TRIP13 Promotes Gastric Cancer Cell Proliferation,Migration And Invasion Through PI3K/AKT/mTOR Signaling Pathway

Aims: To analyze the expression of TRIP13 in gastric cancer(GC)and its clinical significance,and to explore its effects on the proliferation,migration and invasion ability of gastric cancer cells and its mechanism.Methods: Public data downloaded from Gene expression profiling interactive analysis(GEPIA)and Gene expression omnibus(GEO)were selected to explore the expression levels of TRIP13 m RNA in GC samples and normal non-cancerous samples.Western blot,IHC and q RT-PCR were used to investigate the m RNA and protein levels of TRIP13 in GC and paired non-cancerous tissues,and the associations between TRIP13 expression and clinicopathological parameters were then evaluated.Western blot and q RT-PCR to detect the difference in TRIP13 expression in GC cell lines versus normal gastric mucosal cell lines.Transient transfection of TRIP13 small interfering RNA(si RNA)into GC cells to explore the effects of silencing TRIP13 on the proliferation,migration and invasion ability of gastric cancer cells by CCK-8,clone formation,Ed U and Transwell assays.The influences of TRIP13 on GC cell proliferation,migration and invasion were studied in vitro using CCK-8,clone formation,Ed U and transwell assays,and in vivo by subcutaneous xenotransplantation and lung metastasis models.Additionally,western blot was performed to assess the roles of dysregulated TRIP13 on the downstream signaling pathway of TRIP13 and its mechanism of action.Results: Results from GEPIA and GEO dataset analysis revealed that relative m RNA levels of TRIP13 were significantly higher in GC samples compared with the normal samples.Evidenced from western blot,IHC and q RT-PCR detections of collected GC samples,TRIP13 was obviously upregulated in GC samples in relative to the adjacent non-cancerous specimens.Then,TRIP13 was knocked down by si RNA and relative lentivirus in GC cells(MGC803 & BGC823).A series of loss-of function assays,including CCK-8,colony formation,Ed U,Transwell assays and animal models,disclosed that knockdown of TRIP13 could significantly suppress GC cell growth,migration and invasion in vitro and vivo.Further assessments of western blot showed that depletion of TRIP13 significantly inhibited PI3K/AKT/m TOR signaling pathway in GC.Conclusions: TRIP13 is overexpressed in GC.Knockdown of TRIP13 significantly inhibited GC cell growth,migration and invasion via PI3K/AKT/m TOR signaling pathway,highlighting its potential as a potential oncogene in GC.