KDELR2 is an unfavorable prognostic biomarker and regulates CCND1 to promote tumor progression in glioma

Background: The KDEL receptor is a seven-transmembrane-domain protein, which plays a key role in ER quality control and in the ER stress response, KDELR2 involved in regulation of cellular functions, including cell proliferation, survival, promotes glioblastoma tumorigenesis. The aim of this study was to investigate the clinicpathological value and biological role of KDELR2 in glioma. Methods: We studied the expression of KEDLR2 and its association with the prognosis through the TCGA, CGGA, and GSE16011 database. To explore the role of KDELR2 in glioma, KDELR2 siRNA was constructed and transfected into U87 glioma cells. CCK-8, colony formation and Transwell assays were used to investigate the roles of KDELR2 on GBM cell proliferation. We further studied the effect of KDELR2 on tumorigenesis in animal model. Additionally, flow cytometry was used to monitor the changes in the cell cycle and apoptosis following transfection with KDELR2 siRNA. We applied GeneChip primeview expression array to analysis the differential gene expression profiling. Ingenuity Pathway Analysis to show that KDELR2 has a significant impact in canonical pathway in cell cycle regulation and participate in multiple pathways. And we detected the cell cycle proteins CCND1 expression by Western blot analysis. Results: Our results showed that KDELR2 was up-regulated in glioma tissue and cell lines. Knockdown KDELR2 was able to reduce cell viability, promote cell cycle arrest at the G1 phase, and induce apoptotic cell death. Moreover, our results suggested that KDELR2 regulated the cellular functions of U87 cells by targeting CCND1. Therefore, we demonstrated that KDELR2 is a novel biomarker in glioma. Conclusions: KDELR2 is highly expressed in human glioma tissues and cell lines, a higher expression of KDELR2 is associated with a poor prognosis of glioma patients. Moreover, KDELR2 regulated the cellular functions of U87 cells by targeting CCND1. The KDELR2/CCND1 axis may provide a new therapeutic target for the treatment of glioma and deepen our understanding of glioma mechanisms.