{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T18:14:30Z","timestamp":1789582470403,"version":"build-2803163510"},"reference-count":112,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2024,1,11]],"date-time":"2024-01-11T00:00:00Z","timestamp":1704931200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["HD094378"],"award-info":[{"award-number":["HD094378"]}]},{"name":"NIH","award":["ES028615"],"award-info":[{"award-number":["ES028615"]}]},{"name":"NIH","award":["MD007602"],"award-info":[{"award-number":["MD007602"]}]},{"name":"NIH","award":["HD094380"],"award-info":[{"award-number":["HD094380"]}]},{"name":"NIH","award":["HD087417"],"award-info":[{"award-number":["HD087417"]}]},{"name":"NIH","award":["HD106285"],"award-info":[{"award-number":["HD106285"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Bromodomain-containing proteins (BRDs) are involved in many biological processes, most notably epigenetic regulation of transcription, and BRD dysfunction has been linked to many diseases, including tumorigenesis. However, the role of BRDs in the pathogenesis of uterine fibroids (UFs) is entirely unknown. The present study aimed to determine the expression pattern of BRD9 in UFs and matched myometrium and further assess the impact of a BRD9 inhibitor on UF phenotype and epigenetic\/epitranscriptomic changes. Our studies demonstrated that the levels of BRD9 were significantly upregulated in UFs compared to matched myometrium, suggesting that the aberrant BRD expression may contribute to the pathogenesis of UFs. We then evaluated the potential roles of BRD9 using its specific inhibitor, I-BRD9. Targeted inhibition of BRD9 suppressed UF tumorigenesis with increased apoptosis and cell cycle arrest, decreased cell proliferation, and extracellular matrix deposition in UF cells. The latter is the key hallmark of UFs. Unbiased transcriptomic profiling coupled with downstream bioinformatics analysis further and extensively demonstrated that targeted inhibition of BRD9 impacted the cell cycle- and ECM-related biological pathways and reprogrammed the UF cell epigenome and epitranscriptome in UFs. Taken together, our studies support the critical role of BRD9 in UF cells and the strong interconnection between BRD9 and other pathways controlling the UF progression. Targeted inhibition of BRDs might provide a non-hormonal treatment option for this most common benign tumor in women of reproductive age.<\/jats:p>","DOI":"10.3390\/ijms25020905","type":"journal-article","created":{"date-parts":[[2024,1,11]],"date-time":"2024-01-11T06:52:14Z","timestamp":1704955934000},"page":"905","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Bromodomain-Containing Protein 9 Regulates Signaling Pathways and Reprograms the Epigenome in Immortalized Human Uterine Fibroid Cells"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7131-8946","authenticated-orcid":false,"given":"Qiwei","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, University of Chicago, 5841 S. Maryland Ave., Chicago, IL 60637, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Somayeh","family":"Vafaei","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University of Chicago, 5841 S. Maryland Ave., Chicago, IL 60637, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Falahati","sequence":"additional","affiliation":[{"name":"DNA GTx LAB, Dubai Healthcare City, Dubai 505262, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Azad","family":"Khosh","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, Institute of Biotechnology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2675-7936","authenticated-orcid":false,"given":"Maria Victoria","family":"Bariani","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University of Chicago, 5841 S. Maryland Ave., Chicago, IL 60637, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mervat M.","family":"Omran","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University of Chicago, 5841 S. Maryland Ave., Chicago, IL 60637, USA"},{"name":"Cancer Biology Department, National Cancer Institute, Cairo University, Cairo 11796, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Bai","sequence":"additional","affiliation":[{"name":"Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiba","family":"Siblini","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University of Chicago, 5841 S. Maryland Ave., Chicago, IL 