NAV2 facilitates invasion of cutaneous melanoma cells by targeting SNAI2 through the GSK-3β/β-catenin pathway
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Previous studies have identified neuron navigator 2(NAV2) as an oncogene in several human tumors. However, the NAV2 gene expression changes and its role in the pathogenesis of cutaneous melanoma have not been clearly illustrated. Further investigations of NAV2 in cutaneous melanoma may provide new mechanistic insight and treatment strategy for this disease. Through immunohistochemistry assay and bioinformatics analysis, we found that melanoma tissues showed an upregulated expression of NAV2 which correlated with poor prognosis of cutaneous melanoma. To investigate the effect of NAV2 on the proliferation and invasion of melanoma, shNAV2 and NAV2-cDNA were transfected into melanoma cell lines. NAV2 overexpression significantly promoted melanoma cell proliferation, migration and invasion, while NAV2 silencing effectively inhibited this process. The potential underlying mechanisms were investigated using bioinformatics analysis, qRT-PCR, and western blot. Results showed that NAV2-mediated invasion of melanoma cells was driven by enhanced epithelial–mesenchymal transition, which was resulted from SNAI2 upregulation via the GSK-3β/β-catenin pathway. This study suggested that NAV2 could induce melanoma proliferation and invasion by epithelial–mesenchymal transition through the GSK-3β/β-catenin-SNAI2 pathway. Our findings on the pathological mechanisms of NAV2-associated cutaneous melanoma may contribute to the development of potential therapeutic strategy for melanoma.
KeywordsNAV2 Melanoma SNAI2 Epithelial-to-mesenchymal transition Bioinformatics analysis
Skin cutaneous melanoma
Snail homolog 2
Kyoto encyclopedia of genes and genomes
We acknowledge all the colleagues who participated in this study.
This work was supported by the National Natural Science Foundation of China (No.81472000).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
All procedures performed in this study involving human participants were approved by the Ethics Committee of Tongji hospital and in accordance with the declaration of Helsinki.
Informed consent was obtained from all individual participants included in the study.
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