Circular RNAs as regulators of epithelial‑mesenchymal transition in gliomas from molecular mechanisms to clinical applications

Abstract

Epithelial–mesenchymal transition (EMT) is a fundamental biological process that drives glioma invasion, therapeutic resistance, and malignant progression. Recent evidence highlights circular RNAs (circRNAs) as pivotal post-transcriptional regulators that orchestrate EMT through diverse molecular mechanisms. Due to their covalently closed-loop structure, circRNAs exhibit remarkable stability and function as competing endogenous RNAs by interacting with microRNAs and RNA-binding proteins to fine-tune EMT-associated signaling pathways, including TGF-β, Wnt/β-catenin, and PI3K/AKT. Several oncogenic circRNAs, such as circNEIL3 and circMAPK4, have been shown to promote EMT and glioma progression, whereas tumor-suppressive circRNAs, including circFBXW7 and circSMARCA5, counteract EMT-driven malignancy. Beyond their mechanistic roles, circRNAs are abundantly enriched in exosomes, underscoring their function as intercellular communicators within the glioma microenvironment. These unique features position circRNAs as promising biomarkers for early diagnosis and prognosis, as well as attractive therapeutic targets for molecular intervention. In this review, we summarize current advances in understanding the molecular crosstalk between circRNAs and EMT in gliomas, highlighting their translational potential and future perspectives in precision neuro-oncology.