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Dysregulation of SOCS protein expression in cancers can be one of the mechanisms that maintain STAT activation, but this mechanism is still poorly understood in oral squamous cell carcinoma (OSCC). Here, we report that SOCS2 protein is significantly downregulated in OSCC patients and its levels are inversely correlated with miR\u2010424\u20105p expression. We identified the SOCS2 protein, which modulates STAT5 activity, as a direct target of miR\u2010424\u20105p. The miR\u2010424\u20105p\u2010induced STAT5 phosphorylation, matrix metalloproteinases (MMPs) expression, and cell migration and invasion were blocked by SOCS2 restoration, suggesting that miR\u2010424\u20105p exhibits its oncogenic activity through negatively regulating SOCS2 levels. Furthermore, miR\u2010424\u20105p expression could be induced by the cytokine IL\u20108 primarily through enhancing STAT5 transcriptional activity rather than NF\u2010\u03baB signaling. Antagomir\u2010mediated inactivation of miR\u2010424\u20105p prevented the IL\u20108\u2010induced cell migration and invasion, indicating that miR\u2010424\u20105p is required for IL\u20108\u2010induced cellular invasiveness. Taken together, these data indicate that STAT5\u2010dependent expression of miR\u2010424\u20105p plays an important role in mediating IL\u20108\/STAT5\/SOCS2 feedback loop, and scavenging miR\u2010424\u20105p function using antagomir may have therapeutic potential for the treatment of OSCC.<\/jats:p>","DOI":"10.1016\/j.molonc.2016.03.001","type":"journal-article","created":{"date-parts":[[2016,3,22]],"date-time":"2016-03-22T12:23:25Z","timestamp":1458649405000},"page":"895-909","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":62,"title":["IL\u20108 induces miR\u2010424\u20105p expression and modulates SOCS2\/STAT5 signaling pathway in oral squamous cell carcinoma"],"prefix":"10.1002","volume":"10","author":[{"given":"Hsuan-Yu","family":"Peng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shih-Sheng","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenn-Ren","family":"Hsiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Hsiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan-Ming","family":"Hsu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guan-Hsun","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-Min","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jang-Yang","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiow-Lian Catherine","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shine-Gwo","family":"Shiah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,3,22]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1206923"},{"key":"e_1_2_10_3_1","first-page":"1217","article-title":"High incidence of p53 alterations (mutation, deletion, overexpression) in head and neck primary tumors and metastases; absence of correlation with clinical outcome. 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