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(Landmark Ed)"],"abstract":"<jats:p>Background: Pancreatic cancer ranks among the leading causes of cancer-related death worldwide, and novel therapeutic strategies are urgently needed for advanced or metastatic disease states. Notably, targeted therapy remains a particularly promising approach. The transcription factor FOS-like antigen 1 (FOSL1) is overexpressed in refractory pancreatic cancers and drives tumor progression, correlating with unfavorable clinical outcomes. Thus, this study aimed to investigate the molecular mechanisms through which FOSL1 and proliferating cell nuclear antigen (PCNA) promote pancreatic cancer progression by regulating DNA repair, invasion, and migration. Methods: We evaluated the role of FOSL1 in pancreatic cancer cell proliferation, DNA repair, stemness, invasion, and migration, and identified downstream targets and pathways through transcriptomic analysis. Mechanistically, we validated the FOSL1\u2013PCNA interaction, FOSL1 binding to the PCNA promoter, and the role of FOSL1 in regulating PCNAubiquitination. Finally, we assessed whether FOSL1 functions through PCNA and explored the effects of combined FOSL1 knockdown and PCNA inhibition. Results: FOSL1 depletion altered cell proliferation, steady-state DNA damage, stemness-associated markers, invasion, and migration. PCNA overexpression partially rescued the reduction in colony formation caused by FOSL1 knockdown. Mechanistically, FOSL1 binds the PCNA promoter, and FOSL1 knockdown reduced PCNA mRNA expression. Moreover, chromatin immunoprecipitation\u2013quantitative PCR (ChIP\u2013qPCR) showed that FOSL1 occupies the PCNA promoter region. Conversely, PCNA knockdown suppressed pancreatic cancer cell proliferation and impaired the expression of genes involved in DNA repair, stemness, and epithelial-mesenchymal transition (EMT)-mediated invasion and migration. Conclusion: Our findings indicate that FOSL1 promotes pancreatic cancer progression, at least in part by upregulating PCNA expression. We hypothesize that combined inhibition of FOSL1 and PCNA may represent a therapeutic strategy for advanced pancreatic cancer.<\/jats:p>","DOI":"10.31083\/fbl52523","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T16:21:51Z","timestamp":1790698911000},"source":"Crossref","is-referenced-by-count":0,"title":["FOS-Like Antigen 1 Regulates Proliferating Cell Nuclear Antigen Expression and Pancreatic Cancer Cell Proliferation and Migration"],"prefix":"10.31083","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-5880-6199","authenticated-orcid":true,"given":"Xueyan","family":"Zhang","sequence":"first","affiliation":[{"name":"Key Laboratory of Preclinical Study for New Drugs of Gansu Province, Institute of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Lanzhou University, 730000 Lanzhou, Gansu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-0646-3098","authenticated-orcid":true,"given":"Yu","family":"An","sequence":"additional","affiliation":[{"name":"Key Laboratory of Preclinical Study for New Drugs of Gansu Province, Institute of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Lanzhou University, 730000 Lanzhou, Gansu, China"},{"name":"The First School of Clinical Medicine, Lanzhou University, 730000 Lanzhou, Gansu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-0660-909X","authenticated-orcid":true,"given":"Jipin","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Preclinical Study for New Drugs of Gansu Province, Institute of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Lanzhou University, 730000 Lanzhou, Gansu, China"},{"name":"The Second Hospital & Clinical Medical School, Lanzhou University, 730030 Lanzhou, Gansu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-8598-7955","authenticated-orcid":true,"given":"Yali","family":"Chen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Preclinical Study for New Drugs of Gansu Province, Institute of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Lanzhou University, 730000 Lanzhou, Gansu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-5464-2197","authenticated-orcid":true,"given":"Tingyu","family":"Zeng","sequence":"additional","affiliation":[{"name":"Key Laboratory of Preclinical Study for New Drugs of Gansu Province, Institute of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Lanzhou University, 730000 Lanzhou, Gansu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0086-260X","authenticated-orcid":true,"given":"Shuping","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Preclinical Study for New Drugs of Gansu Province, Institute of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Lanzhou University, 730000 Lanzhou, Gansu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"16242","published-online":{"date-parts":[[2026,9,17]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","unstructured":"Schwartz SM. 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