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Extracellular vesicles (EVs) are key mediators of inter\u2010organ communication. Here, EVs and EV\u2010microRNAs (miRNAs) are identified as mediate PDAC\u2010skeletal muscle communication. EVs are isolated from PDAC patients, mouse models, patients\u2010derived organoids, and mouse pancreatic cancer cells. Plasma\u2010derived EVs from PDAC patients or mice are observed to remarkably induced muscle wasting in vitro and in vivo. Depletion of miRNA cargo in these EVs significantly alleviates their detrimental effects on skeletal muscles. Deep RNA sequencing is conducted to profile differentially expressed miRNAs in plasma EVs from patients with or without PDAC. The findings reveal that the expression of miR\u2010223\u20105p expression in PDAC patients\u2019 plasma EVs is negatively associated with the 3\u2010year overall survival. Mechanistic studies show that miR\u2010223\u20105p contributes to reduced METTL14 transcription by targeting MAFA, associated with decreased m\n                    <jats:sup>6<\/jats:sup>\n                    A methylation in skeletal muscles and muscle wasting. This study highlights the absorption of miRNA in PDAC\u2010derived EVs by skeletal muscles and reveals a previously unrecognized function of PDAC\u2010derived EV\u2010miR\u2010223\u20105p in tumor\u2010muscle inter\u2010organ communication, offering novel insight into EV\u2010miR\u2010223\u20105p\u2010based diagnostic and therapeutic strategies for PDAC patients with sarcopenia upon further validation.\n                  <\/jats:p>","DOI":"10.1002\/advs.202504064","type":"journal-article","created":{"date-parts":[[2025,7,3]],"date-time":"2025-07-03T02:38:45Z","timestamp":1751510325000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Pancreatic Cancer\u2010Derived Extracellular Vesicles Enriched with miR\u2010223\u20105p Promote Skeletal Muscle Wasting Associated with 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