{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T15:49:32Z","timestamp":1790092172061,"version":"4.0.1"},"reference-count":27,"publisher":"Wiley","issue":"18","license":[{"start":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T00:00:00Z","timestamp":1758499200000},"content-version":"vor","delay-in-days":21,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007847","name":"Natural Science Foundation of Jilin Province","doi-asserted-by":"publisher","award":["YDZJ202301ZYTS455"],"award-info":[{"award-number":["YDZJ202301ZYTS455"]}],"id":[{"id":"10.13039\/100007847","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005047","name":"Natural Science Foundation of Liaoning Province","doi-asserted-by":"publisher","award":["2024\u2010BS\u2010177"],"award-info":[{"award-number":["2024\u2010BS\u2010177"]}],"id":[{"id":"10.13039\/501100005047","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":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Hepatocellular carcinoma (HCC) is a common and deadly type of liver cancer with limited treatment options and a considerable issue with chemoresistance. This study investigates the role of the cytoskeleton\u2010associated protein G (CAPG) gene in HCC and explores its expression, clinical relevance, as well as the molecular mechanisms on doxorubicin (Dox) resistance. Employing bioinformatics, immunohistochemistry, cell\u2010based assays and animal models, we systematically explored CAPG's function in HCC. Our results demonstrated that CAPG was markedly upregulated in HCC tissues and cell lines compared to normal controls (***\n                    <jats:italic>p<\/jats:italic>\n                    &lt;\u20090.001). High CAPG expression was associated with poor overall survival (HR\u2009=\u20091.98,\n                    <jats:italic>p<\/jats:italic>\n                    &lt;\u20090.001) and unfavourable clinicopathological parameters, indicating its potential as a prognostic biomarker. Functional experiments indicated that CAPG knockdown significantly reduced viability and proliferation in Dox\u2010resistant HCC cells (***\n                    <jats:italic>p<\/jats:italic>\n                    &lt;\u20090.01). Conversely, overexpression promoted resistance. Mechanistically, CAPG appears to modulate ferroptosis via the TGFB1\/Smad2\/NRF2 signalling pathway, as supported by GSEA analysis and subsequent molecular assays. In\u00a0vivo, CAPG knockdown in combination with Dox treatment significantly inhibited tumour growth in nude mouse models (***\n                    <jats:italic>p<\/jats:italic>\n                    &lt;\u20090.01). These findings suggest that CAPG is a pivotal regulator of HCC progression and chemoresistance, offering a promising prognostic biomarker and combinatorial therapeutic target to overcome Dox resistance in clinical settings.\n                  <\/jats:p>","DOI":"10.1111\/jcmm.70847","type":"journal-article","created":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T16:40:07Z","timestamp":1758559207000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["<scp>CAPG<\/scp>\n                    Regulates Doxorubicin Resistance in Hepatocellular Carcinoma Cells via\n                    <scp>TGFB1<\/scp>\n                    \/Smad\/Nrf2 Signalling Pathway"],"prefix":"10.1111","volume":"29","author":[{"given":"Yue","family":"Shang","sequence":"first","affiliation":[{"name":"Department of Pharmacy The Second Hospital of Dalian Medical University  Dalian Liaoning China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, School of Basic Medical Sciences Jilin Medical University  Jilin Jilin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-6996-4595","authenticated-orcid":false,"given":"Tingting","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy The Second Hospital of Dalian Medical University  Dalian Liaoning China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,9,22]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.17998\/jlc.2024.06.26"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers16122183"},{"key":"e_1_2_11_4_1","first-page":"12","article-title":"Molecular Bases of Drug Resistance in Hepatocellular Carcinoma","volume":"12","author":"Marin J. J. G.","year":"2020","journal-title":"Cancers (Basel)"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drup.2024.101084"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.2147\/JHC.S469449"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2024.103137"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2024.150200"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers16081540"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drup.2024.101052"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41420-023-01767-6"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-023-01806-x"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcp.2023.101919"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-023-04973-1"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12957-022-02808-7"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2021.02.038"},{"key":"e_1_2_11_17_1","first-page":"186","article-title":"The Association Between Gelsolin\u2010Like Actin\u2010Capping Protein (CapG) Overexpression and Bladder Cancer Prognosis","volume":"18","author":"Bahrami S.","year":"2020","journal-title":"Urology Journal"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11010-024-04992-4"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humimm.2022.10.001"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10616-023-00584-0"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-024-06464-5"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2020.112453"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2407-14-577"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.22523"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.21873\/anticanres.12680"},{"key":"e_1_2_11_26_1","first-page":"14","article-title":"Ferroptosis and Nrf2 Signaling in Head and Neck Cancer: Resistance Mechanisms and Therapeutic Prospects","volume":"14","author":"Lee J.","year":"2025","journal-title":"Antioxidants (Basel)"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers17162714"},{"key":"e_1_2_11_28_1","first-page":"1","article-title":"NRF2 as a Ferroptosis Gatekeeper in Colorectal Cancer: Implications for Therapy","author":"Abdelgawwad El\u2010Sehrawy A. A. M.","year":"2025","journal-title":"Naunyn\u2010Schmiedeberg's Archives of Pharmacology"}],"container-title":["Journal of Cellular and Molecular Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jcmm.70847","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T09:06:34Z","timestamp":1764666394000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jcmm.70847"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9]]},"references-count":27,"journal-issue":{"issue":"18","published-print":{"date-parts":[[2025,9]]}},"alternative-id":["10.1111\/jcmm.70847"],"URL":"https:\/\/doi.org\/10.1111\/jcmm.70847","archive":["Portico"],"relation":{},"ISSN":["1582-1838","1582-4934"],"issn-type":[{"value":"1582-1838","type":"print"},{"value":"1582-4934","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9]]},"assertion":[{"value":"2024-09-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-06","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-22","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70847"}}