{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T00:52:45Z","timestamp":1781484765595,"version":"3.54.1"},"reference-count":72,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T00:00:00Z","timestamp":1777248000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T00:00:00Z","timestamp":1781481600000},"content-version":"vor","delay-in-days":49,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/501100003399","name":"Shanghai Science and Technology Committee","doi-asserted-by":"crossref","award":["19QA1407700"],"award-info":[{"award-number":["19QA1407700"]}],"id":[{"id":"10.13039\/501100003399","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82373269"],"award-info":[{"award-number":["82373269"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"2020 Special Research Project of Family Planning","award":["20JSZ12"],"award-info":[{"award-number":["20JSZ12"]}]},{"name":"Shanghai Fourth's People's Hospital","award":["SY-XKZT-2025-1002, Sykyqd11701"],"award-info":[{"award-number":["SY-XKZT-2025-1002, Sykyqd11701"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Transl Med"],"DOI":"10.1186\/s12967-026-08182-2","type":"journal-article","created":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T16:13:11Z","timestamp":1777306391000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pharmacological targeting of SF3a1-MDM4 splicing vulnerability in ovarian cancer with rifaximin and antisense oligonucleotide"],"prefix":"10.1186","volume":"24","author":[{"given":"Xueqian","family":"Shuai","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaoqi","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiale","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongping","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9276-7086","authenticated-orcid":false,"given":"Shupeng","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,27]]},"reference":[{"key":"8182_CR1","unstructured":"The website of the National Cancer Institute. https:\/\/www.cancer.gov. Accessed 20 June 2025."},{"key":"8182_CR2","doi-asserted-by":"publisher","first-page":"1963","DOI":"10.1002\/cncr.32004","volume":"125","author":"RC Bast Jr","year":"2019","unstructured":"Bast RC Jr., Matulonis UA, Sood AK, Ahmed AA, Amobi AE, Balkwill FR, et al. Critical questions in ovarian cancer research and treatment: Report of an American Association for Cancer Research Special Conference. Cancer. 2019;125:1963\u201372.","journal-title":"Cancer"},{"key":"8182_CR3","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1186\/s12943-024-01967-3","volume":"23","author":"L Wang","year":"2024","unstructured":"Wang L, Wang X, Zhu X, Zhong L, Jiang Q, Wang Y, et al. Drug resistance in ovarian cancer: from mechanism to clinical trial. Mol Cancer. 2024;23:66.","journal-title":"Mol Cancer"},{"key":"8182_CR4","first-page":"10456","volume":"43","author":"A Crisci","year":"2015","unstructured":"Crisci A, Raleff F, Bagdiul I, Raabe M, Urlaub H, Rain JC, et al. Mammalian splicing factor SF1 interacts with SURP domains of U2 snRNP-associated proteins. Nucleic Acids Res. 2015;43:10456\u201373.","journal-title":"Nucleic Acids Res"},{"key":"8182_CR5","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1016\/S1097-2765(03)00270-3","volume":"12","author":"MS Jurica","year":"2003","unstructured":"Jurica MS, Moore MJ. Pre-mRNA splicing: awash in a sea of proteins. Mol Cell. 2003;12:5\u201314.","journal-title":"Mol Cell"},{"key":"8182_CR6","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1186\/s12964-024-01880-8","volume":"22","author":"L Wei","year":"2024","unstructured":"Wei L, Li Y, Chen J, Wang Y, Wu J, Yang H, et al. Alternative splicing in ovarian cancer. Cell Commun Signal. 