Exosome‐Associated miR‐21‐5p Promotes Pancreatic Cancer Progression Via ABCD2

Background Pancreatic cancer is an aggressive malignancy with a poor prognosis, and its molecular mechanisms remain incompletely understood. MicroRNA‐21‐5p (miR‐21‐5p) has been implicated in tumor progression, but its precise role and downstream targets in pancreatic cancer require further clarification. This study aimed to investigate the oncogenic function of miR‐21‐5p, identify its direct target ATP‐binding cassette transporter D2 (ABCD2), and assess their clinical relevance. Methods Expression levels of miR‐21‐5p were initially evaluated in a small exploratory plasma cohort of pancreatic cancer patients and healthy controls. Associations with patient prognosis were analyzed using the TCGA‐PAAD public dataset. In vitro assays were conducted to assess the effects of miR‐21‐5p on pancreatic cancer cell proliferation, migration, and invasion. Bioinformatic prediction and dual‐luciferase reporter assays were used to identify ABCD2 as a target gene. Exosome‐mediated delivery of miR‐21‐5p was examined, and ABCD2 overexpression was applied to assess its ability to counteract miR‐21‐5p–induced effects. Results MiR‐21‐5p was upregulated in pancreatic cancer samples, and high expression was associated with a poor prognosis in TCGA data. ABCD2 expression was downregulated in tumors, with low expression correlating with reduced survival. Mechanistically, miR‐21‐5p directly bound the 3′ UTR of ABCD2, suppressing its transcription and translation, a process partially mediated by exosomal transfer. Overexpression of ABCD2 attenuated the protumorigenic effects of miR‐21‐5p in vitro, highlighting a functional hsa‐miR‐21‐5p/ABCD2 regulatory axis.