4.7 Article

IMP-3 Promotes Migration and Invasion of Melanoma Cells by Modulating the Expression of HMGA2 and Predicts Poor Prognosis in Melanoma

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JOURNAL OF INVESTIGATIVE DERMATOLOGY
卷 135, 期 4, 页码 1065-1073

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NATURE PUBLISHING GROUP
DOI: 10.1038/jid.2014.480

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资金

  1. National Science Council of Taiwan [NSC100-2325-B-002-065, NSC 99-2628-B-002-084-MY3, 101-2321-B-002-032]
  2. National Core Facility Program for Biotechnology Grants of National Science Council [NSC 100-2319-B-001-002]
  3. National Taiwan University Hospital [NTUH 101-N1950, NTUH 102-N2274]

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ICE II nnRNA-binding protein 3 (IMP-3) has been reported to be a marker of melanoma progression. However, the mechanisms by which it impacts melanoma are incompletely understood. In this study, we investigate the clinical significance of IMP-3 in melanoma progression and also its underlying mechanisms. We found that IMP-3 expression was much higher in advanced-stage/metastatic melanomas and that it was associated with a poor prognosis (P=0.001). Univariate analysis showed that IMP-3 expression was associated with stage III/1V melanomas (odds ratio =5.40, P=0.031) and the acral lentiginous subtype (odds ratio =3.93, P=0.0034). MeWo cells with overexpression of IMP-3 showed enhanced proliferation and migration and significantly increased tumorigenesis and metastatic ability in nude mice. We further demonstrated that IMP-3 could bind and enhance the stability of the mRNA of high mobility group AT-hook 2 (HMGA2). It was also confirmed that IMP-3 had an important role in melanoma invasion and metastasis through regulating HMGA2 mRNA expression. IMP-3 expression was positively correlated with HMGA2 expression in melanoma cells and also in melanoma tissues. Our results show that IMP-3 expression is a strong prognostic factor for melanoma, especially acral lentiginous melanoma.

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