2024;22:507.","journal-title":"Cell Commun Signal"},{"key":"8182_CR7","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1038\/s41419-022-04630-1","volume":"13","author":"Y Diao","year":"2022","unstructured":"Diao Y, Li Y, Wang Z, Wang S, Li P, Kong B. SF3B4 promotes ovarian cancer progression by regulating alternative splicing of RAD52. Cell Death Dis. 2022;13:179.","journal-title":"Cell Death Dis"},{"key":"8182_CR8","doi-asserted-by":"publisher","first-page":"6246","DOI":"10.1038\/s41467-022-34042-w","volume":"13","author":"Z Wang","year":"2022","unstructured":"Wang Z, Wang S, Qin J, Zhang X, Lu G, Liu H, et al. Splicing factor BUD31 promotes ovarian cancer progression through sustaining the expression of anti-apoptotic BCL2L12. Nat Commun. 2022;13:6246.","journal-title":"Nat Commun"},{"key":"8182_CR9","doi-asserted-by":"publisher","first-page":"e2306229","DOI":"10.1002\/advs.202306229","volume":"11","author":"X Liu","year":"2024","unstructured":"Liu X, Zhang J, Wang Z, Yan M, Xu M, Li G, et al. Splicing Factor PQBP1 Curtails BAX Expression to Promote Ovarian Cancer Progression. Adv Sci (Weinh). 2024;11:e2306229.","journal-title":"Adv Sci (Weinh)"},{"key":"8182_CR10","doi-asserted-by":"publisher","first-page":"3542","DOI":"10.1038\/s41375-021-01328-9","volume":"35","author":"DP Steensma","year":"2021","unstructured":"Steensma DP, Wermke M, Klimek VM, Greenberg PL, Font P, Komrokji RS, et al. Phase I First-in-Human Dose Escalation Study of the oral SF3B1 modulator H3B-8800 in myeloid neoplasms. Leukemia. 2021;35:3542\u201350.","journal-title":"Leukemia"},{"key":"8182_CR11","doi-asserted-by":"publisher","first-page":"779","DOI":"10.1016\/S1097-2765(00)80318-4","volume":"5","author":"R Das","year":"2000","unstructured":"Das R, Zhou Z, Reed R. Functional association of U2 snRNP with the ATP-independent spliceosomal complex E. Mol Cell. 2000;5:779\u201387.","journal-title":"Mol Cell"},{"key":"8182_CR12","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1101\/gad.10.2.233","volume":"10","author":"O Gozani","year":"1996","unstructured":"Gozani O, Feld R, Reed R. Evidence that sequence-independent binding of highly conserved U2 snRNP proteins upstream of the branch site is required for assembly of spliceosomal complex A. Genes Dev. 1996;10:233\u201343.","journal-title":"Genes Dev"},{"key":"8182_CR13","doi-asserted-by":"publisher","first-page":"846","DOI":"10.1038\/nature06842","volume":"452","author":"S Bessonov","year":"2008","unstructured":"Bessonov S, Anokhina M, Will CL, Urlaub H, L\u00fchrmann R. Isolation of an active step I spliceosome and composition of its RNP core. Nature. 2008;452:846\u201350.","journal-title":"Nature"},{"key":"8182_CR14","doi-asserted-by":"publisher","first-page":"37750","DOI":"10.18632\/oncotarget.5647","volume":"6","author":"J Tian","year":"2015","unstructured":"Tian J, Liu Y, Zhu B, Tian Y, Zhong R, Chen W, et al. SF3A1 and pancreatic cancer: new evidence for the association of the spliceosome and cancer. Oncotarget. 2015;6:37750\u20137.","journal-title":"Oncotarget"},{"key":"8182_CR15","first-page":"634","volume":"36","author":"W Song","year":"2015","unstructured":"Song W, Zhu B, Tian Y, Zhong R, Tian J, Miao X, et al. [Research on the association between U2-dependent spliceosome gene and hepatocellular cancer]. Zhonghua Liu Xing Bing Xue Za Zhi. 2015;36:634\u20138.","journal-title":"Zhonghua Liu Xing Bing Xue Za Zhi"},{"key":"8182_CR16","doi-asserted-by":"publisher","first-page":"e201800157","DOI":"10.26508\/lsa.201800157","volume":"1","author":"T Tabaglio","year":"2018","unstructured":"Tabaglio T, Low DH, Teo WKL, Goy PA, Cywoniuk P, Wollmann H, et al. MBNL1 alternative splicing isoforms play opposing roles in cancer. Life Sci Alliance. 