60637, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9675-6691","authenticated-orcid":false,"given":"Mohamed","family":"Ali","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University of Chicago, 5841 S. Maryland Ave., Chicago, IL 60637, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuan","family":"He","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Chicago, Chicago, IL 60637, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas G.","family":"Boyer","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, Institute of Biotechnology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8778-4447","authenticated-orcid":false,"given":"Ayman","family":"Al-Hendy","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University of Chicago, 5841 S. Maryland Ave., Chicago, IL 60637, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1210\/endrev\/bnab039","article-title":"Comprehensive Review of Uterine Fibroids: Developmental Origin, Pathogenesis, and Treatment","volume":"43","author":"Yang","year":"2022","journal-title":"Endocr. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1344","DOI":"10.1056\/NEJMra1209993","article-title":"Uterine fibroids","volume":"369","author":"Bulun","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"16043","DOI":"10.1038\/nrdp.2016.43","article-title":"Uterine fibroids","volume":"2","author":"Stewart","year":"2016","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1055\/s-0037-1607295","article-title":"The Effect of Uterine Fibroids on Infertility: A Systematic Review","volume":"35","author":"Whynott","year":"2017","journal-title":"Semin. Reprod. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1038\/s41392-019-0095-0","article-title":"Targeting epigenetic regulators for cancer therapy: Mechanisms and advances in clinical trials","volume":"4","author":"Cheng","year":"2019","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1177\/1933719115584449","article-title":"The Mechanism and Function of Epigenetics in Uterine Leiomyoma Development","volume":"23","author":"Yang","year":"2016","journal-title":"Reprod. Sci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1038\/s41586-021-03747-1","article-title":"Deficient H2A.Z deposition is associated with genesis of uterine leiomyoma","volume":"596","author":"Berta","year":"2021","journal-title":"Nature"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2960","DOI":"10.1007\/s43032-022-00981-4","article-title":"Differential Expression of Super-Enhancer-Associated Long Non-coding RNAs in Uterine Leiomyomas","volume":"29","author":"Chuang","year":"2022","journal-title":"Reprod. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1016\/j.fertnstert.2020.07.024","article-title":"Functional role of the long noncoding RNA X-inactive specific transcript in leiomyoma pathogenesis","volume":"115","author":"Chuang","year":"2021","journal-title":"Fertil. Steril."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Carbajo-Garcia, M.C., Juarez-Barber, E., Segura-Benitez, M., Faus, A., Trelis, A., Monleon, J., Carmona-Antonanzas, G., Pellicer, A., Flanagan, J.M., and Ferrero, H. (2023). H3K4me3 mediates uterine leiomyoma pathogenesis via neuronal processes, synapsis components, proliferation, and Wnt\/beta-catenin and TGF-beta pathways. Reprod. Biol. Endocrinol., 21.","DOI":"10.1186\/s12958-023-01060-2"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e160274","DOI":"10.1172\/jci.insight.160274","article-title":"Transcriptome and DNA methylome analyses reveal underlying mechanisms for the racial disparity in uterine fibroids","volume":"7","author":"Paul","year":"2022","journal-title":"JCI Insight"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1002\/path.5920","article-title":"Integrative analysis of the DNA methylome and transcriptome in uterine leiomyoma shows altered regulation of genes involved in metabolism, proliferation, extracellular matrix, and vesicles","volume":"257","author":"Corachan","year":"2022","journal-title":"J. Pathol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1007\/s00018-023-04919-0","article-title":"Developmental reprogramming of myometrial stem cells by endocrine disruptor linking to risk of uterine fibroids","volume":"80","author":"Yang","year":"2023","journal-title":"Cell Mol. Life Sci."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Yang, Q., Ali, M., Trevino, L.S., Mas, A., Ismail, N., and Al-Hendy, A. (2023). Epigenetic Modulation of Inflammatory Pathways in Myometrial Stem Cells and Risk of Uterine Fibroids. