Circular RNAs in glioma progression: Fundamental mechanisms and therapeutic potential: A review

Gliomas are the most common primary malignant brain tumors, characterized by aggressive invasion, limited therapeutic options, and poor prognosis. Despite advances in surgery, radiotherapy, and chemotherapy, the median survival of glioma patients remains disappointingly low. Therefore, identifying glioma-associated therapeutic targets and biomarkers is of significant clinical importance. Circular RNAs (circRNAs) are a class of naturally occurring long non-coding RNAs (lncRNAs), notable for their stability and evolutionary conservation. Increasing evidence indicates that circRNA expression is dysregulated in gliomas compared to adjacent non-tumor tissues and contributes to the regulation of glioma-related biological processes. Furthermore, numerous circRNAs function as oncogenes or tumor suppressors, mediating glioma initiation, progression, and resistance to temozolomide (TMZ). Mechanistically, circRNAs regulate glioma biology through diverse pathways, including acting as miRNA sponges, binding RNA-binding proteins (RBPs), modulating transcription, and even encoding functional peptides. These features highlight the potential of circRNAs as diagnostic and prognostic biomarkers, as well as therapeutic targets for glioma. This review summarizes the dysregulation and functions of circRNAs in glioma and explores key mechanisms through which they mediate tumor progression, including DNA damage repair, programmed cell death (PCD), angiogenesis, and metabolic reprogramming. Our aim is to provide a comprehensive perspective on the multifaceted roles of circRNAs in glioma and to highlight their potential for translational application in targeted therapy.