2018;1:e201800157.","journal-title":"Life Sci Alliance"},{"key":"8182_CR17","doi-asserted-by":"publisher","first-page":"114764","DOI":"10.1016\/j.celrep.2024.114764","volume":"43","author":"BJ Woo","year":"2024","unstructured":"Woo BJ, Moussavi-Baygi R, Karner H, Karimzadeh M, Yousefi H, Lee S, et al. Integrative identification of non-coding regulatory regions driving metastatic prostate cancer. Cell Rep. 2024;43:114764.","journal-title":"Cell Rep"},{"key":"8182_CR18","doi-asserted-by":"publisher","first-page":"111228","DOI":"10.1016\/j.cellsig.2024.111228","volume":"120","author":"F Song","year":"2024","unstructured":"Song F, Hou C, Huang Y, Liang J, Cai H, Tian G, et al. Lactylome analyses suggest systematic lysine-lactylated substrates in oral squamous cell carcinoma under normoxia and hypoxia. Cell Signal. 2024;120:111228.","journal-title":"Cell Signal"},{"key":"8182_CR19","doi-asserted-by":"publisher","first-page":"2353","DOI":"10.7150\/jca.103209","volume":"16","author":"X Shuai","year":"2025","unstructured":"Shuai X, Sun Y, Liu S, Cheng Z. SF3a1: A Novel Potential Tumor Biomarker or Therapeutic Target. J Cancer. 2025;16:2353\u20139.","journal-title":"J Cancer"},{"key":"8182_CR20","doi-asserted-by":"publisher","first-page":"176835","DOI":"10.1016\/j.ejphar.2024.176835","volume":"979","author":"Q Chen","year":"2024","unstructured":"Chen Q, Sun Y, Li H, Liu S, Zhang H, Cheng Z, et al. Pixantrone as a novel MCM2 inhibitor for ovarian cancer treatment. Eur J Pharmacol. 2024;979:176835.","journal-title":"Eur J Pharmacol"},{"key":"8182_CR21","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1172\/JCI82534","volume":"126","author":"M Dewaele","year":"2016","unstructured":"Dewaele M, Tabaglio T, Willekens K, Bezzi M, Teo SX, Low DH, et al. Antisense oligonucleotide-mediated MDM4 exon 6 skipping impairs tumor growth. J Clin Invest. 2016;126:68\u201384.","journal-title":"J Clin Invest"},{"key":"8182_CR22","doi-asserted-by":"publisher","first-page":"E5593","DOI":"10.1073\/pnas.1419161111","volume":"111","author":"S Shen","year":"2014","unstructured":"Shen S, Park JW, Lu ZX, Lin L, Henry MD, Wu YN, et al. rMATS: robust and flexible detection of differential alternative splicing from replicate RNA-Seq data. Proc Natl Acad Sci U S A. 2014;111:E5593\u2013601.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"8182_CR23","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1126\/science.1233606","volume":"341","author":"D Martinez Molina","year":"2013","unstructured":"Martinez Molina D, Jafari R, Ignatushchenko M, Seki T, Larsson EA, Dan C, et al. Monitoring drug target engagement in cells and tissues using the cellular thermal shift assay. Science. 2013;341:84\u20137.","journal-title":"Science"},{"key":"8182_CR24","doi-asserted-by":"publisher","first-page":"21984","DOI":"10.1073\/pnas.0910040106","volume":"106","author":"B Lomenick","year":"2009","unstructured":"Lomenick B, Hao R, Jonai N, Chin RM, Aghajan M, Warburton S, et al. Target identification using drug affinity responsive target stability (DARTS). Proc Natl Acad Sci U S A. 2009;106:21984\u20139.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"8182_CR25","unstructured":"The Gene Expression Profiling Interactive Analysis Database. http:\/\/gepia2.cancer-pku.cn\/#index. Accessed 22 June 2025."},{"key":"8182_CR26","unstructured":"The Human Protein Atlas Database. https:\/\/www.proteinatlas.org. Accessed 15 April 2025."},{"key":"8182_CR27","unstructured":"The Kaplan\u2013Meier Plotter Database. https:\/\/www.kmplot.com. Accessed 30 June 2025."