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Several upregulated and downregulated microRNAs (miRNAs) are associated with invasiveness, tumorigenesis, and prognosis of PDAC. Herein, using in situ hybridization, we evaluated miR-4653-3p expression and pancreatic intraepithelial neoplasia (PanIN) and the association between miR-4653-3p expression and clinicopathological factors in PDAC patients. The miR-4653-3p target was also identified. Ninety PDAC cases, including 30 each with normal pancreatic ducts, low-grade PanINs, and high-grade PanINs, were evaluated. miR-4653-3p expression increased in the order\u2014normal pancreatic duct, low-grade PanIN, high-grade PanIN, and PDAC\u2014with no expression detected in normal pancreatic duct. High expression significantly correlated with advanced pathological T stage, lymph node metastasis, advanced Union for International Cancer Control stage, perineural invasion, venous involvement, and shorter overall and disease-specific survival. Homeodomain Interacting Protein Kinase 2 (HIPK2) was identified as a miR-4653-3p target based on mRNA microarray analysis and database screening. In MIA PaCa-2 cells, miR-4653-3p significantly downregulated HIPK2 expression. HIPK2 expression, unlike that of miR-4653-3p, decreased in the order\u2014normal pancreatic duct, low-grade PanIN, high-grade PanIN, and PDAC. Low HIPK2 expression was associated with shorter overall and disease-specific survival in PDAC patients. Thus, miR-4653-3p associates with tumorigenesis and worse prognosis, partly by reducing HIPK2 expression.<\/jats:p>","DOI":"10.1038\/s41598-022-22950-2","type":"journal-article","created":{"date-parts":[[2022,10,26]],"date-time":"2022-10-26T10:05:36Z","timestamp":1666778736000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["miR-4653-3p overexpression is associated with a poor prognosis of pancreatic ductal adenocarcinoma via HIPK2 downregulation"],"prefix":"10.1038","volume":"12","author":[{"given":"Kenichi","family":"Hirabayashi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaki","family":"Miyazawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yumi","family":"Takanashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masashi","family":"Morimachi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aya","family":"Kawanishi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsubasa","family":"Saika","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshio","family":"Nakagohri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoya","family":"Nakamura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,10,26]]},"reference":[{"key":"22950_CR1","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.pan.2014.10.001","volume":"15","author":"M Hidalgo","year":"2015","unstructured":"Hidalgo, M. et al. 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