{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T03:03:01Z","timestamp":1785294181315,"version":"3.55.0"},"reference-count":44,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2013,3,9]],"date-time":"2013-03-09T00:00:00Z","timestamp":1362787200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2013,8,15]]},"abstract":"<jats:p>Metastasis is the major factor affecting patient survival in ovarian cancer. However, its molecular mechanisms remain unclear. Our study used isogenic pairs of low\u2010 and high\u2010invasive ovarian cancer cell lines to demonstrate the downregulation of miRNA\u2010138 in the highly invasive cells, and its functioning as an inhibitor of cell migration and invasion. An orthotopic xenograft mouse model further demonstrated that the expression of miRNA\u2010138 inhibited ovarian cancer metastasis to other organs. Results indicated that miR\u2010138 directly targeted SRY\u2010related high mobility group box 4 (SOX4) and hypoxia\u2010inducible factor\u20101\u03b1 (HIF\u20101\u03b1), and overexpression of SOX4 and HIF\u20101\u03b1 effectively reversed the miR\u2010138\u2010mediated suppression of cell invasion. Epidermal growth factor receptor acted as the downstream molecule of SOX4 by way of direct transcriptional control, whereas Slug was the downstream molecule of HIF\u20101\u03b1 by way of proteasome\u2010mediated degradation. Analysis of human ovarian tumors further revealed downregulation of miR\u2010138 and upregulation of SOX4 in late\u2010stage tumors. Patients with miR\u2010138<jats:sup>low<\/jats:sup>\/SOX<jats:sup>high<\/jats:sup> signature are predominant in late stage and tend to have malignant phenotypes including lymph nodes metastasis, larger ascites volume and higher tumor grade. Our study demonstrates the role and clinical relevance of miR\u2010138 in ovarian cancer cell invasion and metastasis, providing a potential therapeutic strategy for suppression of ovarian cancer metastasis by targeting SOX4 and HIF\u20101\u03b1 pathways.<\/jats:p>","DOI":"10.1002\/ijc.28086","type":"journal-article","created":{"date-parts":[[2013,2,6]],"date-time":"2013-02-06T13:39:11Z","timestamp":1360157951000},"page":"867-878","source":"Crossref","is-referenced-by-count":200,"title":["MicroRNA\u2010138 suppresses ovarian cancer cell invasion and metastasis by targeting SOX4 and HIF\u20101\u03b1"],"prefix":"10.1002","volume":"133","author":[{"given":"Yu\u2010Ming","family":"Yeh","sequence":"first","affiliation":[{"name":"Institute of Molecular and Genomic Medicine, National Health Research Institute Zhunan, Miaoli Taiwan Republic of China"},{"name":"Institute of Molecular Medicine National Tsing Hua University Hsinchu Taiwan Republic of 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