{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T13:07:24Z","timestamp":1789477644189,"version":"build-2803163510"},"reference-count":42,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"vor","delay-in-days":257,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Zhanjiang City Science and Technology Plan Project","award":["2022A703\u20133"],"award-info":[{"award-number":["2022A703\u20133"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Cervical cancer remains a leading cause of cancer-related deaths among women worldwide. Targeting ferroptosis, a regulated form of cell death driven by lipid peroxidation, has emerged as a promising therapeutic strategy. This study aimed to elucidate the mechanisms by which cervical cancer cells acquire resistance to ferroptosis. AGRN expression and its prognostic significance were analyzed in cervical cancer using TCGA and GTEx data. In vitro, AGRN levels were measured in HeLa, CaSki, and Ect1\/E6E7 cells via qRT-PCR. mRNA and protein expression levels of AGRN, beta-catenin, and ferroptosis-related markers were evaluated by qRT-PCR and western blot (WB). Cell viability, RSL3 sensitivity (IC50), and lipid ROS were assessed via CCK-8 assay and flow cytometry. In a xenograft model, RSL3\u2019s effect on tumor growth was examined. Immunohistochemistry (IHC) and molecular analyses (qRT-PCR, WB, and flow cytometry) were performed on tumor tissues to evaluate AGRN, beta-catenin, Ki-67, ferroptosis-related genes, and lipid ROS. It is found through research that, AGRN was significantly upregulated in cervical cancer tissues and cell lines. Its overexpression activated Wnt\/beta-catenin signaling, resulting in elevated GPX4 and SLC7A11 levels and reduced CHAC1 and PTGS2 expression levels. These alterations decreased lipid ROS accumulation and enhanced resistance to RSL3-induced ferroptosis, an effect further confirmed in xenograft models. In short, In short, AGRN promotes ferroptosis resistance in cervical cancer by activating the Wnt\/beta-catenin signaling pathway and upregulating GPX4 expression. Targeting the AGRN\u2013Wnt\/beta-catenin\u2013GPX4 axis may represent a novel therapeutic approach for cervical cancer.<\/jats:p>","DOI":"10.1093\/bfgp\/elag010","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T11:15:03Z","timestamp":1786965303000},"source":"Crossref","is-referenced-by-count":0,"title":["AGRN activates GPX4\n                    <i>via<\/i>\n                    the Wnt\/beta-catenin signaling pathway to suppress ferroptosis in cervical cancer cells"],"prefix":"10.1093","volume":"25","author":[{"given":"Aizhen","family":"Fu","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Affiliated Hospital of Guangdong Medical University , No. 57 Renmin Avenue South, Xiashan District, Zhanjiang, Guangdong 524000 ,","place":["China"]},{"name":"Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Guangdong Medical University , No. 12 Minyou Road, Xiashan District, Zhanjiang, Guangdong 524000 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayi","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Oncology, Zhujiang Hospital, Southern Medical University , No. 253 Industrial Avenue, Haizhu District, Guangzhou, Guangdong 510282 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruitao","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Affiliated Hospital of Guangdong Medical University , No. 57 Renmin Avenue South, Xiashan District, Zhanjiang, Guangdong 524000 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinxin","family":"Zou","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Affiliated Hospital of Guangdong Medical University , No. 57 Renmin Avenue South, Xiashan District, Zhanjiang, Guangdong 524000 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongfeng","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Affiliated Hospital of Guangdong Medical University , No. 57 Renmin Avenue South, Xiashan District, Zhanjiang, Guangdong 524000 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengping","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Affiliated Hospital of Guangdong Medical University , No. 57 Renmin Avenue South, Xiashan District, Zhanjiang, Guangdong 524000 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Affiliated Hospital of Guangdong Medical University , No. 57 Renmin Avenue South, Xiashan District, Zhanjiang, Guangdong 524000 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Affiliated Hospital of Guangdong Medical University , No. 57 Renmin Avenue South, Xiashan District, Zhanjiang, Guangdong 524000 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Affiliated Hospital of Guangdong Medical University , No. 57 Renmin Avenue South, Xiashan District, Zhanjiang, Guangdong 524000 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renhe","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Guangdong Medical University , No. 12 Minyou Road, Xiashan District, Zhanjiang, Guangdong 524000 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