TRIM14 promotes the migration and invasion of gastric cancer by regulating epithelial-to-mesenchymal transition via activation of AKT signaling regulated by miR-195-5p

Tripartite motif-containing 14 (TRIM14) is a member of the TRIM protein family which has been implicated in several critical processes and is dysregulated in human cancers in a cancer-specific trend. However, its expression and function in human gastric cancer (GC) are still largely unknown. In this study, we confirmed for the first time that TRIM14 mRNA and protein were upregulated in GC tissues and cell lines as determined by qRT-PCR and western blot analysis. Clinical data disclosed that high TRIM14 expression was significantly associated with aggressive prognostic features, including advanced TNM stage and lymph node metastasis. In regards to 5-year survival, TRIM14 served as a potential prognostic marker for GC. Notably, TRIM14 promoted migration, invasion as measured by Transwell and epithelial-to-mesenchymal transition (EMT) as determined by western blot analysis and immunofluorescence (IF) in vitro and in vivo. Moreover, TRIM14 induced protein kinase B (AKT) pathway activation, and inhibition of AKT reversed the TRIM14-induced promotive effects on cell migration, invasion and EMT progression. Furthermore, we demonstrated that TRIM14 expression was regulated by miR-195-5p. miR-195-5p exerted an inhibitory role in GC migration and invasion. Finally, we confirmed that alteration of TRIM14 expression abolished the effects of miR-195-5p on GC cells. Conclusively, our results demonstrated that TRIM14 functions as an oncogene in regulating EMT and metastasis of GC via activating AKT signaling, which was regulated by miR-195-5p, supporting its potential utility as a therapeutic target for GC.