BackgroundGastric cancer (GC) is a prevalent cancer with high mortality and strong invasiveness, and the entire regulatory networks of GC is still unclear.ObjectiveThe aim of this study was to explore the specific mechanism of the effect of nucleolar protein 6 (NOL6) on the proliferation and apoptosis of GC cells.MethodsThe human gastric adenocarcinoma cell line HGC-27 and AGS were cultured. qRT-PCR was used to verify the expression level of NOL6 in GC cells; MTT and EdU were used to test cell proliferation; TUNEL staining and Flow cytometry were used to detect cell apoptosis; The downstream genes and pathways following NOL6 knockdown were explored through the microarray assay and ingenuity pathway analysis, and the downstream genes were finally verified by qRT-PCR and Western blotting. The xenograft mice were used to investigate the effect of NOL6 on GC in vivo.ResultsTCGA data analysis showed that NOL6 expression level was higher in GC cells than adjacent normal cells. Over-expression of NOL6 increased proliferation and colony formation, and inhibited the apoptotic rate in AGS and HGC-27 cells, while NOL6 knockdown induced the opposite effects. Through microarray assay and IPA analysis, NOL6-related downstream genes and critical signaling pathways were found. And we verified the relationship between downstream genes and GC. Additionally, NOL6 knockdown could decrease the weight and volume of tumor in the mice.ConclusionNOL6 knockdown could inhibit cell proliferation and induce cell apoptosis of GC, suggesting that NOL6 may serve as a potential therapeutic target for treating GC.

ThE present work focused on exploring Girdin expression within gastric cancer (GC), examining the effect of Girdin on the cell phenotype of GC, and clarifying the underlying mechanisms. Girdin expression in GC samples was identified by immunohistochemistry (IHC) and quantitative real-time PCR (qRT-PCR) assays. Girdin-targeting siRNAs were transfected into GC cells; later, we examined GC cell proliferation, migration, invasion, and apoptosis, respectively. Additionally, the protein expression was examined through Western blotting assay. Moreover, the tumor implantation experiment was conducted for examining Girdin knockdown in vivo. The results showed that Girdin expression elevated within GC samples, which was associated with the dismal prognostic outcome. Girdin knockdown suppressed GC cell proliferation, migration, and invasion, and enhanced apoptosis and cell cycle arrest. Girdin promoted the phosphorylation of AKT, GSK3β, and β-catenin. Moreover, Girdin inhibited the phosphorylation of β-catenin. Girdin suppressed cell apoptosis and stimulated cell migration and invasion, while AKT inhibitor (MK2206) treatment reversed the effect of Girdin overexpression, and GSK3β inhibitor (CHIR99021) treatment enhanced the effect of Girdin overexpression on GC cells. Besides, Girdin delayed tumor growth in vivo. In conclusion, Girdin was abnormally expressed in GC samples, which promoted the development of GC by regulating AKT/GSK3β/β-catenin signaling.