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241411641"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1038\/cr.2011.42","article-title":"Readers of histone modifications","volume":"21","author":"Yun","year":"2011","journal-title":"Cell Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2003","DOI":"10.1016\/j.jmb.2016.11.020","article-title":"Bromodomain Histone Readers and Cancer","volume":"429","author":"Jain","year":"2017","journal-title":"J. Mol. Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1007\/s00109-011-0837-0","article-title":"Aberrant epigenetic regulation of bromodomain BRD4 in human colon cancer","volume":"90","author":"Rodriguez","year":"2012","journal-title":"J. Mol. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.phrs.2017.11.015","article-title":"Targeting bromodomain and extraterminal proteins in breast cancer","volume":"129","author":"Sahni","year":"2018","journal-title":"Pharmacol. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1016\/j.fertnstert.2018.02.120","article-title":"Non-coding RNAs: An important regulatory mechanism in pathogenesis of uterine fibroids","volume":"109","author":"Yang","year":"2018","journal-title":"Fertil. Steril."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"4069","DOI":"10.1016\/j.celrep.2019.11.077","article-title":"Integrated Epigenome, Exome, and Transcriptome Analyses Reveal Molecular Subtypes and Homeotic Transformation in Uterine Fibroids","volume":"29","author":"George","year":"2019","journal-title":"Cell Rep."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1038\/s41467-020-14701-6","article-title":"Altered chromatin landscape and enhancer engagement underlie transcriptional dysregulation in MED12 mutant uterine leiomyomas","volume":"11","author":"Moyo","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Yang, Q., Falahati, A., Khosh, A., Mohammed, H., Kang, W., Corachan, A., Bariani, M.V., Boyer, T.G., and Al-Hendy, A. (2022). Targeting Class I Histone Deacetylases in Human Uterine Leiomyosarcoma. Cells, 11.","DOI":"10.3390\/cells11233801"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1038\/nrm.2016.143","article-title":"Functions of bromodomain-containing proteins and their roles in homeostasis and cancer","volume":"18","author":"Fujisawa","year":"2017","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.bcp.2015.12.005","article-title":"Bromodomains: Structure, function and pharmacology of inhibition","volume":"106","author":"Ferri","year":"2016","journal-title":"Biochem. Pharmacol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"12476","DOI":"10.1002\/anie.201705516","article-title":"Beyond the BET Family: Targeting CBP\/p300 with 4-Acyl Pyrroles","volume":"56","author":"Hugle","year":"2017","journal-title":"Angew. Chem. Int. Ed. Engl."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1002\/cmdc.201800738","article-title":"Advancements in the Development of non-BET Bromodomain Chemical Probes","volume":"14","author":"Clegg","year":"2019","journal-title":"ChemMedChem"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e150871","DOI":"10.1172\/jci.insight.150871","article-title":"Inhibition of bromodomain extraterminal histone readers alleviates skin fibrosis in experimental models of scleroderma","volume":"7","author":"Vichaikul","year":"2022","journal-title":"JCI Insight"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"105804","DOI":"10.1016\/j.phrs.2021.105804","article-title":"Selectively targeting individual bromodomain: Drug discovery and molecular mechanisms","volume":"172","author":"Wang","year":"2021","journal-title":"Pharmacol. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1038\/s41594-019-0309-8","article-title":"Bromodomain biology and drug discovery","volume":"26","author":"Zaware","year":"2019","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Ali, M.M., Naz, S., Ashraf, S., Knapp, S., and Ul-Haq, Z. (2023). Epigenetic modulation by targeting bromodomain containing protein 9 (BRD9): Its therapeutic potential and selective inhibition. Int. J. Biol. Macromol., 230.","DOI":"10.1016\/j.ijbiomac.2023.123428"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"11634","DOI":"10.1093\/nar\/gkad907","article-title":"BRD9-mediated control of the TGF-beta\/Activin\/Nodal pathway regulates self-renewal and differentiation of human embryonic stem cells and