{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T23:33:10Z","timestamp":1774481590745,"version":"3.50.1"},"reference-count":46,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2023,2,21]],"date-time":"2023-02-21T00:00:00Z","timestamp":1676937600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81974381"],"award-info":[{"award-number":["81974381"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2023,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Pancreatic cancer (PAAD) is a highly malignant tumour characterized of high mortality and poor prognosis. Huntingtin\u2010interacting protein 1\u2010related (HIP1R) has been recognized as a tumour suppressor in gastric cancer, while its biological function in PAAD remains to be elucidated. In this study, we reported the downregulation of HIP1R in PAAD tissues and cell lines, and the overexpression of HIP1R suppressed the proliferation, migration and invasion of PAAD cells, while silencing HIP1R showed the opposite effects. DNA methylation analysis revealed that the promoter region of HIP1R was heavily methylated in PAAD cell lines when compared to the normal pancreatic duct epithelial cells. A DNA methylation inhibitor 5\u2010AZA increased the expression of HIP1R in PAAD cells. 5\u2010AZA treatment also inhibited the proliferation, migration and invasion, and induced apoptosis in PAAD cell lines, which could be attenuated by HIP1R silencing. We further demonstrated that HIP1R was negatively regulated by miR\u201092a\u20103p, which modulates the malignant phenotype of PAAD cells in vitro and the tumorigenesis in vivo<jats:italic>.<\/jats:italic> The miR\u201092a\u20103p\/HIP1R axis could regulate PI3K\/AKT pathway in PAAD cells. Taken together, our data suggest that targeting DNA methylation and miR\u201092a\u20103p\u2010mediated repression of HIP1R could serve as novel therapeutic strategies for PAAD treatment.<\/jats:p>","DOI":"10.1111\/jcmm.17612","type":"journal-article","created":{"date-parts":[[2023,2,22]],"date-time":"2023-02-22T04:47:48Z","timestamp":1677041268000},"page":"788-802","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["DNA methylation and miR\u201092a\u20103p\u2010mediated repression of HIP1R promotes pancreatic cancer progression by activating the PI3K\/AKT pathway"],"prefix":"10.1111","volume":"27","author":[{"given":"Sixian","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Oncology, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology  Wuhan 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