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In this study, we aimed to investigate the oncogenic role, underlying molecular mechanisms, and potential therapeutic value of PRMT5 in PAAD. PRMT5 was significantly upregulated in pancreatic cancer than adjacent nontumor pancreas, which was positively correlated with poor prognosis. Genetic and pharmacological inhibition of PRMT5 suppressed PAAD proliferation in vitro and in vivo, exhibiting promising therapeutic effect in vivo. Mechanistically, PRMT5 directly bound to the promoter region of c\u2010Myc and activated its transcription. Transcriptionally activated c\u2010Myc in turn inhibited proteasome\u2010mediated degradation of PRMT5 and enhanced its protein stability, resulting in increased PRMT5 expression. The maintained PRMT5 further enhanced the transcription of c\u2010Myc. In conclusion, PRMT5 forms a positive feedback loop with c\u2010Myc to promote the proliferation of pancreatic cancer. Targeting this oncogenic communication may represent a novel and potential therapeutic approach for pancreatic cancer.<\/jats:p>","DOI":"10.1002\/mco2.70150","type":"journal-article","created":{"date-parts":[[2025,5,15]],"date-time":"2025-05-15T03:32:35Z","timestamp":1747279955000},"source":"Crossref","is-referenced-by-count":3,"title":["PRMT5 Promotes Pancreatic Cancer Tumorigenesis via Positive PRMT5\/C\u2010Myc Feedback Loop"],"prefix":"10.1002","volume":"6","author":[{"given":"Fan","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Vascular Surgery Affiliated Hangzhou First People's Hospital School of Medicine Westlake University  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Affiliated Hangzhou First People's Hospital School of Medicine Westlake University  Hangzhou China"},{"name":"Key Laboratory of Integrated Traditional 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