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Fibroid-derived exosomes (Fib-EXO) expressed the canonical extracellular vesicle markers CD81 and CD63, and their size distribution (30\u2013200\u00a0nm) was consistent with exosomal vesicles. The RNA cargo of Fib-EXO generally reflected that of its tissue of origin, although selective enrichment of specific transcripts, such as piR-1398740 and piR-333378, suggested active loading mechanisms. Long RNA sequencing identified differential expression of protein-coding genes and long noncoding RNAs (lncRNAs) involved in RNA binding, cytoplasmic translation, exosome pathways, and PI3K\/AKT and focal adhesion signaling. qPCR validation confirmed increased IGF2, HOXA10, and decreased IGFBP6 mRNA expression in Fib-EXO. Among lncRNAs, MSC-AS1, PART1, and H19 were overexpressed in Fib-EXO. Small RNA sequencing revealed differential expression of multiple small noncoding RNA classes, including Piwi-interacting RNAs, miRNAs, snRNAs, snoRNAs, and tRNAs. KEGG analysis showed that miRNAs were primarily associated with PI3K\/AKT signaling, proteoglycans in cancer, interleukin signaling, and transcriptional regulation. Functionally, Fib-EXO were internalized by myometrial cells and promoted their proliferation with no effects on apoptosis. Furthermore, Fib-EXO enhanced angiogenesis in human umbilical vein endothelial cells. Fib-EXO increased the expression of vimentin, EZH2, DNMT1, TGF-\u03b23, and c-MYC, and phosphorylated p65 protein, reduced COL1A1 and COL3A1 expression, and decreased miR-133a, miR-29, and miR-200c while increasing miR-21 in cultured myometrial smooth muscle cells, mirroring changes observed in fibroids. These findings indicate that Fib-EXO reprogram myometrial cells toward a fibroid-like phenotype characterized by increased proliferation, inflammation, and fibrotic features, thus contributing to fibroid propagation.<\/jats:p>","DOI":"10.1042\/cs20250814","type":"journal-article","created":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T16:32:26Z","timestamp":1776702746000},"page":"805-824","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Transcriptomic and functional analysis of fibroid extracellular vesicles"],"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":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abigail","family":"Wiseman","sequence":"additional","affiliation":[{"name":"1The Lundquist Institute for Biomedical Innovation, Torrance, CA, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriela","family":"Alfaro","sequence":"additional","affiliation":[{"name":"1The Lundquist Institute for Biomedical Innovation, Torrance, CA, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shawn","family":"Rysling","sequence":"additional","affiliation":[{"name":"1The Lundquist Institute for Biomedical Innovation, Torrance, CA, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nhu","family":"Ton","sequence":"additional","affiliation":[{"name":"1The Lundquist Institute for Biomedical Innovation, Torrance, CA, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Baghdasarian","sequence":"additional","affiliation":[{"name":"2Department of Obstetrics and Gynecology, Harbor-UCLA Medical Center, Torrance, CA, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","published-online":{"date-parts":[[2026,5,5]]},"reference":[{"key":"2026050505213831900_B1","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1093\/humupd\/dmt058","article-title":"Proceedings from the Third National Institutes of Health International Congress on Advances in Uterine Leiomyoma Research: comprehensive review, conference summary and future recommendations","volume":"20","author":"Segars","year":"2014","journal-title":"Hum. 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