progression of cancer cells","volume":"51","author":"Wang","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"8372","DOI":"10.1038\/s41467-023-44081-6","article-title":"BRD9 determines the cell fate of hematopoietic stem cells by regulating chromatin state","volume":"14","author":"Xiao","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1410","DOI":"10.1038\/s41556-018-0221-1","article-title":"A non-canonical SWI\/SNF complex is a synthetic lethal target in cancers driven by BAF complex perturbation","volume":"20","author":"Michel","year":"2018","journal-title":"Nat. Cell Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1881","DOI":"10.1038\/s41467-019-09891-7","article-title":"BRD9 defines a SWI\/SNF sub-complex and constitutes a specific vulnerability in malignant rhabdoid tumors","volume":"10","author":"Wang","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Sima, X., He, J., Peng, J., Xu, Y., Zhang, F., and Deng, L. (2019). The genetic alteration spectrum of the SWI\/SNF complex: The oncogenic roles of BRD9 and ACTL6A. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0222305"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Yang, Q., Bariani, M.V., Falahati, A., Khosh, A., Lastra, R.R., Siblini, H., Boyer, T.G., and Al-Hendy, A. (2022). The Functional Role and Regulatory Mechanism of Bromodomain-Containing Protein 9 in Human Uterine Leiomyosarcoma. Cells, 11.","DOI":"10.3390\/cells11142160"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"16330","DOI":"10.1038\/s41598-020-73500-7","article-title":"Cytotoxic activity of bromodomain inhibitor NVS-CECR2-1 on human cancer cells","volume":"10","author":"Park","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Ali, M.M., Ashraf, S., Nure, E.A.M., Qureshi, U., Khan, K.M., and Ul-Haq, Z. (2022). Identification of Selective BRD9 Inhibitor via Integrated Computational Approach. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232113513"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1503","DOI":"10.1158\/1541-7786.MCR-18-1121","article-title":"GSK2801, a BAZ2\/BRD9 Bromodomain Inhibitor, Synergizes with BET Inhibitors to Induce Apoptosis in Triple-Negative Breast Cancer","volume":"17","author":"Bevill","year":"2019","journal-title":"Mol. Cancer Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"4462","DOI":"10.1021\/acs.jmedchem.5b01865","article-title":"Structure-Based Design of an in Vivo Active Selective BRD9 Inhibitor","volume":"59","author":"Martin","year":"2016","journal-title":"J. Med. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Mason, L.D., Chava, S., Reddi, K.K., and Gupta, R. (2021). The BRD9\/7 Inhibitor TP-472 Blocks Melanoma Tumor Growth by Suppressing ECM-Mediated Oncogenic Signaling and Inducing Apoptosis. Cancers, 13.","DOI":"10.3390\/cancers13215516"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1093\/humupd\/dmx032","article-title":"Extracellular matrix in uterine leiomyoma pathogenesis: A potential target for future therapeutics","volume":"24","author":"Islam","year":"2018","journal-title":"Hum. Reprod. Update"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"e475","DOI":"10.1002\/ctm2.475","article-title":"Extracellular matrix and Hippo signaling as therapeutic targets of antifibrotic compounds for uterine fibroids","volume":"11","author":"Islam","year":"2021","journal-title":"Clin. Transl. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2656","DOI":"10.1210\/en.2018-00151","article-title":"Proteomic Characterization of the Extracellular Matrix of Human Uterine Fibroids","volume":"159","author":"Jamaluddin","year":"2018","journal-title":"Endocrinology"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Yang, Q., and Al-Hendy, A. (2023). Update on the Role and Regulatory Mechanism of Extracellular Matrix in the Pathogenesis of Uterine Fibroids. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24065778"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"783289","DOI":"10.1155\/2014\/783289","article-title":"The extracellular matrix contributes to mechanotransduction in uterine fibroids","volume":"2014","author":"Leppert","year":"2014","journal-title":"Obstet. Gynecol. Int."