The regulatory roles of non-coding RNAs in aerobic glycolysis and therapeutic potential in pancreatic ductal adenocarcinoma

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy with a five-year survival rate below 10%, largely due to late diagnosis and rapid metastasis. PDAC cells exhibit profound metabolic reprogramming, particularly enhanced aerobic glycolysis. Non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), have emerged as key regulators of glycolysis in PDAC, although their integrated roles and clinical relevance remain incompletely understood. MAIN FINDINGS: MiRNAs regulate glycolytic flux by targeting key enzymes and signaling pathways, thereby modulating glucose uptake and lactate production. LncRNAs promote glycolysis through pathways such as PI3K/AKT/mTOR, Wnt/β-catenin and p53, or by acting as competing endogenous RNAs. CircRNAs function as miRNA sponges or transcriptional regulators, contributing to metabolic adaptation and chemoresistance. Beyond glycolysis, ncRNAs also influence mitochondrial function, redox balance and tumor microenvironment remodeling. Clinically, several ncRNAs show promise as diagnostic and prognostic biomarkers. Therapeutic strategies targeting ncRNAs, including nano-delivery systems and RNA-based approaches, demonstrate potential for overcoming chemoresistance and enhancing treatment efficacy. CONCLUSION: NcRNAs play central roles in regulating glycolysis and metabolic adaptation in PDAC and represent promising targets for diagnosis and therapy. Further studies are required to validate key regulatory networks and translate these findings into clinical applications.