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In a previous study, we found elevated XIST (X\u2010inactive specific transcript) levels in fibroids, which sponged miR\u201029c and miR\u2010200c, leading to the overexpression of their target genes. This study aimed to assess the therapeutic potential of XIST downregulation in fibroid treatment. Ovariectomized SCID (severe combined immunodeficiency) mice were implanted with fibroid tumors transduced with XIST siRNA or a control via lentivirus. After 1\u2009month, animals were sacrificed and the xenografts were removed for further analysis. XIST knockdown reduced tumor weight by 15% and increased miR\u201029c and miR\u2010200c expression by 3.9\u2010fold and 2.2\u2010fold, respectively. The mRNA expression of miR\u201029c targets (\n                    <jats:italic>COL3A1<\/jats:italic>\n                    ,\n                    <jats:italic>TGF\u2010\u03b23<\/jats:italic>\n                    ,\n                    <jats:italic>CDK2<\/jats:italic>\n                    ,\n                    <jats:italic>SPARC<\/jats:italic>\n                    ) and miR\u2010200c targets (\n                    <jats:italic>CDK2<\/jats:italic>\n                    ,\n                    <jats:italic>FN1<\/jats:italic>\n                    ,\n                    <jats:italic>TDO2<\/jats:italic>\n                    ), as well as\n                    <jats:italic>PRL<\/jats:italic>\n                    ,\n                    <jats:italic>E2F1<\/jats:italic>\n                    , and\n                    <jats:italic>EZH2<\/jats:italic>\n                    , was significantly decreased. Protein abundance of collagen, COL3A1, FN1, CDK2, SPARC, and EZH2 was also reduced. IHC analysis of xenograft sections using the markers of Ki67 for cell proliferation and cleaved caspase 3 for apoptosis showed decreased cell proliferation and no changes in apoptosis in the XIST knockdown xenografts. This analysis also revealed decreased collagen and E2F1 staining nuclei in the XIST knockdown xenografts. These results indicate that downregulation of XIST in fibroids has beneficial therapeutic effects, by reducing tumor growth and the expression of genes involved in cell proliferation, inflammation, and extracellular matrix regulation.\n                  <\/jats:p>","DOI":"10.1096\/fj.202401982r","type":"journal-article","created":{"date-parts":[[2024,10,30]],"date-time":"2024-10-30T12:37:11Z","timestamp":1730291831000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["The in\u00a0vivo effects of knockdown of long non\u2010coding\n                    <scp>RNA XIST<\/scp>\n                    on fibroid growth and gene expression"],"prefix":"10.1096","volume":"38","author":[{"given":"Tsai\u2010Der","family":"Chuang","sequence":"first","affiliation":[{"name":"The Lundquist Institute for Biomedical Innovation  Torrance California 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