Transcriptome-wide analysis of circRNA and RBP profiles and their molecular and clinical relevance for GBM

Abstract

Glioblastoma (GBM) is the most aggressive and lethal type of glioma, characterized by aberrant expression of non-coding RNAs including circular RNAs (circRNAs). They might impact cellular processes by interacting with other molecules – like microRNAs or RNA-binding proteins (RBPs). The diagnostic value of circRNAs and circRNAs/RBPs complexes is still largely unknown. To explore circRNAs and RBPs transcripts expression in GBM, we performed and further analyzed RNA-seq data from GBM patients’ primary and recurrent tumor samples. We identified circRNAs differentially expressed in primary tumors, the circRNA progression markers in recurrent GBM samples as well as the expression profile of RBP transcripts. Subsequent analysis allowed us to generate a comprehensive catalog of circRNA-RBP interactions regarding both the RBPs sequestration by circRNA as well as the RBPs involvement in circRNA biogenesis. Furthermore, we demonstrated the clinical potential of circRNAs and RBPs in GBM and proposed them as the stratification markers in the de novo assembled tumor subtypes. Therefore, our transcriptome-wide study specified circRNA-RBP interactions that could play a significant regulatory role in gliomagenesis and GBM progression.