Circular RNAs in cervical cancer: from ceRNA networks to epitranscriptomic regulation, immune modulation, and...

Cervical cancer progression is driven not only by persistent high-risk human papillomavirus infection but also by multilayered post-transcriptional regulatory networks that reshape tumor cell behavior and the tumor microenvironment. Among these regulators, circular RNAs (circRNAs) have emerged as pivotal modulators of oncogenic signaling. Initially characterized as competing endogenous RNAs (ceRNAs), circRNAs were shown to promote cervical cancer growth, invasion, and chemoresistance by derepressing key oncogenic targets. However, recent evidence expands this paradigm, revealing that circRNAs are subject to epitranscriptomic modification and function as dynamic scaffolds integrating RNA-binding proteins, translational machinery, inflammatory signaling, and metabolic pathways. In cervical cancer, m6A-dependent regulation and reader-mediated translational control enhance circRNA stability and amplify oncogenic outputs, linking RNA modification to metabolic reprogramming and hypoxia adaptation. Concurrently, circRNAs modulate inflammatory cascades such as IL6/JAK/STAT3 and NF-κB, contributing to immune suppression and tumor microenvironment remodeling. These tumor-intrinsic and immune-extrinsic mechanisms converge on metastatic reprogramming, enabling lipid metabolic flexibility, lymphangiogenesis, autophagy activation, and therapeutic resistance. This review synthesizes current evidence to propose a unified regulatory landscape in which circRNAs function as central nodes connecting ceRNA circuits, epitranscriptomic modulation, immune signaling, and metabolic plasticity. Unlike previous reviews that primarily summarized circRNA-mediated ceRNA networks, canonical oncogenic pathways, or biomarker potential, this review adopts a systems-level perspective and critically integrates epitranscriptomic regulation, RNA-binding protein interactions, immune-inflammatory signaling, metabolic plasticity, and metastatic reprogramming. We further distinguish directly validated cervical cancer mechanisms from emerging or hypothetical regulatory layers, thereby providing a clearer conceptual framework for future mechanistic and translational studies.