LRP5 enhances glioma cell proliferation by modulating the MAPK/p53/cdc2 pathway.

Background: Glioma is a malignant neoplasm with generally poor prognosis and the treatment options and effective drugs are very limited. LRP5, a member of the low-density lipoprotein receptor (LDLR) gene family, has been reported to regulate the progression of various cancers such as gastric and colorectal cancer. However, the function of LRP5 in glioma has not been elucidated. The objective of this study is to explore the influence of LRP5 in glioma cell proliferation and its potential molecular mechanisms. Methods: LRP5 expression in glioma was assessed through bioinformatics analysis, and validation was conducted using clinical glioma tissues. Glioma cell lines with reduced LRP5 expression were established through RNA interference. A series of experiments such as cell proliferation assay, flow cytometry analysis, and Western blotting were used to determine the role of LRP5 in glioma cell proliferation, cell cycle progression, and the underlying mechanisms. Results: LRP5 was found to be upregulated in glioma tissues and exhibited significant variations across various subtypes of glioblastoma (GBM). When differentiating between normal individuals and glioma patients, the area under the receiver operating characteristic curve (ROC) for LRP5 was determined to be 0.981. Downregulating the expression of LRP5 in glioma cells can weaken their proliferative ability and reduce the number of cell colonies. There were more cells arrested in the G2/M phase of the cell cycle. The protein levels of phospho-p53 (p-p53), p21Cip1, and phospho-cdc2 (p-cdc2) were elevated. Moreover, LRP5 down-regulation suppressed the phosphorylation of the mitogen-activated protein kinase (MAPK) family members, JNK and p38 MAPK. Consistent results with those mentioned above can be achieved by using an LRP5 antagonist named DKK-1. Conclusion: This research has identified that LRP5 may promote glioma proliferation by influencing the G2/M transition and the activation of the MAPK/p53/cdc2 pathways, suggesting its value as a potential molecular target for glioma diagnosis and treatment.