Exosome-derived miR-21-5p promotes pancreatic cancer progression via ABCD2 gene

Abstract Pancreatic cancer is an aggressive malignancy with a dismal prognosis, and the underlying molecular mechanisms remain only partially understood. This study aimed to clarify the role of microRNA-21-5p (miR-21-5p) in pancreatic cancer progression and to investigate the associated mechanisms. We found that miR-21-5p was significantly elevated in pancreatic cancer tissues, and its high expression correlated with poorer patients’ prognosis. Functional assays revealed that miR-21-5p enhanced the proliferation, migration, and invasive capabilities of pancreatic cancer cells. Through bioinformatics analysis and experimental validation, we discovered ATP-binding cassette transporter D2 (ABCD2) as a novel direct target gene of miR-21-5p. ABCD2 expression was significantly downregulated in pancreatic cancer tissues, and its low expression was associated with reduced patient survival. Mechanistically, miR-21-5p inhibited ABCD2 transcription and translation by directly targeting its 3'UTR, a process facilitated by exosome delivery. Importantly, overexpression of ABCD2 effectively reversed the pro-oncogenic effects of miR-21-5p. Our findings establish the critical role of the miR-21-5p/ABCD2 axis in pancreatic cancer progression and highlight the tumor-suppressive function of ABCD2. ABCD2 may represent a promising therapeutic target and a potential site for the diagnosis and treatment of pancreatic cancer.