},{"key":"ref_47","first-page":"61","article-title":"Extracellular matrix (ECM) activates beta-catenin signaling in uterine fibroids","volume":"155","author":"Ko","year":"2018","journal-title":"Reproduction"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.matbio.2011.09.001","article-title":"Characterization of tissue biomechanics and mechanical signaling in uterine leiomyoma","volume":"31","author":"Norian","year":"2012","journal-title":"Matrix Biol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.1101\/gad.262766.115","article-title":"RNA N6-methyladenosine methylation in post-transcriptional gene expression regulation","volume":"29","author":"Yue","year":"2015","journal-title":"Genes Dev."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1038\/nchembio.1432","article-title":"A METTL3-METTL14 complex mediates mammalian nuclear RNA N6-adenosine methylation","volume":"10","author":"Liu","year":"2014","journal-title":"Nat. Chem. Biol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.tig.2012.11.003","article-title":"Reversible RNA adenosine methylation in biological regulation","volume":"29","author":"Jia","year":"2013","journal-title":"Trends Genet."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1038\/s41586-020-2854-z","article-title":"Site-specific RNA methylation by a methyltransferase ribozyme","volume":"587","author":"Scheitl","year":"2020","journal-title":"Nature"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Shen, H., Lan, Y., Zhao, Y., Shi, Y., Jin, J., and Xie, W. (2020). The emerging roles of N6-methyladenosine RNA methylation in human cancers. Biomark. Res., 8.","DOI":"10.1186\/s40364-020-00203-6"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.ccr.2012.11.006","article-title":"Regional activation of the cancer genome by long-range epigenetic remodeling","volume":"23","author":"Bert","year":"2013","journal-title":"Cancer Cell"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Garcia, N., Al-Hendy, A., Baracat, E.C., Carvalho, K.C., and Yang, Q. (2020). Targeting Hedgehog Pathway and DNA Methyltransferases in Uterine Leiomyosarcoma Cells. Cells, 10.","DOI":"10.21203\/rs.3.rs-27677\/v1"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2399","DOI":"10.2174\/0929867328666211108105214","article-title":"Histone Modifications and their Role in Epigenetics of Cancer","volume":"29","author":"Zaib","year":"2022","journal-title":"Curr. Med. Chem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1186\/s13148-021-01107-4","article-title":"Current understanding of epigenetics mechanism as a novel target in reducing cancer stem cells resistance","volume":"13","author":"Khorsandi","year":"2021","journal-title":"Clin. Epigenet."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"e1517","DOI":"10.1210\/clinem\/dgz227","article-title":"Activation of beta-Catenin Signaling and its Crosstalk with Estrogen and Histone Deacetylases in Human Uterine Fibroids","volume":"105","author":"Ali","year":"2020","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1097\/PPO.0b013e31803c74cf","article-title":"Utilization of chromatin remodeling agents for lung cancer therapy","volume":"13","author":"Schrump","year":"2007","journal-title":"Cancer J."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Qi, J. (2014). Bromodomain and extraterminal domain inhibitors (BETi) for cancer therapy: Chemical modulation of chromatin structure. Cold Spring Harb. Perspect. Biol., 6.","DOI":"10.1101\/cshperspect.a018663"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"215","DOI":"10.2174\/1874467212666190215112915","article-title":"Targeting Chromatin Remodeling for Cancer Therapy","volume":"12","author":"Kaur","year":"2019","journal-title":"Curr. Mol. Pharmacol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"E1490","DOI":"10.1073\/pnas.1219992110","article-title":"Genome-wide reprogramming of the chromatin landscape underlies endocrine therapy resistance in breast cancer","volume":"110","author":"Magnani","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"560487","DOI":"10.3389\/fonc.2020.560487","article-title":"Small Molecules Targeting HATs, HDACs, and BRDs in Cancer Therapy","volume":"10","author":"Wu","year":"2020","journal-title":"Front. Oncol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"10032","DOI":"10.1158\/0008-5472.CAN-06-2597","article-title":"Bromodomain and histone acetyltransferase domain specificities control mixed lineage leukemia phenotype","volume":"66","author":"Santillan","year":"2006","journal-title":"Cancer Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1038\/nature10509","article-title":"Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia","volume":"478","author":"Dawson","year":"2011","journal-title":"Nature"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"153","DOI":"10.2217\/epi.14.5","article-title":"Targeting