IMP-3 promotes migration and invasion of melanoma cells by modulating the expression of HMGA2 and predicts poor prognosis in 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.
Department of Dermatology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
Yi-Shuan
YS
Sheen
Department of Dermatology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
Yi-Hua
YH
Liao
Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan; Department of Surgery, National Taiwan University Hospital Hsin-Chu Branch, Hisn-Chu, Taiwan.
Ming-Hsien
MH
Lin
Department of Life Science, Institute of Zoology, College of Life Science, National Taiwan University, Taipei, Taiwan.
Chia-Ying
CY
Chu
Department of Dermatology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
Bing-Ying
BY
Ho
Department of Dermatology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
Meng-Chen
MC
Hsieh
Department of Dermatology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
Pin-Chun
PC
Chen
Institute of Biochemical Sciences, College of Life Science, National Taiwan University, Taipei, Taiwan.
Shih-Ting
ST
Cha
Department of Pathology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
Yung-Ming
YM
Jeng
Graduate Institute of Oral Biology, School of Dentistry, National Taiwan University, Taipei, Taiwan.
Cheng-Chi
CC
Chang
Department of Dermatology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
Hsien-Ching
HC
Chiu
Department of Dermatology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
Shiou-Hwa
SH
Jee
Institute of Biochemical Sciences, College of Life Science, National Taiwan University, Taipei, Taiwan.
Min-Liang
ML
Kuo
Department of Dermatology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan. Electronic address: chiayu@ntu.edu.tw.
Chia-Yu
CY
Chu
D014408:Biomarkers, Tumor; D045744:Cell Line, Tumor; D002465:Cell Movement; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D025743:HMGA2 Protein / Q000378:metabolism*; D006801:Humans; D008545:Melanoma / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D016017:Odds Ratio; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D016601:RNA-Binding Proteins / Q000378:metabolism*; D012878:Skin Neoplasms / Q000378:metabolism*; D000096142:Cutaneous Malignant Melanoma
D014408:Biomarkers, Tumor; D025743:HMGA2 Protein; C498780:IGF2BP3 protein, human; D016601:RNA-Binding Proteins