Circular RNAs: Key Regulators of Tumor Metabolic Reprogramming and Clinical Translation.

Tumor metabolic reprogramming is a core hallmark of cancer, characterized by pathways such as aerobic glycolysis, aberrant lipid metabolism, and glutaminolysis that support rapid proliferation and immunosuppressive microenvironments. Circular RNAs (circRNAs) are highly stable, evolutionarily conserved non-coding RNAs that have emerged as critical modulators of these metabolic shifts. This review aims to systematically elucidate the roles and mechanisms of circRNAs in reprogramming tumor metabolism, and to discuss their clinical potential as biomarkers and therapeutic targets. Through mechanisms including miRNA sponging, protein interactions, regulation of mitochondrial dynamics, and modulation of metabolic enzymes, circRNAs influence key metabolic pathways by targeting glycolytic enzymes, lipid synthesis regulators, and glutaminolysis-related molecules to either facilitate or inhibit their expression. This review systematically summarizes the unique contributions of circRNAs to tumor metabolic reprogramming, highlighting key mechanisms such as regulation of peptide-encoding protein translation, mitochondrial localization function, gene promoter-targeted transcriptional regulation, and cross-pathway metabolic mediation, which underscore their distinct biological advantages and regulatory roles in tumor metabolism. The stability and tissue specificity of circRNAs make them promising diagnostic biomarkers, while their role in drug resistance mediated by metabolic reprogramming highlights their potential as therapeutic targets. Strategies such as circRNA inhibitors, mimics, and nanoparticle-based delivery systems are being explored to modulate tumor metabolism. Despite challenges including complex regulatory networks and limited manipulation tools, advances in high-throughput technologies and clinical trials hold promise for translating circRNA research into novel cancer therapies.