},{"key":"8182_CR28","first-page":"6091","volume":"59","author":"MJ Riemenschneider","year":"1999","unstructured":"Riemenschneider MJ, B\u00fcschges R, Wolter M, Reifenberger J, Bostr\u00f6m J, Kraus JA, et al. Amplification and overexpression of the MDM4 (MDMX) gene from 1q32 in a subset of malignant gliomas without TP53 mutation or MDM2 amplification. Cancer Res. 1999;59:6091\u20136.","journal-title":"Cancer Res"},{"key":"8182_CR29","first-page":"5864","volume":"11","author":"J Wu","year":"2021","unstructured":"Wu J, Lu G, Wang X. MDM4 alternative splicing and implication in MDM4 targeted cancer therapies. Am J Cancer Res. 2021;11:5864\u201380.","journal-title":"Am J Cancer Res"},{"key":"8182_CR30","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1186\/s12943-025-02268-z","volume":"24","author":"Y Lao","year":"2025","unstructured":"Lao Y, Jin Y, Wu S, Fang T, Wang Q, Sun L, et al. Correction: Deciphering a profiling based on multiple post-translational modifications functionally associated regulatory patterns and therapeutic opportunities in human hepatocellular carcinoma. Mol Cancer. 2025;24:49.","journal-title":"Mol Cancer"},{"key":"8182_CR31","unstructured":"The Phosphosite Database. https:\/\/www.phosphosite.org. Accessed 20 May 2024."},{"key":"8182_CR32","first-page":"260","volume":"1","author":"A Kr\u00e4mer","year":"1995","unstructured":"Kr\u00e4mer A, Mulhauser F, Wersig C, Gr\u00f6ning K, Bilbe G. Mammalian splicing factor SF3a120 represents a new member of the SURP family of proteins and is homologous to the essential splicing factor PRP21p of Saccharomyces cerevisiae. RNA. 1995;1:260\u201372.","journal-title":"RNA"},{"key":"8182_CR33","doi-asserted-by":"crossref","unstructured":"Lashen A, Algethami M, Alqahtani S, Shoqafi A, Sheha A, Jeyapalan JN, et al. The clinicopathological significance of the cyclin D1\/E1-cyclin-dependent kinase (CDK2\/4\/6)-Retinoblastoma (RB1\/pRB1) pathway in epithelial ovarian cancers. Int J Mol Sci. 2024; 25.","DOI":"10.3390\/ijms25074060"},{"key":"8182_CR34","doi-asserted-by":"publisher","first-page":"424","DOI":"10.1038\/s41392-023-01666-3","volume":"8","author":"J Qu","year":"2023","unstructured":"Qu J, Qiu B, Zhang Y, Hu Y, Wang Z, Guan Z, et al. The tumor-enriched small molecule gambogic amide suppresses glioma by targeting WDR1-dependent cytoskeleton remodeling. Signal Transduct Target Ther. 2023;8:424.","journal-title":"Signal Transduct Target Ther"},{"key":"8182_CR35","doi-asserted-by":"publisher","first-page":"3481","DOI":"10.1016\/j.apsb.2021.05.009","volume":"11","author":"R Huang","year":"2021","unstructured":"Huang R, Zhang L, Jin J, Zhou Y, Zhang H, Lv C, et al. Bruceine D inhibits HIF-1\u03b1-mediated glucose metabolism in hepatocellular carcinoma by blocking ICAT\/\u03b2-catenin interaction. Acta Pharm Sin B. 2021;11:3481\u201392.","journal-title":"Acta Pharm Sin B"},{"key":"8182_CR36","doi-asserted-by":"crossref","unstructured":"Madeddu C, Lai E, Neri M, Sanna E, Gramignano G, Nemolato S, et al. Association between TP53 mutations and platinum resistance in a cohort of high-grade serous ovarian cancer patients: novel implications for personalized therapeutics. Int J Mol Sci. 2025; 26.","DOI":"10.3390\/ijms26052232"},{"key":"8182_CR37","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1016\/j.ccell.2018.07.001","volume":"34","author":"A Kahles","year":"2018","unstructured":"Kahles A, Lehmann KV, Toussaint NC, H\u00fcser M, Stark SG, Sachsenberg T, et al. Comprehensive Analysis of Alternative Splicing Across Tumors from 8,705 Patients. Cancer Cell. 2018;34:211\u2013e2246.","journal-title":"Cancer Cell"},{"key":"8182_CR38","doi-asserted-by":"publisher","first-page":"eadj4009","DOI":"10.1126\/sciadv.adj4009","volume":"10","author":"L Deng","year":"2024","unstructured":"Deng L, Liao L, Zhang YL, Yang SY, Hu SY, Andriani L, et al. SF3A2 promotes progression and cisplatin resistance in triple-negative breast cancer via alternative splicing of MKRN1. Sci Adv. 2024;10:eadj4009.","journal-title":"Sci Adv"},{"key":"8182_CR39","doi-asserted-by":"crossref","unstructured":"Yu W, Gu Y, Zhang H, Huang W, Sun L, Ma L et al. SF3A3 Drives Tumorigenesis in endometrial cancer by enhancing c-FOS expression and represents a potential therapeutic target. Adv Sci (Weinh). 