{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T14:18:09Z","timestamp":1784557089302,"version":"3.55.0"},"reference-count":68,"publisher":"Bioscientifica","issue":"4","license":[{"start":{"date-parts":[[2012,6,8]],"date-time":"2012-06-08T00:00:00Z","timestamp":1339113600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/www.endocrinology.org\/journals\/reuselicence\/"}],"content-domain":{"domain":["erc.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2012,8]]},"abstract":"<jats:p>\n                    MicroRNA-200c (miR-200c) through repression of specific target genes has been associated with cellular transition, tumorigenesis, and tissue fibrosis. We explored the expression and functional aspects of miR-200c in genesis of leiomyomas (LYO), benign uterine tumors with fibrotic characteristic. Using LYO and matched myometrium (MYO;\n                    <jats:italic>n<\/jats:italic>\n                    =76) from untreated and from patients exposed to hormonal therapies (GNRH agonist (GNRHa), Depo-Provera, and oral contraceptives), we found that miR-200c was expressed at significantly lower levels (\n                    <jats:italic>P<\/jats:italic>\n                    &lt;0.05) in LYO as compared with MYO. These levels were lower in LYO from African Americans as compared with Caucasians, patients experiencing abnormal uterine bleeding and those exposed to GNRHa therapy. Gain-of-function of miR-200c in isolated leiomyoma smooth muscle cells (LSMCs), myometrial smooth muscle cells (MSMCs), and leiomyosarcoma cell line (SKLM-S1) repressed\n                    <jats:italic>ZEB1\/ZEB2<\/jats:italic>\n                    mRNAs and proteins, with concurrent increase in E-cadherin (\n                    <jats:italic>CDH1<\/jats:italic>\n                    ) and reduction in vimentin expression, phenotypic alteration, and inhibition of MSMC and LSMC proliferations. We further validated\n                    <jats:italic>TIMP2, FBLN5<\/jats:italic>\n                    , and\n                    <jats:italic>VEGFA<\/jats:italic>\n                    as direct targets of miR-200c through interaction with their respective 3\u2032 UTRs, and other genes as determined by microarray analysis. At tissue levels, LYO expressed lower levels of\n                    <jats:italic>TIMP2<\/jats:italic>\n                    and\n                    <jats:italic>FBLN5<\/jats:italic>\n                    mRNAs but increased protein expressions, which to some extent altered due to hormonal exposure. Given the regulatory functions of\n                    <jats:italic>ZEBs, VEGFA, FBLN5<\/jats:italic>\n                    , and\n                    <jats:italic>TIMP2<\/jats:italic>\n                    on cellular activities that promote cellular transition, angiogenesis, and matrix remodeling, we concluded that altered expression of miR-200c may have a significant impact on the outcome of LYO growth, maintenance of their mesenchymal and fibrotic characteristics, and possibly their associated symptoms.\n                  <\/jats:p>","DOI":"10.1530\/erc-12-0007","type":"journal-article","created":{"date-parts":[[2012,6,8]],"date-time":"2012-06-08T23:41:04Z","timestamp":1339198864000},"page":"541-556","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":79,"title":["miR-200c is aberrantly expressed in leiomyomas in an ethnic-dependent manner and targets ZEBs, VEGFA, TIMP2, and FBLN5"],"prefix":"10.1530","volume":"19","author":[{"given":"Tsai-Der","family":"Chuang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harekrushna","family":"Panda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoping","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nasser","family":"Chegini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"issue":"7209","key":"1_31634312","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1038\/nature07242","volume":"455","author":"Baek","year":"2008","journal-title":"Nature; Physical Science 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