Circular RNA hsa_circ_0003472 Promotes Pancreatic Ductal Adenocarcinoma Progression and Gemcitabine Resistance Via the mir-1253/ERCC1 Axis

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies with limited therapeutic options. Circular RNAs (circRNAs) have emerged as critical regulators of cancer progression; however, the functional role of hsa_circ_0003472 in PDAC remains unexplored. Expression of hsa_circ_0003472 was assessed in 30 paired PDAC and adjacent normal tissues and pancreatic cancer cell lines using quantitative RT-PCR. Loss-of-function experiments were performed to evaluate effects on proliferation (CCK-8, EdU), apoptosis (TUNEL, Western blot), migration, and invasion (Transwell assays). Gemcitabine sensitivity was determined by IC50 analysis. Bioinformatic prediction and dual-luciferase reporter assays identified the downstream regulatory axis. Xenograft mouse models validated findings in vivo. hsa_circ_0003472 was significantly upregulated in PDAC tissues and cell lines. Silencing hsa_circ_0003472 inhibited proliferation, migration, and invasion while promoting apoptosis and enhancing gemcitabine sensitivity. Mechanistically, hsa_circ_0003472 functioned as a competing endogenous RNA by sponging miR-1253, thereby relieving suppression of excision repair cross-complementing group 1 (ERCC1). Rescue experiments confirmed that the oncogenic effects of hsa_circ_0003472 were mediated through the miR-1253/ERCC1 axis. In vivo, hsa_circ_0003472 knockdown significantly reduced tumor growth and recapitulated molecular changes observed in vitro. hsa_circ_0003472 promotes PDAC progression and chemoresistance through the miR-1253/ERCC1 regulatory axis, representing a potential therapeutic target for this devastating malignancy.