Curcumin suppresses pancreatic cancer progression and glycolysis by modulating the circ₀001535/miR-126-5p/HIPK2 axis

Although curcumin exerts anticancer effects in pancreatic cancer (PC) through various molecular pathways, its regulatory mechanisms mediated by non-coding RNA networks remain incompletely understood. This study sought to elucidate its functional role in PC progression, with particular focus on circRNA-driven regulatory networks. Cellular functions including viability, clonogenicity, migration, and invasion were examined through CCK-8, colony formation, and Transwell assays. Commercial kits and Seahorse XP 96 were used to measure glycolytic activity, while RT-qPCR and Western blot were applied to detect RNA and protein expression levels. Bioinformatic tools were utilised to predict possible circRNA-miRNA interactions, which were then experimentally verified using dual-luciferase reporter assays and RIP. In vivo tumour suppression was evaluated in xenografted mouse models treated with curcumin and/or circ₀001535 overexpression. Downregulation of circ₀001535 and HIPK2 was observed in PC, whereas miR-126-5p showed elevated expression. Curcumin treatment significantly upregulated circ₀001535 expression and suppressed malignant cellular behaviours. Mechanistically, circ₀001535 modulates HIPK2 expression by sponging miR-126-5p. Notably, overexpression of circ₀001535 enhanced the antitumor effects of curcumin in vivo. These findings suggest that curcumin inhibits PC progression by upregulating circ₀001535, which modulates the miR-126-5p/HIPK2 signalling axis. This study provides novel mechanistic insights into the therapeutic potential of curcumin in PC treatment.