A Circular RNA Promotes Tumor Metastasis through Stabilizing MSI2 Protein in Pancreatic Ductal Adenocarcinoma

Tumor metastasis is a major contributor for mortality in patients with pancreatic ductal adenocarcinoma (PDAC). While circular RNAs (circRNAs) have emerged as pivotal regulators of tumor progression and metastasis, their functional roles in PDAC remain poorly understood. Through comprehensive circRNA profiling of 10 pairs of PDAC tumors and adjacent normal tissues, we identified circPRKD3 (hsa_circ_0000992) as being substantially up-regulated in malignant specimens. Functional characterization demonstrated that circPRKD3 overexpression potently enhanced cellular migration, invasion, and metastatic capacity in vitro and in vivo, whereas its knockdown produced opposite phenotypic effects. Mechanistic investigations revealed that circPRKD3 directly interacted with the oncogenic RNA-binding protein Musashi-2, protecting it from β-TRCP-mediated ubiquitination and subsequent proteasomal degradation. Clinical correlation analysis revealed a close association between elevated circPRKD3 expression and shorter survival of PDAC patients. Notably, we validated the translational potential of circPRKD3 as a liquid biopsy marker, showing that serum detection, when combined with conventional biomarkers (CA19-9, CEA, and CA125), dramatically improved diagnostic performance. These findings not only delineate a novel circRNA-mediated regulatory axis in PDAC metastasis but also identify circPRKD3 as a promising diagnostic and prognostic biomarker.