In this study, we examined the roles of neurotrophic tyrosine kinase receptor type 2 (NTRK2) gene in regulating in vitro proliferation and invasion in human gastric cancer. Gene expression of NTRK2 was compared between non-carcinoma gastric epithelial cells and gastric cancer (GC) cells by quantitative RT-PCR (qRT-PCR). NTRK2 was either downregulated or upregulated in MKN-28 and SNU-719 cells. The effect of NTRK2 downregulation or upregulation on GC in vitro development was analyzed by qRT-PCR, western blot, proliferation assay, and invasion assay, respectively. The upstream regulator of NTRK2, microRNA-22 (miR-22), was evaluated by dual-luciferase assay. MiR-22 was then upregulated in MKN-28 and SNU-719 cells to examine its regulation on NTRK2 and its encoded protein, tyrosine kinase receptor B (TrkB). In miR-22-upregulated MKN-28 and SNU-719 cells, NTRK2 was further overexpressed to evaluate functional interaction between miR-22 and NTRK2 in GC. NTRK2 was aberrantly upregulated in GC cell lines than in normal gastric cells. In MKN-28 and SNU-719 cells, NTRK2 downregulation inhibited whereas NTRK2 upregulation promoted GC proliferation and invasion in vitro. MiR-22 was verified to be an inverse upstream regulator of NTRK2. In miR-22-upregulated MKN-28 and SNU-719 cells, NTRK2 overexpression partially reversed the miR-22-induced inhibition on cancer proliferation and invasion. NTRK2 is an oncogene and reversely associated with miR-22 in regulating in vitro cancer development in GC.
Keywords: Gastric cancer; Migration; NTRK2; Proliferation; TrkB; miR-22.