The Glioblastoma CircularRNAome

Abstract

Glioblastoma remains one of the most aggressive cancers of the brain, warranting new methods for early diagnosis and more efficient treatment options. Circular RNAs (circRNAs) are rather new entities with increased stability compared to their linear counterparts that interact with proteins and act as microRNA sponges, among other functions. Herein, we provide a critical overview of the recently described glioblastoma-related circRNAs in the literature, focusing on their roles on glioblastoma cancer cell proliferation, survival, migration, invasion and metastasis, metabolic reprogramming, and therapeutic resistance. The main roles of circRNAs in regulating cancer processes are due to their regulatory roles in essential oncogenic pathways, including MAPK, PI3K/AKT/mTOR, and Wnt, which are influenced by various circRNAs. The present work pictures the wide implication of circRNAs in glioblastoma, thus highlighting their potential as future biomarkers and therapeutic targets/agents.

Current advances in circular RNA detection and investigation methods: Are we running in circles?

“…Other structural aspects, such as the lack of free ends, offers increased stability and resistance to exonuclease (Shi et al, 2022;Xiao & Wilusz, 2019). In addition, studies reporting on their tissue-specific accumulation and expression (Patop et al, 2019) have put them into the spotlight for extensive investigations as potential biomarkers in multiple pathologies, especially oncological ones (Drula et al, 2020(Drula et al, , 2020Kristensen et al, 2022;Tirpe et al, 2023). A crucial functional aspect that stirred the interest for their investigation is their single-stranded structure, which provides a platform for circRNAs to harbor multiple miRNA-binding sites (or miRNA response elements [MREs]), attributing them as "competing endogenous RNAs" (ceRNAs) (Panda, 2018) but also allowing the interaction with RBPs (Huang et al, 2020;Zang et al, 2020).…”