Department of Digestive Medicine, Second Affiliated Hospital of Nanjing Medical University, No. 121 Jiang Jia Yuan Road, Nanjing, China.
Department of Digestive Medicine, Jiangsu Rudong County People's Hospital, Nanjing, China.
Funct Integr Genomics. 2023 Jan 6;23(1):29. doi: 10.1007/s10142-022-00927-8.
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.
本研究旨在探讨 Girdin 在胃癌（GC）中的表达，研究 Girdin 对 GC 细胞表型的影响，并阐明其潜在机制。通过免疫组织化学（IHC）和实时定量 PCR（qRT-PCR）检测 GC 组织中 Girdin 的表达。用 Girdin 靶向 siRNA 转染 GC 细胞，然后分别检测 GC 细胞的增殖、迁移、侵袭和凋亡。此外，通过 Western blot 检测蛋白表达。同时，进行肿瘤植入实验以检测体内 Girdin 敲低的效果。结果表明，GC 组织中 Girdin 表达上调，与不良预后相关。Girdin 敲低抑制 GC 细胞增殖、迁移和侵袭，促进细胞凋亡和细胞周期阻滞。Girdin 促进 AKT、GSK3β 和 β-catenin 的磷酸化。此外，Girdin 抑制 β-catenin 的磷酸化。Girdin 抑制细胞凋亡，刺激细胞迁移和侵袭，而 AKT 抑制剂（MK2206）处理逆转了 Girdin 过表达的作用，GSK3β 抑制剂（CHIR99021）处理增强了 Girdin 过表达对 GC 细胞的作用。此外，Girdin 体内抑制肿瘤生长。总之，Girdin 在 GC 组织中异常表达，通过调节 AKT/GSK3β/β-catenin 信号通路促进 GC 的发展。
