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

2014; Elsevier BV; Volume: 135; Issue: 4 Linguagem: Inglês

10.1038/jid.2014.480

1523-1747

Yi‐Shuan Sheen, Yi‐Hua Liao, Ming‐Hsien Lin, Chia‐Ying Chu, Bing‐Ying Ho, Meng-Chen Hsieh, Pin‐Chun Chen, Shih-Ting Cha, Yung‐Ming Jeng, Cheng-Chi Chang, Hsien‐Ching Chiu, Shiou‐Hwa Jee, Min‐Liang Kuo, Chia‐Yu Chu,

interferon and immune responses

IGF II mRNA-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/IV 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. IGF II mRNA-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/IV 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. acral lentiginous melanoma high mobility group AT-hook 2 IGF II mRNA-binding protein 3 IMP-3 overexpressing MeWo cells MeWo cells with vector clone leucine zipper protein 4/CT-8/HOM-TES-85 transforming growth factor-β2