Hub circRNAs in cancer: dual regulation of metastasis and immune evasion

Abstract

Circular RNAs (circRNAs) are a class of highly stable non-coding RNAs that play pivotal roles in cancer progression by concurrently modulating tumor metastasis and immune evasion. Among them, a subset termed hub circRNAs coordinates these two processes within the same tumor context through multiple regulatory mechanisms. Hub circRNAs facilitate tumor cell migration, invasion, and colonization at distant sites, while simultaneously impairing the function of immune effector cells and remodeling the tumor microenvironment into an immunosuppressive state. These dual effects can be propagated to distal microenvironments via extracellular vesicles, thereby amplifying both metastasis and immunosuppression. To organize the available evidence, we propose a provisional three-tiered stringent/convergent/network-informed (S/C/N) evidence-mapping framework that integrates evidence across studies and organizes the type and completeness of functional, mechanistic, and network-informed support. Finally, we highlight current research gaps, outline the potential of hub circRNAs as biomarkers and therapeutic targets, and discuss experimental and methodological considerations for pan-cancer investigations. This review offers a functional perspective for understanding hub circRNAs as regulators linking metastasis with immune evasion and guides future efforts to investigate their dual functions in translational settings.