the BET family for the treatment of leukemia","volume":"6","author":"Lucas","year":"2014","journal-title":"Epigenomics"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"3670","DOI":"10.4049\/jimmunol.1202838","article-title":"BET protein function is required for inflammation: Brd2 genetic disruption and BET inhibitor JQ1 impair mouse macrophage inflammatory responses","volume":"190","author":"Belkina","year":"2013","journal-title":"J. Immunol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"6915","DOI":"10.18632\/oncotarget.3126","article-title":"JQ1 suppresses tumor growth through downregulating LDHA in ovarian cancer","volume":"6","author":"Qiu","year":"2015","journal-title":"Oncotarget"},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Richter, G.H.S., Hensel, T., Schmidt, O., Saratov, V., von Heyking, K., Becker-Dettling, F., Prexler, C., Yen, H.Y., Steiger, K., and Fulda, S. (2020). Combined Inhibition of Epigenetic Readers and Transcription Initiation Targets the EWS-ETS Transcriptional Program in Ewing Sarcoma. Cancers, 12.","DOI":"10.3390\/cancers12020304"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"643935","DOI":"10.3389\/fgene.2021.643935","article-title":"Gene Signature Associated with Bromodomain Genes Predicts the Prognosis of Kidney Renal Clear Cell Carcinoma","volume":"12","author":"Lu","year":"2021","journal-title":"Front. Genet."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Boyson, S.P., Gao, C., Quinn, K., Boyd, J., Paculova, H., Frietze, S., and Glass, K.C. (2021). Functional Roles of Bromodomain Proteins in Cancer. Cancers, 13.","DOI":"10.3390\/cancers13143606"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1572","DOI":"10.1002\/cam4.4954","article-title":"BRD9 is an essential regulator of glycolysis that creates an epigenetic vulnerability in colon adenocarcinoma","volume":"12","author":"Zhu","year":"2023","journal-title":"Cancer Med."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1807","DOI":"10.1158\/1078-0432.CCR-22-3668","article-title":"BRD9 Degradation Disrupts Ribosome Biogenesis in Multiple Myeloma","volume":"29","author":"Kurata","year":"2023","journal-title":"Clin. Cancer Res."},{"key":"ref_74","first-page":"S79","article-title":"Towards targeted epigenetic therapy of cancer","volume":"14","author":"Magic","year":"2009","journal-title":"J. BUON"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"509","DOI":"10.2174\/156800908785699306","article-title":"Epigenetic aberrations and targeted epigenetic therapy of esophageal cancer","volume":"8","author":"Zhao","year":"2008","journal-title":"Curr. Cancer Drug Targets"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1111\/jcmm.12771","article-title":"Genetic and epigenetic heterogeneity of epithelial ovarian cancer and the clinical implications for molecular targeted therapy","volume":"20","author":"Bai","year":"2016","journal-title":"J. Cell Mol. Med."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"2246","DOI":"10.1039\/C6MD00373G","article-title":"Chemical probes and inhibitors of bromodomains outside the BET family","volume":"7","author":"Moustakim","year":"2016","journal-title":"MedChemComm"},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Kramer, K.F., Moreno, N., Fruhwald, M.C., and Kerl, K. (2017). BRD9 Inhibition, Alone or in Combination with Cytostatic Compounds as a Therapeutic Approach in Rhabdoid Tumors. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18071537"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"2639","DOI":"10.1038\/s41467-020-16443-x","article-title":"The bromodomain containing protein BRD-9 orchestrates RAD51-RAD54 complex formation and regulates homologous recombination-mediated repair","volume":"11","author":"Zhou","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"eabf6045","DOI":"10.1126\/scitranslmed.abf6045","article-title":"Aberrant activation of m6A demethylase FTO renders HIF2alpha(low\/-) clear cell renal cell carcinoma sensitive to BRD9 inhibitors","volume":"13","author":"Zhang","year":"2021","journal-title":"Sci. Transl. Med."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"3364","DOI":"10.21037\/tcr-21-42","article-title":"Targeting BRD9 by I-BRD9 efficiently inhibits growth of acute myeloid leukemia cells","volume":"10","author":"Zhou","year":"2021","journal-title":"Transl. Cancer Res."