Non-coding RNAs-glycolysis axis in cancer therapy resistance: Insight into mechanism to therapeutic solution.

Despite advancements in cancer therapy, including radiotherapy and chemotherapy, resistance to cancer treatment remains a significant clinical challenge. Metabolic reprogramming and dysfunctional glycolysis, a defining characteristic of cancer cells, are commonly observed in drug-resistant cancer cells. Besides glycolytic enzymes, several signaling molecules-including EGFR, HIF-1α, AMPK, and β-catenin-are involved in the regulation of glycolysis and play crucial roles in mediating resistance to cancer therapy. Numerous studies have elucidated the pivotal role of non-coding RNAs (ncRNAs), particularly microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), in the modulation of cancer drug resistance. miRNAs dually regulate glycolysis-some inhibit glycolysis to overcome therapy resistance, while others promote glycolysis, inducing resistance in cancer cells. Recent investigations have underscored the critical function of competitive endogenous RNAs (ceRNAs) in modulating glycolytic pathways, indicating circRNA/lncRNA-miRNA-mRNA as an important regulatory network in cancer therapy resistance. Exosomal ncRNAs are another mediator of cancer therapy resistance; depending on the specific ncRNAs they carry, they can either promote or suppress glycolysis. In the final section, we demonstrated that herbal medicine can successfully mitigate drug resistance in cancer by modulating the ncRNA-glycolysis axis.