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Large RNA next-generation sequencing revealed that 680C91 induced broad transcriptomic alterations, with enrichment of pathways related to the extracellular space, RNA processing, PI3K\/AKT signaling, and calcium signaling. Small RNA sequencing identified enrichment of pathways associated with PI3K\/AKT signaling, proteoglycans in cancer, and interleukin signaling. Key differentially expressed genes were validated in xenografts and fibroid explants. Treatment with 680C91 significantly reduced the mRNA expression of VDR, MMP11, MMP14, COL11A1, CBX4, LINC02568, LINC01310, LINC02544, and LINC02182, while increasing miR-584-5p expression. These changes were consistently observed in fibroid explants treated with 680C91 for 48\u00a0h. Corresponding decreases in protein levels of COL11A1, VDR, CBX4, MMP11, and MMP14 were also detected. Additionally, 680C91 inhibited AKT phosphorylation and reduced \u03b1-smooth muscle actin and vimentin expression. Importantly, all validated transcripts displayed expression patterns opposite to those observed in fibroid tissues compared with matched myometrium, with more pronounced effects in MED12-mutated tumors. These preclinical findings support TDO2 inhibition as a potential therapeutic strategy for uterine fibroids.<\/jats:p>","DOI":"10.1042\/cs20260395","type":"journal-article","created":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T14:29:52Z","timestamp":1778509792000},"page":"1099-1117","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["<i>In vivo<\/i>\n                    inhibition of TDO2 in fibroids results in widespread alteration in the tumor transcriptome"],"prefix":"10.1042","volume":"140","author":[{"given":"Tsai-Der","family":"Chuang","sequence":"first","affiliation":[{"name":"1The Lundquist Institute for Biomedical Innovation, Torrance, CA, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abigail","family":"Wiseman","sequence":"additional","affiliation":[{"name":"1The Lundquist Institute for Biomedical Innovation, Torrance, CA, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela","family":"Alfaro","sequence":"additional","affiliation":[{"name":"1The Lundquist Institute for Biomedical Innovation, Torrance, CA, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sayna","family":"Pejouhesh Jahromi","sequence":"additional","affiliation":[{"name":"1The Lundquist Institute for Biomedical Innovation, Torrance, CA, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sepideh","family":"Pejouhesh Jahromi","sequence":"additional","affiliation":[{"name":"1The Lundquist Institute for Biomedical Innovation, Torrance, CA, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Baghdasarian","sequence":"additional","affiliation":[{"name":"2Department of Obstetrics and Gynecology, Harbor-UCLA Medical Center, Torrance, CA, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4996-5762","authenticated-orcid":false,"given":"Omid","family":"Khorram","sequence":"additional","affiliation":[{"name":"1The Lundquist Institute for Biomedical Innovation, Torrance, CA, U.S.A."},{"name":"2Department of Obstetrics and Gynecology, Harbor-UCLA Medical Center, Torrance, CA, U.S.A."},{"name":"3Department of Obstetrics and Gynecology, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2026,5,26]]},"reference":[{"key":"2026052601110761800_B1","doi-asserted-by":"publisher","first-page":"1029","DOI":"10.1002\/ijgo.70527","article-title":"The epidemiology and pathogenesis of uterine fibroids","volume":"171","author":"Munro","year":"2025","journal-title":"Int. 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