Circular RNAs Drive Metabolic Reprogramming in Gastric Cancer, Offering Biomarker and Therapeutic Potential

Gastric cancer (GC), originating from gastric mucosal epithelium, remains a significant threat to patient survival, driven by factors like Helicobacter pylori infection and genetic susceptibility. A hallmark of tumorigenesis is metabolic reprogramming, where cancer cells adapt their energy metabolism to support proliferation, invasion, metastasis, and drug resistance. Circular RNAs (circRNAs), stable non-coding RNAs with a covalently closed structure, are differentially expressed in tumor cells and are increasingly recognized for their role in facilitating tumor progression and influencing cellular metabolism.

This comprehensive review systematically summarized the current understanding of how circular RNAs (circRNAs) mediate diverse metabolic modes during the initiation and progression of gastric cancer (GC). The authors elucidated the intricate mechanisms by which circRNAs contribute to tumor metabolic remodeling, focusing on their regulation of key enzymes and transporters in metabolic pathways. Furthermore, the review discussed the significant potential of circRNAs as novel biomarkers for GC diagnosis, prognosis, and therapeutic response prediction, aiming to provide a theoretical foundation for future therapeutic strategies.

Circular RNAs (circRNAs) are widely implicated in gastric cancer (GC) progression by orchestrating metabolic reprogramming, enabling cancer cells to meet their high energy demands. They exert their regulatory functions through multiple mechanisms, including acting as microRNA sponges, binding to proteins, facilitating short peptide translation, and undergoing N6-methyladenosine modification. These actions collectively modulate the synthesis or degradation of crucial metabolites and regulate key enzymes and transporters involved in various metabolic pathways. For instance, specific circRNAs can enhance glycolysis or glutaminolysis, pathways critical for tumor growth and survival. > CircRNAs meet tumor energy demands by regulating key enzymes and transporters involved in metabolic pathways, modulating synthesis or degradation of metabolites. This intricate interplay underscores their pivotal role in adapting cellular metabolism to support proliferation, invasion, metastasis, and drug resistance in GC.