{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T17:58:51Z","timestamp":1780941531548,"version":"3.54.1"},"reference-count":41,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T00:00:00Z","timestamp":1780876800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32070818"],"award-info":[{"award-number":["32070818"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Guangdong Hybribio Biotech Funding","award":["H20230314"],"award-info":[{"award-number":["H20230314"]}]},{"name":"Guangdong Hybribio Biotech Funding","award":["H20230311"],"award-info":[{"award-number":["H20230311"]}]},{"name":"Guangdong Hybribio Biotech Funding","award":["H20230313"],"award-info":[{"award-number":["H20230313"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    EP300, a frequently mutated transcriptional coactivator in bladder cancer, has been demonstrated to positively correlate with malignancy in various cancers. Highly aggressive bladder cancers are often associated with muscle-invasive progression, a process closely linked to the epithelial-mesenchymal transition (EMT) capability of bladder cancer. Here, we performed immunohistochemical staining on bladder cancer tissues and adjacent normal tissues obtained from radical cystectomy to validate the positive association between EP300 and bladder cancer malignancy. We observed that A485, a small-molecule inhibitor of EP300, significantly inhibited cell migration in multiple bladder cancer cell lines (SW780, T24, RT4 and 5637) both in scratch wound healing and Transwell assays. Additionally, take the advantage of organoid-3D culture system, A485 disrupted the formation of inter-organoids connecting tubular structures in T24 cell line, while A485 also disrupted the organoid migration from matrix out-toward the non-matrix region both in SW780 and 5637 cell lines. In\n                    <jats:italic>in vivo<\/jats:italic>\n                    experiment, A485 showed a trend toward inhibiting BBN-induced bladder cancer invasion in mice. Bulk RNAseq analysis revealed that A485 commonly downregulated SNAI2-related signaling pathways across multiple bladder cancer cell lines. Furthermore, western blotting confirmed that A485 significantly reduced the global level of acetylation of histone H3 at lysine 27 (H3K27ac) as well as SNAI2 expression in T24 and SW780 cell lines. Indeed, overexpression of SNAI2 enhanced the migratory capacity of bladder cancer cells via Transwell assay. Collectively, our findings demonstrate that EP300 promoted bladder cancer cell migration via up-regulating SNAI2, targeting EP300 could be a potential therapeutic strategy to inhibit the process of bladder cancer invasion.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0347209","type":"journal-article","created":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T17:25:53Z","timestamp":1780939553000},"page":"e0347209","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["EP300 promotes bladder cancer cell migration through SNAI2"],"prefix":"10.1371","volume":"21","author":[{"given":"Qing","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chongjie","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingzhou","family":"Hong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuangsheng","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Peng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haifeng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-6141-0037","authenticated-orcid":true,"given":"Chunming","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,6,8]]},"reference":[{"issue":"10","key":"pone.0347209.ref001","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1038\/s41568-024-00725-3","article-title":"The impact of sex on metastasis","volume":"24","author":"Y Zhang","year":"2024","journal-title":"Nat Rev Cancer"},{"issue":"8","key":"pone.0347209.ref002","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1038\/s41585-022-00591-4","article-title":"Sex differences in bladder cancer: emerging data and call to action","volume":"19","author":"D Theodorescu","year":"2022","journal-title":"Nat Rev Urol"},{"issue":"10364","key":"pone.0347209.ref003","doi-asserted-by":"crossref","first-page":"1712","DOI":"10.1016\/S0140-6736(22)01188-6","article-title":"Current