The Crosstalk and Clinical Implications of CircRNAs and Glucose Metabolism in Gastrointestinal Cancers

SIMPLE SUMMARY: Glucose metabolism reprogramming is a hallmark of cancer. In tumor cells, the majority of glucose is converted to lactate despite the presence of sufficient oxygen and functional mitochondria, thereby contributing to cancer progression and immunosuppression. Circular RNAs are a type of endogenous single-stranded RNAs characterized by covalently circular structures. Recent studies have revealed that circular RNAs regulate glucose metabolism in various cancers. In this review, we discuss the molecular mechanisms by which circular RNAs regulate glucose metabolism in gastrointestinal cancers. Furthermore, we consider the potential of glucose-metabolism-associated circular RNAs as new biomarkers and therapeutic targets for gastrointestinal cancers. ABSTRACT: The majority of glucose in tumor cells is converted to lactate despite the presence of sufficient oxygen and functional mitochondria, a phenomenon known as the “Warburg effect” or “aerobic glycolysis”. Aerobic glycolysis supplies large amounts of ATP, raw material for macromolecule synthesis, and also lactate, thereby contributing to cancer progression and immunosuppression. Increased aerobic glycolysis has been identified as a key hallmark of cancer. Circular RNAs (circRNAs) are a type of endogenous single-stranded RNAs characterized by covalently circular structures. Accumulating evidence suggests that circRNAs influence the glycolytic phenotype of various cancers. In gastrointestinal (GI) cancers, circRNAs are related to glucose metabolism by regulating specific glycolysis-associated enzymes and transporters as well as some pivotal signaling pathways. Here, we provide a comprehensive review of glucose-metabolism-associated circRNAs in GI cancers. Furthermore, we also discuss the potential clinical prospects of glycolysis-associated circRNAs as diagnostic and prognostic biomarkers and therapeutic targets in GI cancers.