{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T02:52:34Z","timestamp":1788317554543,"version":"build-2803163510"},"reference-count":30,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T00:00:00Z","timestamp":1771891200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T00:00:00Z","timestamp":1774569600000},"content-version":"vor","delay-in-days":31,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"the National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82220108019"],"award-info":[{"award-number":["82220108019"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"DOI":"10.1038\/s41598-026-37710-9","type":"journal-article","created":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T20:46:46Z","timestamp":1771966006000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["AT-101 inhibits the proliferation and invasion of tongue squamous carcinoma cells by targeting the miR-21-5p\/FDX1 axis"],"prefix":"10.1038","volume":"16","author":[{"given":"Shuai","family":"Fu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing-ying","family":"Cui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-yu","family":"Tuo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Ji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,24]]},"reference":[{"key":"37710_CR1","doi-asserted-by":"publisher","first-page":"401","DOI":"10.3322\/caac.21293","volume":"65","author":"AC Chi","year":"2015","unstructured":"Chi, A. C., Day, T. A. & Neville, B. W. Oral cavity and oropharyngeal squamous cell carcinoma\u2013an update. CA Cancer J. Clin. 65, 401\u2013421. https:\/\/doi.org\/10.3322\/caac.21293 (2015).","journal-title":"CA Cancer J. Clin."},{"key":"37710_CR2","doi-asserted-by":"publisher","first-page":"1641","DOI":"10.1080\/15384101.2020.1762048","volume":"19","author":"H Feng","year":"2020","unstructured":"Feng, H., Zhang, X. Q., Lai, W. L. & Wang, J. Long non-coding RNA SLC16A1-AS1: its multiple tumorigenesis features and regulatory role in cell cycle in oral squamous cell carcinoma. Cell. Cycle. 19, 1641\u20131653. https:\/\/doi.org\/10.1080\/15384101.2020.1762048 (2020).","journal-title":"Cell. Cycle"},{"key":"37710_CR3","doi-asserted-by":"publisher","first-page":"113608","DOI":"10.1016\/j.ejmech.2021.113608","volume":"222","author":"Z. Z. Li","year":"2021","unstructured":"Li, Z. Z. et al. Development of photocontrolled BRD4 PROTACs for tongue squamous cell carcinoma (TSCC). Eur. J. Med. Chem. 222, 113608 (2021).","journal-title":"Eur. J. Med. Chem."},{"key":"37710_CR4","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1016\/j.jgg.2020.07.001","volume":"47","author":"SH Wang","year":"2020","unstructured":"Wang, S. H. et al. Whole-exome sequencing reveals genetic underpinnings of salivary adenoid cystic carcinoma in the Chinese population. J. Genet. Genomics. 47, 397\u2013401. https:\/\/doi.org\/10.1016\/j.jgg.2020.07.001 (2020).","journal-title":"J. Genet. Genomics"},{"key":"37710_CR5","doi-asserted-by":"publisher","first-page":"761","DOI":"10.1177\/01945998221098011","volume":"168","author":"KO Stepan","year":"2023","unstructured":"Stepan, K. O. et al. Changing epidemiology of oral cavity cancer in the united States. Otolaryng Head Neck. 168, 761\u2013768 (2023). doi:Artn 0194599822109801110.1177\/01945998221098011.","journal-title":"Otolaryng Head Neck"},{"key":"37710_CR6","doi-asserted-by":"publisher","first-page":"1418","DOI":"10.3892\/ijmm.2018.3742","volume":"42","author":"XG Liu","year":"2018","unstructured":"Liu, X. G. et al. Sox2 promotes tumor aggressiveness and epithelial-mesenchymal transition in tongue squamous cell carcinoma. Int. J. Mol. Med. 42, 1418\u20131426. https:\/\/doi.org\/10.3892\/ijmm.2018.3742 (2018).","journal-title":"Int. J. Mol. Med."