YB-1 Promotes Pancreatic Cancer Cell Growth Through GSK-3? Expression

Purpose:In a variety of malignant tumors, the overexpressionof YB-1 can promote tumor occurrence and development. While the expression of YB-1 in pancreatic carcinoma, and its relationship with pancreatic cancer, had no clear reports. Therefore, this study aimed to investigate the expression of YB-1 in human pancreatic carcinoma and its role of pancreatic cancer cell proliferation, and explore the molecular mechanism of the biological effects of YB-1.Methods:We examined the expression of YB-1 in the 90 pairs pancreatic cancer tissues by immunohistochemistry (IHC), and analysis the relationship between YB-1 expression and degree of pancreatic cancer differentiation. western blot was used to detect the expression of YB-1 in human pancreatic cancer cell lines.Lentivirus interference was used inhibit the expression of YB-1 in pancreatic cancer. CCK-8 assay and flow cytometry were used to detect the YB-1 silencing effect on the proliferation and cell cycle of pancreatic cancer cell lines. Western blot and qPCR assay was used to investigate the changes of GSK-3? protein expression and mRNA expression in YB-1 silencing pancreatic carcinoma cell.lenti virus overexpressing of YB-1 infection was used in pancreatic cancer cell lines, western blot was used to detect change of GSK-3? expression in the YB-1 overexpressed pancreatic cancer cell lines. After use the inhibitor of GSK-3P TWS119, CCK-8 assay and flow cytometry were used to detected the impact of the cell proliferation and cell cycle by GSK-3? inhibitor in YB-1 over experssion pancreatic cancer cell lines. Application of PI3K/AKT, MEK/ERK signaling pathway inhibitor in pancreatic cancer cell lines, western blot was used to investigate signaling pathway on the regulation of YB-1.Results:YB-1 in pancreatic cancer was significantly higher than the adjacent tissues, and was positively correlated with the degree of clinical differentiation of pancreatic cancer. YB-1 was high expression in pancreatic cancer cell lines.After Lentivirus interference of YB-1 was used pancreatic cancer cells, the proliferation of pancreatic cancer was significantly inhibit, and pancreatic cancer cells in Gl phase arrest. After inhibition of YB-1, the expression of GSK-3? significantly decreased in the pancreatic cancer cells, and mRNA levels were significantly lower.After Lentivirus infection of overexpressed YB-1 in pancreatic cancer cell lines, the expression of GSK-3? was significantly increased, the proliferation was increased, the proportion of cells in G1 phase was decreased. After using a specific inhibitor of GSK-3? treatment of pancreatic cancer cell lines, the proliferation of YB-1 overexpression pancreatic cancer cell lines significantly decreased and the proportion of cells in G1 phase increase. Suggest that inhibitor of GSK-3?can reversed the effect of YB-1.PI3K/AKT and MEK/ERK signaling pathway inhibitors was used, show that YB-1 was regulated by two signaling pathway, wherein the PI3K/AKT at the transcriptional level, MEK/ERK at the translational level.Conclusions:Overexpression of YB-1 is an important mechanism that pancreatic cancer have highly malignant biological behavioris. Through the regulation of GSK-3? expression, YB-1 can promoting the progress of pancreatic cancer cell proliferation. YB-1 and GSK-3? can be a potential target for pancreatic cancer treatment.