{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T17:51:21Z","timestamp":1792173081177,"version":"4.4.0"},"reference-count":23,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:00:00Z","timestamp":1790294400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:00:00Z","timestamp":1790294400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biochem &amp;amp; Molecular Tox"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    This study aimed to investigate the role and molecular mechanisms of origin recognition complex 1 (ORC1) in Cisplatin resistance and tumor stemness in non\u2010small cell lung cancer (NSCLC), and to evaluate its potential as a target for reversing chemotherapy resistance. ORC1 expression and its clinical significance in NSCLC were analyzed using TCGA and GTEx databases. ORC1\u2010knockdown NSCLC cell lines and Cisplatin\u2010resistant A549 DDP cells were established. Colony formation, Transwell, tumor sphere formation, and flow cytometry assays were performed to assess proliferation, invasion, stemness, and drug resistance phenotypes. A subcutaneous xenograft model in nude mice was used to evaluate the in vivo antitumor efficacy of lentivirus\u2010mediated ORC1 knockdown combined with Cisplatin. Protein expression levels of stemness markers (LGR5, NANOG, CD44), the resistance\u2010associated protein P\u2010gp, and EMT\u2010related proteins were detected by Western blotting. ORC1 was significantly overexpressed in NSCLC tissues and resistant cells, and its expression positively correlated with poor prognosis and tumor stemness markers. ORC1 knockdown markedly inhibited proliferation, invasion, EMT, and sphere\u2010forming capacity, and downregulated stemness\u2010associated proteins. In A549 DDP cells, ORC1 knockdown reduced the Cisplatin IC\n                    <jats:sub>50<\/jats:sub>\n                    , restored chemosensitivity, downregulated MDR1\/P\u2010gp, and enhanced Cisplatin\u2010induced apoptosis. In vivo, ORC1 knockdown combined with Cisplatin significantly suppressed resistant tumor growth, reduced the proportion of CD133\n                    <jats:sup>+<\/jats:sup>\n                    CD44\n                    <jats:sup>+<\/jats:sup>\n                    cancer stem cells, and promoted apoptosis. ORC1 mediated Cisplatin resistance in NSCLC by regulating tumor stemness and EMT. Targeted silencing of ORC1 effectively reversed resistance both in vitro and in vivo, representing a potential molecular target for overcoming Cisplatin resistance in NSCLC.\n                  <\/jats:p>","DOI":"10.1002\/jbt.71078","type":"journal-article","created":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T10:01:39Z","timestamp":1790330499000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mechanism of ORC1 Regulating Cancer Stemness and Cisplatin Resistance in Non\u2010Small Cell Lung Cancer"],"prefix":"10.1002","volume":"40","author":[{"given":"Jianhui","family":"Sheng","sequence":"first","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine Yantaishan Hospital Yantai Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-8332-6378","authenticated-orcid":false,"given":"Yingjian","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery Yantai Yuhuangding Hospital Yantai Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,25]]},"reference":[{"key":"e_1_2_10_2_1","first-page":"2022","article-title":"Current Status of Immunotherapy for Non\u2010Small Cell Lung Cancer","volume":"13","author":"Yang T.","year":"2022","journal-title":"Frontiers in 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