2025: e04184.","DOI":"10.1002\/advs.202504184"},{"key":"8182_CR40","doi-asserted-by":"publisher","first-page":"1366","DOI":"10.1091\/mbc.e04-11-1034","volume":"16","author":"G Tanackovic","year":"2005","unstructured":"Tanackovic G, Kr\u00e4mer A. Human splicing factor SF3a, but not SF1, is essential for pre-mRNA splicing in vivo. Mol Biol Cell. 2005;16:1366\u201377.","journal-title":"Mol Biol Cell"},{"key":"8182_CR41","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1038\/s41392-021-00486-7","volume":"6","author":"Y Zhang","year":"2021","unstructured":"Zhang Y, Qian J, Gu C, Yang Y. Alternative splicing and cancer: a systematic review. Signal Transduct Target Ther. 2021;6:78.","journal-title":"Signal Transduct Target Ther"},{"key":"8182_CR42","doi-asserted-by":"crossref","unstructured":"DuPont HL. Therapeutic Effects and mechanisms of action of rifaximin in gastrointestinal diseases. Mayo Clin Proc. 2015; 90: 1116-24.","DOI":"10.1016\/j.mayocp.2015.04.016"},{"key":"8182_CR43","doi-asserted-by":"publisher","first-page":"639","DOI":"10.3892\/ijo.2016.3550","volume":"49","author":"G Esposito","year":"2016","unstructured":"Esposito G, Gigli S, Seguella L, Nobile N, D\u2019Alessandro A, Pesce M, et al. Rifaximin, a non-absorbable antibiotic, inhibits the release of pro-angiogenic mediators in colon cancer cells through a pregnane X receptor-dependent pathway. Int J Oncol. 2016;49:639\u201345.","journal-title":"Int J Oncol"},{"key":"8182_CR44","doi-asserted-by":"publisher","first-page":"3512","DOI":"10.1039\/C7RA09689E","volume":"8","author":"S Gautam","year":"2018","unstructured":"Gautam S, Singh P, Singh M, Roy S, Rawat JK, Yadav RK, et al. Rifaximin, a pregnane X receptor (PXR) activator regulates apoptosis in a murine model of breast cancer. RSC Adv. 2018;8:3512\u201321.","journal-title":"RSC Adv"},{"key":"8182_CR45","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1124\/jpet.114.215913","volume":"351","author":"J Cheng","year":"2014","unstructured":"Cheng J, Fang ZZ, Nagaoka K, Okamoto M, Qu A, Tanaka N, et al. Activation of intestinal human pregnane X receptor protects against azoxymethane\/dextran sulfate sodium-induced colon cancer. J Pharmacol Exp Ther. 2014;351:559\u201367.","journal-title":"J Pharmacol Exp Ther"},{"key":"8182_CR46","doi-asserted-by":"publisher","first-page":"133582","DOI":"10.1016\/j.ijbiomac.2024.133582","volume":"275","author":"B Sun","year":"2024","unstructured":"Sun B, Xie W, Li X, Liu T, Bai J, Yao Y, et al. Inulin enhanced rifaximin-inhibited colon cancer pulmonary metastasis by flora-regulated bile acid pathway. Int J Biol Macromol. 2024;275:133582.","journal-title":"Int J Biol Macromol"},{"key":"8182_CR47","first-page":"2984","volume":"7","author":"A Reles","year":"2001","unstructured":"Reles A, Wen WH, Schmider A, Gee C, Runnebaum IB, Kilian U, et al. Correlation of p53 mutations with resistance to platinum-based chemotherapy and shortened survival in ovarian cancer. Clin Cancer Res. 2001;7:2984\u201397.","journal-title":"Clin Cancer Res"},{"key":"8182_CR48","doi-asserted-by":"publisher","first-page":"e1004932","DOI":"10.1371\/journal.pgen.1004932","volume":"11","author":"BP O\u2019Connor","year":"2015","unstructured":"O\u2019Connor BP, Danhorn T, De Arras L, Flatley BR, Marcus RA, Farias-Hesson E, et al. Regulation of toll-like receptor signaling by the SF3a mRNA splicing complex. PLoS Genet. 