},{"key":"37710_CR7","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1038\/s41368-024-00343-7","volume":"17","author":"M. Hao","year":"2025","unstructured":"Hao, M. et al. Tongue squamous cell carcinoma-targeting Au-HN-1 nanosystem for CT imaging and photothermal therapy. Int. J. Oral Sci. 17, 9 (2025).","journal-title":"Int. J. Oral Sci."},{"key":"37710_CR8","doi-asserted-by":"publisher","first-page":"217230","DOI":"10.1016\/j.canlet.2024.217230","volume":"604","author":"S. L. Xie","year":"2024","unstructured":"Xie, S. L. et al. A tumor-promotional molecular axis CircMAPKBP1\/miR-17-3p\/TGF\u03b22 activates autophagy pathway to drive tongue squamous cell carcinoma cisplatin chemoresistance. Cancer Lett. 604, 217230 (2024).","journal-title":"Cancer Lett."},{"key":"37710_CR9","doi-asserted-by":"publisher","first-page":"3924","DOI":"10.1016\/j.ejca.2013.07.149","volume":"49","author":"H Wang","year":"2013","unstructured":"Wang, H. et al. miR-133a represses tumour growth and metastasis in colorectal cancer by targeting LIM and SH3 protein 1 and inhibiting the MAPK pathway. Eur. J. Cancer. 49, 3924\u20133935. https:\/\/doi.org\/10.1016\/j.ejca.2013.07.149 (2013).","journal-title":"Eur. J. Cancer"},{"key":"37710_CR10","doi-asserted-by":"publisher","first-page":"576","DOI":"10.1038\/s41419-021-03803-8","volume":"12","author":"Q. L. He","year":"2021","unstructured":"He, Q. L. et al. Cancer-secreted exosomal miR-21-5p induces angiogenesis and vascular permeability by targeting KRIT1. Cell. Death Dis. 12, 576 (2021).","journal-title":"Cell. Death Dis."},{"key":"37710_CR11","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1186\/s13075-020-2145-y","volume":"22","author":"S. X. Ma","year":"2020","unstructured":"Ma, S. X. et al. MiR-21-5p regulates extracellular matrix degradation and angiogenesis in TMJOA by targeting Spry1. Arthritis Res. Ther. 22, 99 (2020).","journal-title":"Arthritis Res. Ther."},{"key":"37710_CR12","doi-asserted-by":"publisher","first-page":"322","DOI":"10.1007\/s10142-023-01246-2","volume":"23","author":"L. Zhang","year":"2023","unstructured":"Zhang, L. & Liu, J. M. miR-21-5p inhibits the growth of brain glioma cells through regulating the glycolysis mediated by PFKFB2. Funct. Integr. Genomic. 23, 322 (2023).","journal-title":"Funct. Integr. Genomic"},{"key":"37710_CR13","doi-asserted-by":"publisher","first-page":"11775","DOI":"10.1073\/pnas.1004250107","volume":"107","author":"AD Sheftel","year":"2010","unstructured":"Sheftel, A. D. et al. Humans possess two mitochondrial ferredoxins, Fdx1 and Fdx2, with distinct roles in steroidogenesis, heme, and Fe\/S cluster biosynthesis. P Natl. Acad. Sci. USA. 107, 11775\u201311780. https:\/\/doi.org\/10.1073\/pnas.1004250107 (2010).","journal-title":"P Natl. Acad. Sci. USA"},{"key":"37710_CR14","doi-asserted-by":"publisher","first-page":"103302","DOI":"10.1016\/j.redox.2024.103302","volume":"75","author":"B. Sun","year":"2024","unstructured":"Sun, B. et al. FDX1 downregulation activates mitophagy and the PI3K\/AKT signaling pathway to promote hepatocellular carcinoma progression by inducing ROS production. Redox Biol. 75, 103302 (2024).","journal-title":"Redox Biol."