best practice for bladder cancer: a narrative review of diagnostics and treatments","volume":"400","author":"E Comp\u00e9rat","year":"2022","journal-title":"Lancet"},{"issue":"7","key":"pone.0347209.ref004","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1038\/s41585-023-00847-7","article-title":"Molecular profile of bladder cancer progression to clinically aggressive subtypes","volume":"21","author":"CC Guo","year":"2024","journal-title":"Nat Rev Urol"},{"issue":"2","key":"pone.0347209.ref005","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1016\/j.cell.2018.03.059","article-title":"SnapShot: TCGA-Analyzed Tumors","volume":"173","author":"A Blum","year":"2018","journal-title":"Cell"},{"issue":"2","key":"pone.0347209.ref006","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1038\/s41568-020-00313-1","article-title":"Advances in bladder cancer biology and therapy","volume":"21","author":"L Tran","year":"2021","journal-title":"Nat Rev Cancer"},{"issue":"2","key":"pone.0347209.ref007","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1007\/s10549-018-4927-3","article-title":"Somatic EP300-G211S mutations are associated with overall somatic mutational patterns and breast cancer specific survival in triple-negative breast cancer","volume":"172","author":"V Bemanian","year":"2018","journal-title":"Breast Cancer Res Treat"},{"key":"pone.0347209.ref008","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.oraloncology.2019.06.032","article-title":"Immune profiles in primary squamous cell carcinoma of the head and neck","volume":"96","author":"V Saloura","year":"2019","journal-title":"Oral Oncol"},{"issue":"4","key":"pone.0347209.ref009","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1158\/2159-8290.CD-15-0754","article-title":"Targeting p300 Addiction in CBP-Deficient Cancers Causes Synthetic Lethality by Apoptotic Cell Death due to Abrogation of MYC Expression","volume":"6","author":"H Ogiwara","year":"2016","journal-title":"Cancer Discov"},{"issue":"4","key":"pone.0347209.ref010","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.3390\/cancers15041219","article-title":"The Role of CREBBP\/EP300 and Its Therapeutic Implications in Hematological Malignancies","volume":"15","author":"Y Zhu","year":"2023","journal-title":"Cancers (Basel)"},{"issue":"4","key":"pone.0347209.ref011","article-title":"Genetic dysregulation of EP300 in cancers in light of cancer epigenome control \u2013 targeting of p300-proficient and -deficient cancers. Molecular Therapy:","volume":"32","author":"K Gronkowska","year":"2024","journal-title":"Oncology"},{"issue":"11","key":"pone.0347209.ref012","doi-asserted-by":"crossref","first-page":"2095","DOI":"10.1158\/1078-0432.CCR-22-3836","article-title":"A tumor-suppressive molecular axis EP300\/circRERE\/miR-6837-3p\/MAVS activates type I IFN pathway and antitumor immunity to suppress colorectal cancer","volume":"29","author":"N Ding","year":"2023","journal-title":"Clinical Cancer Research"},{"issue":"3","key":"pone.0347209.ref013","doi-asserted-by":"crossref","first-page":"2132","DOI":"10.18632\/aging.102728","article-title":"EP300 mutation is associated with tumor mutation burden and promotes antitumor immunity in bladder cancer patients","volume":"12","author":"G Zhu","year":"2020","journal-title":"Aging (Albany NY)"},{"issue":"1","key":"pone.0347209.ref014","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/s10020-023-00608-7","article-title":"Experimental analysis of bladder cancer-associated mutations in EP300 identifies EP300-R1627W as a driver mutation","volume":"29","author":"M Luo","year":"2023","journal-title":"Mol Med"},{"issue":"9","key":"pone.0347209.ref015","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1038\/ng.907","article-title":"Frequent mutations of chromatin remodeling genes in transitional cell carcinoma of the bladder","volume":"43","author":"Y Gui","year":"2011","journal-title":"Nat Genet"},{"issue":"12","key":"pone.0347209.ref016","doi-asserted-by":"crossref","first-page":"2136","DOI":"10.1016\/j.ccell.2023.11.001","article-title":"Therapeutic targeting of EP300\/CBP by bromodomain inhibition in hematologic