2015;11:e1004932.","journal-title":"PLoS Genet"},{"key":"8182_CR49","doi-asserted-by":"publisher","first-page":"e1003855","DOI":"10.1371\/journal.pgen.1003855","volume":"9","author":"L De Arras","year":"2013","unstructured":"De Arras L, Alper S. Limiting of the innate immune response by SF3A-dependent control of MyD88 alternative mRNA splicing. PLoS Genet. 2013;9:e1003855.","journal-title":"PLoS Genet"},{"key":"8182_CR50","doi-asserted-by":"publisher","first-page":"946","DOI":"10.1016\/j.ccell.2024.04.009","volume":"42","author":"Y Liu","year":"2024","unstructured":"Liu Y, Su Z, Tavana O, Gu W. Understanding the complexity of p53 in a new era of tumor suppression. Cancer Cell. 2024;42:946\u201367.","journal-title":"Cancer Cell"},{"key":"8182_CR51","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1038\/s41568-023-00658-3","volume":"24","author":"S Peuget","year":"2024","unstructured":"Peuget S, Zhou X, Selivanova G. Translating p53-based therapies for cancer into the clinic. Nat Rev Cancer. 2024;24:192\u2013215.","journal-title":"Nat Rev Cancer"},{"key":"8182_CR52","doi-asserted-by":"crossref","unstructured":"Patrick N, Markey M. Long-Read MDM4 Sequencing Reveals aberrant isoform landscape in metastatic melanomas. Int J Mol Sci. 2024; 25.","DOI":"10.3390\/ijms25179415"},{"key":"8182_CR53","doi-asserted-by":"publisher","first-page":"1903","DOI":"10.1101\/gad.219899.113","volume":"27","author":"M Bezzi","year":"2013","unstructured":"Bezzi M, Teo SX, Muller J, Mok WC, Sahu SK, Vardy LA, et al. Regulation of constitutive and alternative splicing by PRMT5 reveals a role for Mdm4 pre-mRNA in sensing defects in the spliceosomal machinery. Genes Dev. 2013;27:1903\u201316.","journal-title":"Genes Dev"},{"key":"8182_CR54","first-page":"876173","volume":"2011","author":"K Lenos","year":"2011","unstructured":"Lenos K, Jochemsen AG. Functions of MDMX in the modulation of the p53-response. J Biomed Biotechnol. 2011;2011:876173.","journal-title":"J Biomed Biotechnol"},{"key":"8182_CR55","doi-asserted-by":"publisher","first-page":"8299","DOI":"10.1074\/jbc.274.12.8299","volume":"274","author":"R Rallapalli","year":"1999","unstructured":"Rallapalli R, Strachan G, Cho B, Mercer WE. Hall. A novel MDMX transcript expressed in a variety of transformed cell lines encodes a truncated protein with potent p53 repressive activity. J Biol Chem. 1999;274:8299\u2013308.","journal-title":"J Biol Chem"},{"key":"8182_CR56","doi-asserted-by":"publisher","first-page":"452","DOI":"10.1016\/j.molcel.2020.10.022","volume":"80","author":"KT Bieging-Rolett","year":"2020","unstructured":"Bieging-Rolett KT, Kaiser AM, Morgens DW, Boutelle AM, Seoane JA, Van Nostrand EL, et al. Zmat3 Is a Key Splicing Regulator in the p53 Tumor Suppression Program. Mol Cell. 2020;80:452\u2013e4699.","journal-title":"Mol Cell"},{"key":"8182_CR57","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/onc.2012.38","volume":"32","author":"N Allende-Vega","year":"2013","unstructured":"Allende-Vega N, Dayal S, Agarwala U, Sparks A, Bourdon JC. Saville. p53 is activated in response to disruption of the pre-mRNA splicing machinery. Oncogene. 2013;32:1\u201314.","journal-title":"Oncogene"},{"key":"8182_CR58","doi-asserted-by":"publisher","first-page":"534","DOI":"10.1002\/1878-0261.12052","volume":"11","author":"E Siebring-van Olst","year":"2017","unstructured":"Siebring-van Olst E, Blijlevens M, de Menezes RX, van der Meulen-Muileman IH, Smit EF, van Beusechem VW. A genome-wide siRNA screen for regulators of tumor suppressor p53 activity in human non-small cell lung cancer cells identifies components of the RNA splicing machinery as targets for anticancer treatment. Mol Oncol. 