},{"key":"37710_CR15","doi-asserted-by":"publisher","first-page":"173","DOI":"10.3390\/cells12010173","volume":"12","author":"M. Y. Xie","year":"2023","unstructured":"Xie, M. Y. et al. Cuproptosis-Related MiR-21-5p\/FDX1 Axis in Clear Cell Renal Cell Carcinoma and Its Potential Impact on Tumor Microenvironment. Cells-Basel 12, 173 (2023).","journal-title":"Cells-Basel"},{"key":"37710_CR16","doi-asserted-by":"publisher","first-page":"1269","DOI":"10.3389\/fphar.2018.01269","volume":"9","author":"M. Benvenuto","year":"2018","unstructured":"Benvenuto, M. et al. Effect of the BH3 Mimetic Polyphenol (-)-Gossypol (AT-101) on the and Growth of Malignant Mesothelioma. Front. Pharmacol. 9, 1269 (2018).","journal-title":"Front. Pharmacol."},{"key":"37710_CR17","doi-asserted-by":"publisher","first-page":"227","DOI":"10.2147\/Ijn.S341824","volume":"17","author":"H Liu","year":"2022","unstructured":"Liu, H. et al. Cyclic RGD-Decorated liposomal gossypol AT-101 targeting for enhanced antitumor effect. Int. J. Nanomed. 17, 227\u2013244. https:\/\/doi.org\/10.2147\/Ijn.S341824 (2022).","journal-title":"Int. J. Nanomed."},{"key":"37710_CR18","doi-asserted-by":"publisher","first-page":"613","DOI":"10.1038\/clpt.1986.108","volume":"39","author":"DF Wu","year":"1986","unstructured":"Wu, D. F., Yu, Y. W., Tang, Z. M. & Wang, M. Z. Pharmacokinetics of (+\/-)-, (+)-, and (-)-gossypol in humans and dogs. Clin. Pharmacol. Ther. 39, 613\u2013618. https:\/\/doi.org\/10.1038\/clpt.1986.108 (1986).","journal-title":"Clin. Pharmacol. Ther."},{"key":"37710_CR19","doi-asserted-by":"publisher","first-page":"144","DOI":"10.3390\/ph15020144","volume":"15","author":"O. Renner","year":"2022","unstructured":"Renner, O. et al. Systematic review of Gossypol\/AT-101 in cancer clinical trials. Pharmaceuticals-Base 15, 144 (2022).","journal-title":"Pharmaceuticals-Base"},{"key":"37710_CR20","doi-asserted-by":"publisher","first-page":"3543","DOI":"10.3892\/etm.2019.7970","volume":"18","author":"CF Liu","year":"2019","unstructured":"Liu, C. F. et al. MicroRNA-21-5p targeting PDCD4 suppresses apoptosis via regulating the PI3K\/AKT\/FOXO1 signaling pathway in tongue squamous cell carcinoma. Exp. Ther. Med. 18, 3543\u20133551. https:\/\/doi.org\/10.3892\/etm.2019.7970 (2019).","journal-title":"Exp. Ther. Med."},{"key":"37710_CR21","doi-asserted-by":"publisher","first-page":"300","DOI":"10.1186\/s12935-024-03485-0","volume":"24","author":"Z. Li","year":"2024","unstructured":"Li, Z. et al. Capsaicin combined with cisplatin inhibits TGF-\u03b21-induced EMT and TSCC cells migration via the Claudin-1\/PI3K\/AKT\/mTOR signaling pathway. Cancer Cell. Int. 24, 300 (2024).","journal-title":"Cancer Cell. Int."},{"key":"37710_CR22","doi-asserted-by":"crossref","unstructured":"Jiang, R. et al. (ed , L.) MiR-21-5p induces pyroptosis in colorectal cancer TGFBI. Front. Oncol. 10 610545 (2021).","DOI":"10.3389\/fonc.2020.610545"},{"key":"37710_CR23","doi-asserted-by":"publisher","unstructured":"Hu, Z. Q. et al. miR-21-5p inhibits ferroptosis in hepatocellular carcinoma cells by regulating the AKT\/mTOR signaling pathway through MELK. J Immunol. Res (2023). https:\/\/doi.org\/10.1155\/2023\/8929525 (2023).","DOI":"10.1155\/2023\/8929525"},{"key":"37710_CR24","doi-asserted-by":"publisher","first-page":"382","DOI":"10.1186\/s12967-023-04190-8","volume":"21","author":"K. Li","year":"2023","unstructured":"Li, K. et al. HNRNPA2B1-mediated m A modification of lncRNA MEG3 facilitates tumorigenesis and metastasis of non-small cell lung cancer by regulating miR-21-5p\/PTEN axis. J. Transl Med. 21, 382 (2023). https:\/\/doi.org\/10.1186\/s12967-023-04190-8","journal-title":"J. Transl Med."