PRKCB Inhibits Glioma Progression By Enhancing Ferroptosis

Background:Glioma,as the most common primary brain tumor in adults,has a poor prognosis and the highest mortality of central nervous system tumors.It is of great significance to explore the molecular mechanism of glioma development.Protein kinase C-β(PRKCB),a member of the protein kinase family,is involved in a variety of cellular signaling pathways.Previous studies have confirmed that PRKCB may be one of the core factors affecting the development of glioma.Ferroptosis is a newly discovered programmed cell death mode,which plays an important role in the occurrence and development of a variety of human cancers.Studies have shown that protein kinase C-β(PRKCB)can induce ferroptosis in cancer by phosphorylation of ACSL4,thus inhibiting the occurrence and development of cancer.However,the effect of PRKCB on glioma has not been reported.Objective:To explore the role of PRKCB in the occurrence and development of glioma,and further study the mechanism of regulation of glioma cell proliferation mediated by PRKCB,in order to find new targets for glioma treatment.Method:1.To analyze the difference of PRKCB expression in non-tumor brain tissue and glioma tissue and the effect on prognosis of patients.The differential gene data of tumor samples in TCGA、CGGA databases and the corresponding non-tumor samples in GTEx databases were obtained.The glioma and non-tumor brain tissues collected were sequenced by RNA-Seq to detect the differential expression of PRKCB.The survival analysis and correlation analysis of clinical indicators were performed using software R-4.1.0.2.Glioblastoma(GBM)cell proliferation and migration experiment.U251MG,U118MG and LN229 cell lines were transfected with PRKCB overexpression plasmid and no-load plasmid.Cell proliferation was detected and plotted using CCK-8 for individual cell types.The effect of overexpression of PRKCB on GBM cell migration was detected by Transwell cell culture with single cell types.3.Correlation between PRKCB and mortality potential index(FPI)and genes related to ferroptosis.According to the method of researchers in Sun Yat-sen University,FPI of each sample in TCGA database was obtained,and Pearson correlation coefficient was used to test the correlation between PRKCB and FPI.In GlioVis platform obtained the correlation between PRKCB and some classical ferroptosis genes.4.To detect the effect of PRKCB overexpression on ferroptosis of GBM cell line.The cells were treated with 5mM Erastin respectively for 48h.The proliferation status was detected by CCK-8 and the proliferation curve was plotted.Results:1.Open database and tumor tissue RNA-seq analysis demonstrated low expression of PRKCB in human glioma.2.Bioinformatic analysis of open database demonstrated that low expression of PRKCB in tumor tissues of glioma patients predicted poor prognosis.3.In vitro cell experiments showed that the overexpression of PRKCB inhibited the proliferation and migration of GBM cells.4.Bioinformatic analysis of open database demonstrated that the expression of PRKCB in tumor tissues of glioma patients was positively correlated with the degree of ferroptosis.5.In vitro cell experiments verified that PRKCB could inhibit the proliferation of GBM cells by enhancing ferroptosis.Conclusions:1.Low expression of PRKCB in glioma tissues is associated with shorter survival of glioma patients and predicts poor prognosis of glioma patients.Overexpression of PRKCB can inhibit the proliferation and migration of GBM cells.2.The expression of PRKCB inhibits the development of glioma by enhancing ferroptosis.