2017;11:534\u201351.","journal-title":"Mol Oncol"},{"key":"8182_CR59","doi-asserted-by":"publisher","first-page":"e14301","DOI":"10.1111\/acel.14301","volume":"23","author":"M Desch\u00eanes","year":"2024","unstructured":"Desch\u00eanes M, Durand M, Olivier MA, Pellerin-Viger A. Rodier and B. Chabot. A defective splicing machinery promotes senescence through MDM4 alternative splicing. Aging Cell. 2024;23:e14301.","journal-title":"Aging Cell"},{"key":"8182_CR60","doi-asserted-by":"publisher","first-page":"9644","DOI":"10.1073\/pnas.2005945117","volume":"117","author":"S AbuHammad","year":"2020","unstructured":"AbuHammad S, Cullinane C, Martin C, Bacolas Z, Ward T, Chen H, et al., et al. Correction for AbuHammad et al., Regulation of PRMT5-MDM4 axis is critical in the response to CDK4\/6 inhibitors in melanoma. Proc Natl Acad Sci U S A. 2020;117:9644\u20135.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"8182_CR61","unstructured":"Danovi D, Meulmeester E, Pasini D, Migliorini D, Capra M, Frenk R, et al. Correction for danovi amplification of Mdmx (or Mdm4) directly contributes to tumor formation by inhibiting p53 tumor suppressor activity. Mol Cell Biol. 2019; 39."},{"key":"8182_CR62","doi-asserted-by":"publisher","first-page":"3915","DOI":"10.1111\/cas.16356","volume":"115","author":"S Yu","year":"2024","unstructured":"Yu S, Si Y, Yu J, Jiang C, Cheng F, Xu M, et al. SNRPB2 promotes triple-negative breast cancer progression by controlling alternative splicing of MDM4 pre-mRNA. Cancer Sci. 2024;115:3915\u201327.","journal-title":"Cancer Sci"},{"key":"8182_CR63","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1016\/j.jconrel.2014.08.023","volume":"194","author":"LY Peddada","year":"2014","unstructured":"Peddada LY, Garbuzenko OB, Devore DI, Minko T, Roth CM. Delivery of antisense oligonucleotides using poly(alkylene oxide)-poly(propylacrylic acid) graft copolymers in conjunction with cationic liposomes. J Control Release. 2014;194:103\u201312.","journal-title":"J Control Release"},{"key":"8182_CR64","first-page":"3606","volume":"7","author":"N Sato","year":"2001","unstructured":"Sato N, Kobayashi H, Saga T, Nakamoto Y, Ishimori T, Togashi K, et al. Tumor targeting and imaging of intraperitoneal tumors by use of antisense oligo-DNA complexed with dendrimers and\/or avidin in mice. Clin Cancer Res. 2001;7:3606\u201312.","journal-title":"Clin Cancer Res"},{"key":"8182_CR65","doi-asserted-by":"publisher","first-page":"861","DOI":"10.1016\/j.jconrel.2022.10.050","volume":"352","author":"T Ramasamy","year":"2022","unstructured":"Ramasamy T, Ruttala HB, Munusamy S, Chakraborty N, Kim JO. Nano drug delivery systems for antisense oligonucleotides (ASO) therapeutics. J Control Release. 2022;352:861\u201378.","journal-title":"J Control Release"},{"key":"8182_CR66","doi-asserted-by":"publisher","first-page":"6406","DOI":"10.1128\/MCB.21.19.6406-6417.2001","volume":"21","author":"D Nesic","year":"2001","unstructured":"Nesic D, Kr\u00e4mer A. Domains in human splicing factors SF3a60 and SF3a66 required for binding to SF3a120, assembly of the 17S U2 snRNP, and prespliceosome formation. Mol Cell Biol. 2001;21:6406\u201317.","journal-title":"Mol Cell Biol"},{"key":"8182_CR67","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/j.phrs.2014.05.001","volume":"85","author":"C Blandizzi","year":"2014","unstructured":"Blandizzi C, Viscomi GC, Marzo A, Scarpignato C. Is generic rifaximin still a poorly absorbed antibiotic? A comparison of branded and generic formulations in healthy volunteers. Pharmacol Res. 2014;85:39\u201344.","journal-title":"Pharmacol Res"},{"key":"8182_CR68","doi-asserted-by":"publisher","first-page":"e27131","DOI":"10.1016\/j.heliyon.2024.e27131","volume":"10","author":"I Toukabri","year":"2024","unstructured":"Toukabri I, Bahri S, Sfar S, Lassoued MA. Impact of crystal polymorphism of rifaximin on dissolution behavior. Heliyon. 