malignancies","volume":"41","author":"L Nicosia","year":"2023","journal-title":"Cancer Cell"},{"issue":"1","key":"pone.0347209.ref017","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1186\/s12967-023-04043-4","article-title":"EGR1 induces EMT in pancreatic cancer via a P300\/SNAI2 pathway","volume":"21","author":"Y Wang","year":"2023","journal-title":"J Transl Med"},{"issue":"5","key":"pone.0347209.ref018","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1016\/j.stem.2024.04.004","article-title":"Hallmarks of cancer stemness","volume":"31","author":"J-J Loh","year":"2024","journal-title":"Cell Stem Cell"},{"issue":"8","key":"pone.0347209.ref019","doi-asserted-by":"crossref","first-page":"3404","DOI":"10.1128\/MCB.24.8.3404-3414.2004","article-title":"Acetylation of \u03b2-Catenin by p300 regulates \u03b2-Catenin-Tcf4 interaction","volume":"24","author":"L L\u00e9vy","year":"2023","journal-title":"Molecular and Cellular Biology"},{"issue":"12","key":"pone.0347209.ref020","doi-asserted-by":"crossref","first-page":"6569","DOI":"10.1074\/jbc.M115.706416","article-title":"p300\/\u03b2-Catenin Interactions Regulate Adult Progenitor Cell Differentiation Downstream of WNT5a\/Protein Kinase C (PKC)","volume":"291","author":"ME Rieger","year":"2016","journal-title":"J Biol Chem"},{"issue":"23","key":"pone.0347209.ref021","doi-asserted-by":"crossref","first-page":"12613","DOI":"10.1073\/pnas.220158597","article-title":"Regulation of beta -catenin transformation by the p300 transcriptional coactivator","volume":"97","author":"Y Sun","year":"2000","journal-title":"Proc Natl Acad Sci U S A"},{"key":"pone.0347209.ref022","doi-asserted-by":"crossref","first-page":"107306","DOI":"10.1016\/j.phrs.2024.107306","article-title":"Apabetalone, a BET protein inhibitor, inhibits kidney damage in diabetes by preventing pyroptosis via modulating the P300\/H3K27ac\/PLK1 axis","volume":"207","author":"M Wang","year":"2024","journal-title":"Pharmacol Res"},{"key":"pone.0347209.ref023","doi-asserted-by":"crossref","first-page":"8828367","DOI":"10.1155\/2024\/8828367","article-title":"Cryptotanshinone Inhibits Bladder Cancer Cell Malignant Progression in a Lipopolysaccharide-Induced Inflammatory Microenvironment through NLRP3 Inhibition","volume":"2024","author":"C Tang","year":"2024","journal-title":"Mediators Inflamm"},{"issue":"4","key":"pone.0347209.ref024","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1016\/j.ccell.2014.09.001","article-title":"Hedgehog signaling restrains bladder cancer progression by eliciting stromal production of urothelial differentiation factors","volume":"26","author":"K Shin","year":"2014","journal-title":"Cancer Cell"},{"issue":"5","key":"pone.0347209.ref025","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1038\/ncb2956","article-title":"Cellular origin of bladder neoplasia and tissue dynamics of its progression to invasive carcinoma","volume":"16","author":"K Shin","year":"2014","journal-title":"Nat Cell Biol"},{"issue":"1","key":"pone.0347209.ref026","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","article-title":"STAR: ultrafast universal RNA-seq aligner","volume":"29","author":"A Dobin","year":"2013","journal-title":"Bioinformatics"},{"issue":"10","key":"pone.0347209.ref027","doi-asserted-by":"crossref","first-page":"2943","DOI":"10.1093\/bioinformatics\/btac166","article-title":"Analysing high-throughput sequencing data in Python with HTSeq 2.0","volume":"38","author":"GH Putri","year":"2022","journal-title":"Bioinformatics"},{"key":"pone.0347209.ref028","article-title":"edgeR 4.0: powerful differential analysis of sequencing data with expanded functionality and improved support for small counts and larger datasets","volume":"2024","author":"Y Chen","journal-title":"bioRxiv"},{"issue":"7","key":"pone.0347209.ref029","doi-asserted-by":"crossref","DOI":"10.1093\/nar\/gkv007","article-title":"limma powers differential expression analyses for RNA-sequencing and microarray studies","volume":"43","author":"ME Ritchie","year":"2015","journal-title":"Nucleic Acids Res"},{"issue":"11","key":"pone.0347209.ref030","doi-asserted-by":"crossref","first-page":"3292","DOI":"10.1038\/s41596-024-01020-z","article-title":"Using clusterProfiler to