Tumor-Promoting Function Of Pimreg In Glioma By Activating The Beta-Catenin Pathway

Glioma is the most common primary brain tumor in adults with an adverse prognosis and obscure pathogenesis. PICALM interacting mitotic regulator protein (PIMREG) functions as an oncogene in multiple types of cancer, but its function in glioma remains unknown. The Gene Expression Profiling Interactive Analysis 2 (GEPIA2, http://gepia2.cancer-pku.cn/# index) showed that PIMREG expression in the glioma tissues was higher than that in normal brain tissues. Herein, cell counting kit-8 assay and flow cytometry analysis exhibited that overexpression of PIMREG significantly promoted the proliferation of glioma cells and the transition from G1 phase of the cell cycle to S phase. Wound-healing and transwell assays showed that overexpression of PIMREG markedly enhanced the migration and invasion of glioma cells. Western blot analysis revealed that overexpression of PIMREG increased the expression of cyclin D1, cyclin E, Vimentin, matrix metalloproteinase (MMP)-2, and MMP-9, but reduced the expression of E-cadherin. In addition, overexpression of PIMREG activated the beta-catenin signaling pathway, as evidenced by the increased total and nuclear expression of beta-catenin and the up-regulated expression of its downstream target c-myc. Furthermore, immunofluorescence staining further indicated the increased nuclear translocation of beta-catenin in PIMREG-overexpressing cells. However, knockdown of PIMREG exerted opposite effects on glioma cells. Blockade of the beta-catenin signaling by ICG-001 markedly impeded the promoting effects of PIMREG on glioma cell proliferation and invasion. In conclusion, PIMREG acts as a tumor promoter in glioma at least partly via activating the beta-catenin signaling pathway. This study provides new insights into the molecular mechanism for glioma pathogenesis and treatment.