2024;10:e27131.","journal-title":"Heliyon"},{"key":"8182_CR69","doi-asserted-by":"crossref","unstructured":"Zhuo X, Margrethe Brekstad Kjellin M, Schaal Z, Zhang T, L\u00f6bmann K. and D. Leng. A Comparative Study between A Protein Based Amorphous Formulation and Other Dissolution Rate Enhancing Approaches: A Case Study with Rifaximin. Pharmaceutics. 2022; 15.","DOI":"10.3390\/pharmaceutics15010126"},{"key":"8182_CR70","doi-asserted-by":"publisher","first-page":"116782","DOI":"10.1016\/j.carbpol.2020.116782","volume":"248","author":"SA Algharib","year":"2020","unstructured":"Algharib SA, Dawood A, Zhou K, Chen D, Li C, Meng K, et al. Designing, structural determination and biological effects of rifaximin loaded chitosan- carboxymethyl chitosan nanogel. Carbohydr Polym. 2020;248:116782.","journal-title":"Carbohydr Polym"},{"key":"8182_CR71","doi-asserted-by":"publisher","first-page":"116978","DOI":"10.1016\/j.carbpol.2020.116978","volume":"252","author":"ACC Vieira","year":"2021","unstructured":"Vieira ACC, Chaves LL, Pinheiro M, Lima SC, Neto PJR, Ferreira D, et al. Lipid nanoparticles coated with chitosan using a one-step association method to target rifampicin to alveolar macrophages. Carbohydr Polym. 2021;252:116978.","journal-title":"Carbohydr Polym"},{"key":"8182_CR72","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1186\/s13045-021-01096-0","volume":"14","author":"Z Cheng","year":"2021","unstructured":"Cheng Z, Li M, Dey R, Chen Y. Nanomaterials for cancer therapy: current progress and perspectives. J Hematol Oncol. 2021;14:85.","journal-title":"J Hematol Oncol"}],"container-title":["Journal of Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12967-026-08182-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12967-026-08182-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12967-026-08182-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T00:04:45Z","timestamp":1781481885000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s12967-026-08182-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,27]]},"references-count":72,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["8182"],"URL":"https:\/\/doi.org\/10.1186\/s12967-026-08182-2","relation":{},"ISSN":["1479-5876"],"issn-type":[{"value":"1479-5876","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,27]]},"assertion":[{"value":"24 November 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 April 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 April 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 study was conducted in accordance with the Declarations of Helsinki. OC and ovary tissue samples were obtained from surgical resections at the Department of Gynecology, Shanghai Tenth People\u2019s Hospital, Tongji University School of Medicine. All patients provided informed consents and ethical approval was approved by the Bioethics Committee for Human Biomedical Research of Tongji University (2023tjdxsy011). In addition, the animal experiments conformed to Guide for the Care and Use of Laboratory Animals, and were approved by the Animal Experimental Ethics Committee of the Shanghai Tenth People\u2019s Hospital (SHDSYY-2025-4446).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"SPL, XQS are inventors on a patent application titled \u201cThe application of rifaximin in cancer treatment\u201d (filing number 2025106360969) and another patent application titled \u201cAn oligonucleotide for treating tumors\u201d (filing number 2025107129331). The authors declare no other potential conflicts of interest.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"768"}}