characterize multiomics data","volume":"19","author":"S Xu","year":"2024","journal-title":"Nat Protoc"},{"issue":"1","key":"pone.0347209.ref031","doi-asserted-by":"crossref","first-page":"1787","DOI":"10.1038\/s41467-023-37544-3","article-title":"MYC reshapes CTCF-mediated chromatin architecture in prostate cancer","volume":"14","author":"Z Wei","year":"2023","journal-title":"Nat Commun"},{"issue":"3","key":"pone.0347209.ref032","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1158\/2159-8290.CD-21-0385","article-title":"EP300 Selectively Controls the Enhancer Landscape of MYCN-Amplified Neuroblastoma","volume":"12","author":"AD Durbin","year":"2022","journal-title":"Cancer Discov"},{"issue":"7","key":"pone.0347209.ref033","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1016\/j.cell.2004.06.006","article-title":"Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis","volume":"117","author":"J Yang","year":"2004","journal-title":"Cell"},{"issue":"16","key":"pone.0347209.ref034","doi-asserted-by":"crossref","first-page":"3917","DOI":"10.1158\/1078-0432.CCR-17-3775","article-title":"\u0394Np63\u03b3\/SRC\/Slug Signaling Axis Promotes Epithelial-to-Mesenchymal Transition in Squamous Cancers","volume":"24","author":"K Srivastava","year":"2018","journal-title":"Clin Cancer Res"},{"issue":"7","key":"pone.0347209.ref035","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0068923","article-title":"Cancer-associated fibroblasts promote proliferation of endometrial cancer cells","volume":"8","author":"KS Subramaniam","year":"2013","journal-title":"PLoS One"},{"issue":"6","key":"pone.0347209.ref036","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.1083\/jcb.137.6.1403","article-title":"The zinc-finger protein slug causes desmosome dissociation, an initial and necessary step for growth factor-induced epithelial-mesenchymal transition","volume":"137","author":"P Savagner","year":"1997","journal-title":"J Cell Biol"},{"issue":"13","key":"pone.0347209.ref037","doi-asserted-by":"crossref","first-page":"6618","DOI":"10.1093\/nar\/gkt410","article-title":"IGF2BP1 promotes mesenchymal cell properties and migration of tumor-derived cells by enhancing the expression of LEF1 and SNAI2 (SLUG)","volume":"41","author":"A Zirkel","year":"2013","journal-title":"Nucleic Acids Res"},{"issue":"1","key":"pone.0347209.ref038","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1186\/s13046-022-02541-9","article-title":"LncRNA ELF3-AS1 inhibits gastric cancer by forming a negative feedback loop with SNAI2 and regulates ELF3 mRNA stability via interacting with ILF2\/ILF3 complex","volume":"41","author":"D Li","year":"2022","journal-title":"J Exp Clin Cancer Res"},{"key":"pone.0347209.ref039","doi-asserted-by":"crossref","first-page":"113914","DOI":"10.1016\/j.bcp.2020.113914","article-title":"A novel histone acetyltransferase inhibitor A485 improves sensitivity of non-small-cell lung carcinoma cells to TRAIL","volume":"175","author":"B Zhang","year":"2020","journal-title":"Biochem Pharmacol"},{"issue":"7674","key":"pone.0347209.ref040","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1038\/nature24028","article-title":"Discovery of a selective catalytic p300\/CBP inhibitor that targets lineage-specific tumours","volume":"550","author":"LM Lasko","year":"2017","journal-title":"Nature"},{"issue":"2","key":"pone.0347209.ref041","doi-asserted-by":"crossref","DOI":"10.1016\/j.immuni.2024.01.005","article-title":"Small-molecule CBP\/p300 histone acetyltransferase inhibition mobilizes leukocytes from the bone marrow via the endocrine stress response","volume":"57","author":"NP Jaschke","year":"2024","journal-title":"Immunity"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0347209","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T17:26:01Z","timestamp":1780939561000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0347209"}},"subtitle":[],"editor":[{"given":"Habib","family":"Boukerche","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,6,8]]},"references-count":41,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2026,6,8]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0347209","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,8]]}}}