{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T15:16:21Z","timestamp":1774538181995,"version":"3.50.1"},"reference-count":42,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T00:00:00Z","timestamp":1774483200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Science and Technology Support Programs of Sichuan Province","award":["2025ZNSFSC1901"],"award-info":[{"award-number":["2025ZNSFSC1901"]}]},{"name":"Science and Technology Support Programs of Sichuan Province","award":["2026NSFSC1950"],"award-info":[{"award-number":["2026NSFSC1950"]}]},{"name":"Postdoctoral Research Funds of West China Hospital, Sichuan University","award":["2025HXBH050"],"award-info":[{"award-number":["2025HXBH050"]}]},{"name":"Postdoctoral Research Funds of West China Hospital, Sichuan University","award":["2025HXBH103"],"award-info":[{"award-number":["2025HXBH103"]}]},{"name":"Peak Discipline Operation Fund of West China Hospital","award":["GFYX25004"],"award-info":[{"award-number":["GFYX25004"]}]},{"name":"State-Owned Assets Supervision and Administration Commission Program C","award":["GZC20251423"],"award-info":[{"award-number":["GZC20251423"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Current Oncology"],"abstract":"<jats:p>WD repeat and HMG-box DNA-binding protein 1 (WDHD1) has been identified as a crucial oncogene in various tumors, but its role in pancreatic cancer remains unexplored. This study investigated the mechanisms by which WDHD1 contributes to pancreatic cancer progression. Differential analysis of the Cancer Genome Atlas (TCGA) pancreatic cancer samples identified abnormally expressed genes. Cellular assays, including cell proliferation, flow cytometry, and apoptosis assays, demonstrated WDHD1\u2019s oncogenic role. WDHD1 expression was significantly elevated in pancreatic cancer cells and tissues compared to normal counterparts. Knockdown of WDHD1 inhibited cell proliferation, induced apoptosis, and caused G1-phase cell-cycle arrest. In vivo xenograft models further validated that WDHD1 knockdown suppressed the growth of pancreatic cancer cells. Mechanistically, WDHD1 knockdown resulted in significant reductions in CDK4 and cyclin D1 protein levels, whereas WDHD1 overexpression produced the opposite effects. Additionally, E2F1 overexpression increased the expression of WDHD1 at both mRNA and protein levels. Rescue experiments revealed that WDHD1 knockdown could reverse the E2F1-induced upregulation of CDK4 and cyclin D1 protein levels. In conclusion, E2F1 promotes pancreatic cancer cell proliferation and cell-cycle progression by upregulating WDHD1, which in turn enhances the expression of the CDK4\u2013cyclin D1 complex.<\/jats:p>","DOI":"10.3390\/curroncol33040186","type":"journal-article","created":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T13:50:15Z","timestamp":1774533015000},"page":"186","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["E2F1-Driven WDHD1 Transcription Enhances Cell-Cycle Progression and Promotes Pancreatic Cancer Progression"],"prefix":"10.3390","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-9430-6482","authenticated-orcid":false,"given":"Xiaojuan","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Abdominal Oncology, West China Hospital, Sichuan University, Chengdu 610041, China"},{"name":"Laboratory of Hepatic AI Translation, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhiwei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Abdominal Oncology, West China Hospital, Sichuan University, Chengdu 610041, China"},{"name":"Key Laboratory of Cancer Prevention and Intervention, Department of Colorectal Surgery and Oncology, Ministry of Education, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 322000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuangjuan","family":"Lv","sequence":"additional","affiliation":[{"name":"Laboratory of Hepatic AI Translation, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Buzhe","family":"Zhang","sequence":"additional","affiliation":[{"name":"Laboratory of Hepatic AI Translation, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xue","family":"Tao","sequence":"additional","affiliation":[{"name":"Laboratory of Hepatic AI Translation, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Abdominal Oncology, West China Hospital, Sichuan University, Chengdu 610041, China"},{"name":"Intervention Center, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Chengdu 610041, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qing","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Abdominal Oncology, West China Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,26]]},"reference":[{"key":"ref_1","unstructured":"GBD 2017 Pancreatic Cancer Collaborators (2019). 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