Galectin-8 Promotes Gastric Cancer Cell Proliferation by Activating the Ras Signaling Pathway

Abstract

Background: Gastric cancer (GC) is one of the most common malignant tumors worldwide, but due to its complex pathogenesis, current treatments are still very limited. Studies have shown that galectin-8 expression is significantly increased in GC and is associated with poor prognosis in patients, but the mechanism of galectin-8 in GC remains unclear. Therefore, this study aimed to investigate the expression, prognostic value, and molecular mechanism of galectin-8 in GC. Methods: UALCAN was used to analyze galectin-8 expression levels in GC and their correlation with clinical stage, histological subtype, and lymph node metastasis. Western blotting and immunohistochemical staining were used to detect the expression levels of galectin-8 in GC tissues. siRNA was transfected using lentivirus to knock down galectin-8. Galectin-8 expression levels and transfection efficacy in GC cells were detected using Western blot. The Cell Counting Kit-8 (CCK-8) assay and colony formation assay were used to detect the level of cell proliferation. Western blotting was used to detect the rat sarcoma viral oncogene homolog (Ras) signaling pathway-related protein expression levels. Immunofluorescence staining was performed for co-localization analysis of galectin-8 and Kirsten Ras (K-Ras) proteins. Results: The expression levels of galectin-8 were significantly increased in GC tissues and cells, and that was positively correlated with clinical stage, histological subtype and lymph node metastasis, and negatively correlated with overall survival. Knockdown of galectin-8 significantly inhibited Human Gastric Adenocarcinoma (AGS) cell proliferation and decreased RAF proto-oncogene serine/threonine-protein kinase (Raf), mitogen-activated protein kinase (Mek), and K-Ras protein expression levels. Immunofluorescence staining results indicated that galectin-8 and K-Ras protein co-localized in the cytoplasm. Conclusions: Galectin-8 promotes GC proliferation by activating the Ras signaling pathway and is a potential therapeutic target and prognostic biomarker for GC.