},{"key":"37710_CR25","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1038\/s41589-022-01159-4","volume":"19","author":"V Schulz","year":"2023","unstructured":"Schulz, V. et al. Functional spectrum and specificity of mitochondrial ferredoxins FDX1 and FDX2. Nat. Chem. Biol. 19, 206\u2013. https:\/\/doi.org\/10.1038\/s41589-022-01159-4 (2023).","journal-title":"Nat. Chem. Biol."},{"key":"37710_CR26","doi-asserted-by":"publisher","unstructured":"Qi, R. Q. et al. Elabela alleviates Cuproptosis and vascular calcification in vitaminD3-overloaded mice via regulation of the PPAR-\u03b3 \/FDX1 signaling. Mol. Med. 30 https:\/\/doi.org\/10.1186\/s10020-024-00997-3 (2024). doi:ARTN.","DOI":"10.1186\/s10020-024-00997-3"},{"key":"37710_CR27","doi-asserted-by":"publisher","first-page":"477","DOI":"10.3390\/cancers15020477","volume":"15","author":"S. Ailawadhi","year":"2023","unstructured":"Ailawadhi, S. et al. AT-101 Enhances the Antitumor Activity of Lenalidomide in Patients with Multiple Myeloma. Cancers 15, 477 (2023). https:\/\/doi.org\/10.3390\/cancers15020477","journal-title":"Cancers"},{"key":"37710_CR28","doi-asserted-by":"publisher","first-page":"2177","DOI":"10.1038\/s41418-022-01007-x","volume":"29","author":"Y Yang","year":"2022","unstructured":"Yang, Y. et al. Targeting the miR-34a\/LRPPRC\/MDR1 axis collapse the chemoresistance in P53 inactive colorectal cancer. Cell. Death Differ. 29, 2177\u20132189. https:\/\/doi.org\/10.1038\/s41418-022-01007-x (2022).","journal-title":"Cell. Death Differ."},{"key":"37710_CR29","doi-asserted-by":"publisher","unstructured":"Wang, S. et al. Near-Infrared activatable copper nanoplatforms synergize with the 5-Azacytidine prodrug to potentiate Cuproptosis. Angew Chem. Int. Edit. 63 https:\/\/doi.org\/10.1002\/anie.202411609 (2024).","DOI":"10.1002\/anie.202411609"},{"key":"37710_CR30","doi-asserted-by":"publisher","first-page":"e18655","DOI":"10.1016\/j.heliyon.2023.e18655","volume":"9","author":"G Chen","year":"2023","unstructured":"Chen, G., Zhang, J., Teng, W., Luo, Y. & Ji, X. FDX1 inhibits thyroid cancer malignant progression by inducing cuprotosis. Heliyon 9, e18655. https:\/\/doi.org\/10.1016\/j.heliyon.2023.e18655 (2023).","journal-title":"Heliyon"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-37710-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-37710-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-37710-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T10:19:07Z","timestamp":1774606747000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-37710-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,24]]},"references-count":30,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["37710"],"URL":"https:\/\/doi.org\/10.1038\/s41598-026-37710-9","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,24]]},"assertion":[{"value":"29 March 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 January 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 February 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"This study was approved by the Ethics Committee of the Stomatological Hospital of Kunming Medical University(#KYKQ2021MEC063, Kunming, Yunnan, China), conducted in accordance with the Declaration of Helsinki, and written informed consent was obtained from each patient.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}],"article-number":"10361"}}