AG490 treatment significantly corrected TMEM119-induced MKN45 cell migration and invasion and expression of p-STAT3, VEGF, MMP9, and MMP2 proteins.ConclusionThe results indicated that TMEM119 promotes gastric cancer cell migration and invasion through activation of STAT3 signaling pathway, and TMEM119 may therefore act as a novel therapeutic target for gastric cancer.

Gastric cancer is the second major cause of death associated with cancer and ranks among the top four cancers diagnosed worldwide. Previous findings identified the association of transmembrane proteins (TMEMs) with tumorigenesis of various types of cancer, including breast, liver and kidney cancer. However, the expression and the biological function of TMEMs, especially TMEM119, and its possible molecular mechanism in gastric cancer remain less understood. CCK-8 and flow cytometric analysis was employed to examine the viability and apoptosis of gastric adenocarcinoma SGC-7901 and AGS cells, gastric carcinoma MKN45 cells, as well as gastric epithelial cell lines GES-1 after transfection with TMEM119-siRNA (siTMEM119), respectively. Quantitative PCR, western blot analysis and immunohistochemistry was performed to detect the expression levels of TMEM119, Bax, Bcl-2 and caspase-3. The results showed that, TMEM119 was elevated with the highest expression detected in SGC-7901 cells compared to AGS cells, MKN45 cells, as well as GES-1. TMEM119 silencing in the gastric cancer cell line, SGC-7901, significantly inhibited cell viability and induced apoptosis. The downregulation of TMEM119 exhibited reduced levels of Bcl-2 and higher levels of Bax and caspase-3 in SGC-7901 cells. These results suggest that TMEM119 is useful in the treatment of gastric cancer.