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Although organ\u2010abundant microRNAs (miRs) regulate this protein, its role in tumor progression remains unclear. Therefore, we investigated the functional relationship between polypyrimidine tract\u2010binding protein 1\u2010associated microRNAs and this protein in pancreatic cancer to identify pancreas\u2010enriched microRNAs and explore polypyrimidine tract\u2010binding protein 1 function beyond metabolic regulation. The expression of miR\u2010216b\u20105p, which is typically pancreas\u2010enriched, was significantly downregulated in clinical pancreatic cancer samples, whereas polypyrimidine tract\u2010binding protein 1 expression was markedly upregulated. Mechanistically, miR\u2010216b\u20105p directly binds to the 3\u2032 UTR of polypyrimidine tract\u2010binding protein 1 mRNA, thereby suppressing its expression and inhibiting cancer cell proliferation. Proteomic analysis, integrated with publicly available individual\u2010nucleotide resolution UV crosslinking and immunoprecipitation data, identified thymidylate synthase as a novel downstream target of polypyrimidine tract\u2010binding protein 1, likely regulated via splicing\u2010related RNA\u2010level mechanisms. Thymidylate synthase expression was also elevated in pancreatic cancer tissues and correlated with poor prognosis. Functional assays revealed that polypyrimidine tract\u2010binding protein 1 and thymidylate synthase silencing induced cell cycle arrest. Our findings uncover a previously unrecognized miR\u2010216b\u20105p\/polypyrimidine tract\u2010binding protein 1\/thymidylate synthase regulatory axis that promotes pancreatic cancer progression and establish polypyrimidine tract\u2010binding protein 1 as a central molecular regulator of tumor biology beyond its metabolic role.<\/jats:p>","DOI":"10.1111\/cas.70402","type":"journal-article","created":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T09:36:39Z","timestamp":1777282599000},"page":"1828-1840","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Relationship Between\n                    <scp>PTBP1<\/scp>\n                    and Pancreatic Cancer Based on\n                    <scp>microRNA<\/scp>\n                    and Behavior During\n                    <scp>TYMS<\/scp>\n                    \u2010Mediated 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