# The Role of Circular RNA in the Progression of Gliomas and Its Potential Clinical Applications

## TL;DR

This review explores how circular RNAs (circRNAs) contribute to glioma progression and their potential as biomarkers and therapeutic targets for improving treatment outcomes.

## Contribution

The paper systematically reviews circRNA mechanisms and their clinical relevance in gliomas, emphasizing their stability and potential for targeted therapies.

## Key findings

- CircRNAs are stable, tissue-specific molecules that interact with miRNAs and RBPs, influencing glioma progression.
- Dysregulated circRNAs are linked to glioma proliferation, metastasis, and drug resistance, offering potential for targeted therapies.
- Exosomes can transport circRNAs across the blood–brain barrier, suggesting their use in delivering therapeutic agents to brain tumors.

## Abstract

The treatment outcomes and prognosis for glioma patients remain unsatisfactory, and a comprehensive understanding of the mechanisms underlying glioma development and progression is essential for improving therapeutic strategies. It has been demonstrated that the etiology of gliomas involves differential expression of various circular RNAs (circRNAs). This review outlines the intrinsic biological mechanisms of circRNAs, then presents many circRNAs that contribute to tumor progression through different pathways, emphasizing their potential as biomarkers. Moreover, this review explores the correlations among circRNAs, gliomas, and clinical drug responses, integrating clinical challenges to highlight the diagnostic, prognostic, and therapeutic relevance of circRNAs. Therefore, this review emphasizes that circRNAs, due to their unique advantages and high structural stability, may serve as promising targets for future glioma treatment by blocking drug-resistance transmission among tumor cells, restoring drug sensitivity, encoding functional proteins for immunotherapy, and regulating blood–brain barrier permeability to therapeutic agents.

Circular RNAs (circRNAs) are single-stranded noncoding RNAs with a covalently closed loop structure. They are known for their stability, abundance, and highly conserved nature. Their expression is often specific to tissues or developmental stages. They interact with microRNAs (miRNAs) and RNA-binding proteins (RBPs) and they undergo N6-methyladenosine (m6A) modifications, further affecting gene transcription and translation. Increasing evidence over the past decades has revealed that dysregulated circRNA expression is associated with various neurological disorders, particularly the glioma, one of the most malignant tumors with a poor prognosis. Due to the presence of the blood–brain barrier (BBB) and drug resistance, conventional therapeutic approaches have shown limited efficacy. Recently, increasing attention has been directed toward precisely targeted therapies, with circRNAs emerging as promising molecules for cancer treatment. Studies indicate that circRNAs play a key role in glioma proliferation and metastasis. Substantial evidence indicates that exosomes can package circRNAs and facilitate their transport across the BBB into brain tissue, highlighting the potential of circRNAs as therapeutic targets for glioma. This review summarizes circRNAs’ functional mechanisms, clinical application relevance, and current limitations. It offers future research directions in this evolving field, aiming to encourage further research on circRNAs’ therapeutic applications and contribute to the development of novel glioma-treatment strategies.