Abstract
BACKGROUND: RNA editing by adenosine deaminases acting on RNA (ADARs) converts adenosines to inosines (A-to-I) in RNA, that alters gene expression and generates protein diversity. Dysregulation of A-to-I editing has been found associated with a number of nervous system diseases. However, the role of ADAR3, a brain specific high expression adenosine deaminase, in gliomas has rarely been investigated. In this study we illuminated the clinical significance and molecular features of ADAR3 in patients with glioma. METHODS: 309 glioma samples from Chinese Glioma Genome Atlas were enrolled into this study. In validation sets, 601 glioma samples in TCGA, 410 glioma samples in REMBRANDT and 258 glioma samples in GSE16011 were obtained. Relationships between ADAR3 expression and prognosis-related genomic alteration, outcome and gene ontology analysis were investigated. Moreover, the characteristic of GRIA2(Q607R) editing in gliomas has been investigated. Graphpad Prism 5.0, SPSS 16.0 and R language were used to perform statistical analysis and graphical work. RESULTS: ADAR3 expression was down regulated along with glioma grade progression in CGGA dataset. ADAR3 was characteristically highly expressed in neural subtype and IDH1/2 mutant preference. Moreover, high expression of ADAR3 predicted a better prognosis in lower-grade glioma (LGG) patients and multivariate analysis suggested ADAR3 expression was an independent prognostic indicator. The results of the three other validation datasets showed similar findings. Bioinformatics analyses suggested that ADAR3 may play a role in the malignant transformation of glioma cells by affecting cell proliferation, angiogenesis or cell adhesion. Furthermore, the editing level of GRIA2(Q607R) was significantly correlated with ADAR3 expression. CONCLUSIONS: Our study demonstrated the clinical and molecular characterization of ADAR3 in glioma development and progression. ADAR3 expression was negatively associated with tumor malignant in the overall glioma patients. And it was a favorable independent prognostic indicator of LGG patients. ADAR3 appeared to act as a tumor suppressor in glioma cells. Therefore, ADAR3 represented a potential therapeutic target and useful prognostic factor for glioma patients.