Galectin-8 Promotes Gastric Cancer Cell Proliferation By Activating The RAS Signaling Pathway

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.Surgery and chemotherapy are still the main methods for the treatment of gastric cancer,among which neoadjuvant chemotherapy and postoperative chemotherapy have important significance in inhibiting the proliferation of gastric cancer cells to achieve the therapeutic purpose.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.Western blotting and q-PCR was used to analyze galectin-8 expression levels in GC cells.Galectin-8 gene and protein were highly expressed in AGS gastric cancer cell lines.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.Cell proliferation was detected by cell counting Kit-8(CCK-8)and colony formation assay.The expression levels of Ras signaling pathway related proteins of rat sarcoma virus were detected by Western blotting.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.