Unraveling the tumor-promoting role of wildtype Isocitrate dehydrogenase 1 (IDH1) in human gliomas

Abstract Isocitrate dehydrogenase 1 (IDH1) mutations are discovered in most grade Ⅱ gliomas (71%-78%), grade Ⅲ gliomas (62%-78%) and secondary glioblastomas (88%), and have received lots of attention in recent years. However, the tumor-promoting role of wildtype IDH1 still need to be further investigated. In this article, we found wildtype IDH1 mRNA and protein levels were both elevated in glioma by using bioinformatic analysis, Besides, IDH1 mutation reduced the expression of wildtype IDH1 in U87-R132H cell line. Furthermore, the expression of wildtype IDH1 also increased along with the increase of clinical grades of glioma. Cell function and signaling pathways enrichment analyses were enriched in metabolic processes, phosphatase complex, TCA, DNA replication, p53 signaling pathway, Notch signaling pathway, et al. Single-cell sequencing analysis revealed that high expression of wildtype IDH1 correlated with cell cycle, metastasis, EMT, proliferation, invasion, stemness, and DNA damage. Besides, wildtype IDH1 promoted GBM cell viability, migration, and radioresistance in vitro. Wildtype IDH1 was significantly relevant with diagnosis, prognosis, and survival probability of glioma patients. Therefore, wildtype IDH1 could be an underlying target for glioma therapy.