Abstract
Gastric cancer is a malignancy with a high incidence and poor prognosis. The identification of novel molecular markers and elucidation of their underlying mechanisms may provide new avenues for improving therapeutic strategies. The present study analyzed the association between GPR176 expression and clinicopathological features using The Cancer Genome Atlas‑Stomach Adenocarcinoma and GSE66254 datasets, and further validated the findings in patients from The First Affiliated Hospital of Guangxi Medical University (Nanning, China). The migratory and invasive abilities of gastric cancer cells were assessed using Transwell and wound‑healing assays. Western blotting was carried out to evaluate the effects of GPR176 on the PI3K/AKT/mTOR signaling pathway. In vivo tumorigenesis assays in nude mice were carried out to confirm the role of GPR176 in tumor progression. Analysis revealed that GPR176 expression was significantly elevated in gastric cancer tissues and associated with unfavorable patient outcomes. Silencing GPR176 markedly suppressed the migration and invasion of gastric cancer cells, accompanied by inhibition of the PI3K/AKT/mTOR and EMT signaling pathways. These inhibitory effects were prevented by the overexpression of PIP5K1A. In line with the in vitro results, experiments with nude mice demonstrated that GPR176 knockdown impeded tumor growth, whereas its overexpression enhanced tumorigenicity. Furthermore, GPR176 suppression significantly attenuated EMT and PI3K/AKT/mTOR signaling in vivo, while GPR176 overexpression led to activation of these pathways. In summary, the present study identifies GPR176 as a novel prognostic biomarker in gastric cancer. Mechanistically, GPR176 promotes EMT and tumor progression, at least in part, through activation of the PI3K/AKT/mTOR signaling pathway.