{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T01:36:48Z","timestamp":1789522608190,"version":"build-2803163510"},"reference-count":98,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2024,8,28]],"date-time":"2024-08-28T00:00:00Z","timestamp":1724803200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institutes of Health (NIH)","award":["R01 HD106285"],"award-info":[{"award-number":["R01 HD106285"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Uterine leiomyosarcoma (uLMS) is the most common type of uterine sarcoma, associated with poor prognosis, high rates of recurrence, and metastasis. Currently, the molecular mechanism of the origin and development of uLMS is limited. Bromodomain and extra-terminal (BET) proteins are involved in both physiological and pathological events. However, the role of BET proteins in the pathogenesis of uLMS is unknown. Here, we show for the first time that BET protein family members, BRD2, BRD3, and BRD4, are aberrantly overexpressed in uLMS tissues compared to the myometrium, with a significant change by histochemical scoring assessment. Furthermore, inhibiting BET proteins with their small, potent inhibitors (JQ1 and I-BET 762) significantly inhibited the uLMS proliferation dose-dependently via cell cycle arrest. Notably, RNA-sequencing analysis revealed that the inhibition of BET proteins with JQ1 and I-BET 762 altered several critical pathways, including the hedgehog pathway, EMT, and transcription factor-driven pathways in uLMS. In addition, the targeted inhibition of BET proteins altered several other epigenetic regulators, including DNA methylases, histone modification, and m6A regulators. The connections between BET proteins and crucial biological pathways provide a fundamental structure to better understand uterine diseases, particularly uLMS pathogenesis. Accordingly, targeting the vulnerable epigenome may provide an additional regulatory mechanism for uterine cancer treatment.<\/jats:p>","DOI":"10.3390\/cells13171443","type":"journal-article","created":{"date-parts":[[2024,8,28]],"date-time":"2024-08-28T05:34:49Z","timestamp":1724823289000},"page":"1443","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Unraveling the Role of Bromodomain and Extra-Terminal Proteins in Human Uterine Leiomyosarcoma"],"prefix":"10.3390","volume":"13","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, Chicago, IL 60637, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Falahati","sequence":"additional","affiliation":[{"name":"Poundbury Cancer Institute for Personalised Medicine, Dorchester DT1 3BJ, UK"},{"name":"DNA GTx LAB, Dubai Healthcare City, Dubai 505262, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3267-4280","authenticated-orcid":false,"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"}]},{"given":"Ricardo R.","family":"Lastra","sequence":"additional","affiliation":[{"name":"Department of Pathology, 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, Chicago, IL 60637, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.ygyno.2009.09.023","article-title":"Uterine sarcomas: A review","volume":"116","author":"Prat","year":"2010","journal-title":"Gynecol. 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