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"455","DOI":"10.3349\/ymj.2009.50.4.455","article-title":"Epigenetic cross-talk between DNA methylation and histone modifications in human cancers","volume":"50","author":"Kondo","year":"2009","journal-title":"Yonsei Med. J."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1042\/bse0480045","article-title":"Epigenetic markers and their cross-talk","volume":"48","author":"Winter","year":"2010","journal-title":"Essays Biochem."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1083\/jcb.200908151","article-title":"Cross talk between microRNA and epigenetic regulation in adult neurogenesis","volume":"189","author":"Szulwach","year":"2010","journal-title":"J. Cell Biol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1158\/1541-7786.MCR-15-0295","article-title":"HDAC Inhibition for the Treatment of Epithelioid Sarcoma: Novel Cross Talk Between Epigenetic Components","volume":"14","author":"Lopez","year":"2016","journal-title":"Mol. Cancer Res."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"15912","DOI":"10.1038\/s41598-021-95398-5","article-title":"Investigating crosstalk between H3K27 acetylation and H3K4 trimethylation in CRISPR\/dCas-based epigenome editing and gene activation","volume":"11","author":"Zhao","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/j.neuron.2018.06.007","article-title":"Mettl14 Is Essential for Epitranscriptomic Regulation of Striatal Function and Learning","volume":"99","author":"Koranda","year":"2018","journal-title":"Neuron"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.neuron.2017.12.036","article-title":"Epitranscriptomic m6A Regulation of Axon Regeneration in the Adult Mammalian Nervous System","volume":"97","author":"Weng","year":"2018","journal-title":"Neuron"},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Hsu, P.J., Shi, H., and He, C. (2017). Epitranscriptomic influences on development and disease. Genome Biol., 18.","DOI":"10.1186\/s13059-017-1336-6"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"629560","DOI":"10.3389\/fonc.2021.629560","article-title":"YTH Domain Proteins: A Family of m6A Readers in Cancer Progression","volume":"11","author":"Xu","year":"2021","journal-title":"Front. Oncol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"108598","DOI":"10.1016\/j.celrep.2020.108598","article-title":"Ythdf m6A Readers Function Redundantly during Zebrafish Development","volume":"33","author":"Kontur","year":"2020","journal-title":"Cell Rep."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Zhen, D., Wu, Y., Zhang, Y., Chen, K., Song, B., Xu, H., Tang, Y., Wei, Z., and Meng, J. (2020). m6A Reader: Epitranscriptome Target Prediction and Functional Characterization of N6-Methyladenosine (m6A) Readers. Front. Cell Dev. Biol., 8.","DOI":"10.3389\/fcell.2020.00741"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/j.bbagrm.2018.12.008","article-title":"Readers of the m6A epitranscriptomic code","volume":"1862","author":"Berlivet","year":"2019","journal-title":"Biochim. Biophys. Acta Gene Regul. Mech."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"106555","DOI":"10.1016\/j.phrs.2022.106555","article-title":"Glutamate from nerve cells promotes perineural invasion in pancreatic cancer by regulating tumor glycolysis through HK2 mRNA-m6A modification","volume":"187","author":"Li","year":"2023","journal-title":"Pharmacol. Res."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1038\/s41416-021-01581-w","article-title":"Novel evidence for m6A methylation regulators as prognostic biomarkers and FTO as a potential therapeutic target in gastric cancer","volume":"126","author":"Shimura","year":"2022","journal-title":"Br. J. Cancer"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"eaba0647","DOI":"10.1126\/sciadv.aba0647","article-title":"Interplay of m6A and H3K27 trimethylation restrains inflammation during bacterial infection","volume":"6","author":"Wu","year":"2020","journal-title":"Sci. Adv."