Luoluo Wang, Xiang Wu, Yi Ruan, Xueming Zhang, Gong Cheng, Xinhua Zhou
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 circ_0001535 overexpression. Downregulation of circ_0001535 and HIPK2 was observed in PC, whereas miR-126-5p showed elevated expression. Curcumin treatment significantly upregulated circ_0001535 expression and suppressed malignant cellular behaviours. Mechanistically, circ_0001535 modulates HIPK2 expression by sponging miR-126-5p. Notably, overexpression of circ_0001535 enhanced the antitumor effects of curcumin in vivo. These findings suggest that curcumin inhibits PC progression by upregulating circ_0001535, which modulates the miR-126-5p/HIPK2 signalling axis. This study provides novel mechanistic insights into the therapeutic potential of curcumin in PC treatment.