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

Zhang Li; Lanyang Gao; Yang Yang; Yue Ming; Wenrong Liu; Tingting Zhang; Zixia Ye; Fuyan Xu; Juan He; Jiao Li; Jiawei Guo; Xiaojuan Yang; Qing Zhu; Yong Peng

doi:10.34133/research.0918

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

Research (Wash D C). 2025 Oct 3:8:0918. doi: 10.34133/research.0918. eCollection 2025.

Authors

Zhang Li¹, Lanyang Gao¹, Yang Yang², Yue Ming¹, Wenrong Liu¹, Tingting Zhang¹, Zixia Ye¹, Fuyan Xu¹, Juan He¹, Jiao Li¹, Jiawei Guo¹, Xiaojuan Yang¹, Qing Zhu², Yong Peng^{1

3}

Affiliations

¹ Center for Molecular Oncology, Frontiers Science Center for Disease-related Molecular Network, State Key Laboratory of Biotherapy and Cancer Center, State Key Laboratory of Respiratory Health and Multimorbidity, West China Hospital, Sichuan University, Chengdu 610041, China.
² Division of Abdominal Tumor Multimodality Treatment, Cancer Center, Department of General Surgery, West China Hospital, Sichuan University, Chengdu 610041, China.
³ Frontiers Medical Center, Tianfu Jincheng Laboratory, Chengdu 610212, China.

Abstract

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.