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.ceb.2020.11.005","article-title":"Chromatin and transcriptional regulation by reversible RNA methylation","volume":"70","author":"Wei","year":"2021","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Omar, M., Laknaur, A., Al-Hendy, A., and Yang, Q. (2019). Myometrial progesterone hyper-responsiveness associated with increased risk of human uterine fibroids. BMC Women\u2019s Health, 19.","DOI":"10.1186\/s12905-019-0795-1"},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Paul, E.N., Burns, G.W., Carpenter, T.J., Grey, J.A., Fazleabas, A.T., and Teixeira, J.M. (2021). Transcriptome Analyses of Myometrium from Fibroid Patients Reveals Phenotypic Differences Compared to Non-Diseased Myometrium. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22073618"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.ymeth.2014.06.008","article-title":"A protocol for RNA methylation differential analysis with MeRIP-Seq data and exomePeak R\/Bioconductor package","volume":"69","author":"Meng","year":"2014","journal-title":"Methods"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1038\/nature23883","article-title":"m6A modulates haematopoietic stem and progenitor cell specification","volume":"549","author":"Zhang","year":"2017","journal-title":"Nature"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1210","DOI":"10.1038\/s41587-022-01243-z","article-title":"m6A RNA modifications are measured at single-base resolution across the mammalian transcriptome","volume":"40","author":"Hu","year":"2022","journal-title":"Nat. Biotechnol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"101677","DOI":"10.1016\/j.xpro.2022.101677","article-title":"Detection of m6A RNA modifications at single-nucleotide resolution using m6A-selective allyl chemical labeling and sequencing","volume":"3","author":"Peng","year":"2022","journal-title":"STAR Protoc."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1126\/science.aad0501","article-title":"Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq","volume":"352","author":"Tirosh","year":"2016","journal-title":"Science"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1097\/01.LAB.0000017499.51216.3E","article-title":"Immortalization of human uterine leiomyoma and myometrial cell lines after induction of telomerase activity: Molecular and phenotypic characteristics","volume":"82","author":"Carney","year":"2002","journal-title":"Lab. Investig."},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Yang, Q., Nair, S., Laknaur, A., Ismail, N., Diamond, M.P., and Al-Hendy, A. (2016). The Polycomb Group Protein EZH2 Impairs DNA Damage Repair Gene Expression in Human Uterine Fibroids. Biol. Reprod., 94.","DOI":"10.1095\/biolreprod.115.134924"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1111\/cpr.12076","article-title":"Role of histone deacetylases in regulation of phenotype of ovine newborn pulmonary arterial smooth muscle cells","volume":"46","author":"Yang","year":"2013","journal-title":"Cell Prolif."},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Love, M.I., Huber, W., and Anders, S. (2014). Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol., 15.","DOI":"10.1186\/s13059-014-0550-8"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1093\/bioinformatics\/btp616","article-title":"edgeR: A Bioconductor package for differential expression analysis of digital gene expression data","volume":"26","author":"Robinson","year":"2010","journal-title":"Bioinformatics"},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Law, C.W., Chen, Y., Shi, W., and Smyth, G.K. (2014). voom: Precision weights unlock linear model analysis tools for RNA-seq read counts. Genome Biol., 15.","DOI":"10.1186\/gb-2014-15-2-r29"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"W90","DOI":"10.1093\/nar\/gkw377","article-title":"Enrichr: A comprehensive gene set enrichment analysis web server 2016 update","volume":"44","author":"Kuleshov","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"e72","DOI":"10.1016\/j.fertnstert.2015.07.219","article-title":"Altered DNA repair genes in human uterine fibroids are epigenetically regulated via EZH2 histone methyltransferase","volume":"104","author":"Yang","year":"2015","journal-title":"Fertil. Steril."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/2\/905\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T13:44:26Z","timestamp":1760103866000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/2\/905"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,11]]},"references-count":112,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2024,1]]}},"alternative-id":["ijms25020905"],"URL":"https:\/\/doi.org\/10.3390\/ijms25020905","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,11]]}}}