Department of Dermatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People's Republic of China.
Department of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People's Republic of China.
Arch Dermatol Res. 2019 Jul;311(5):399-410. doi: 10.1007/s00403-019-01909-w. Epub 2019 Apr 17.
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.
先前的研究已经确定神经元导航器 2（NAV2）是几种人类肿瘤中的癌基因。然而，NAV2 基因表达的变化及其在皮肤黑色素瘤发病机制中的作用尚未清楚阐明。进一步研究 NAV2 在皮肤黑色素瘤中的作用可能为这种疾病提供新的机制见解和治疗策略。通过免疫组织化学检测和生物信息学分析，我们发现黑色素瘤组织中 NAV2 的表达上调，与皮肤黑色素瘤的不良预后相关。为了研究 NAV2 对黑色素瘤增殖和侵袭的影响，我们将 shNAV2 和 NAV2-cDNA 转染到黑色素瘤细胞系中。NAV2 的过表达显著促进了黑色素瘤细胞的增殖、迁移和侵袭，而 NAV2 的沉默则有效地抑制了这一过程。通过生物信息学分析、qRT-PCR 和 Western blot 研究了潜在的机制。结果表明，NAV2 通过上皮间质转化驱动黑色素瘤细胞的侵袭，这是由于 SNAI2 通过 GSK-3β/β-catenin 通路的上调所致。这项研究表明，NAV2 可以通过 GSK-3β/β-catenin-SNAI2 通路诱导黑色素瘤的上皮间质转化，从而促进黑色素瘤的增殖和侵袭。我们对 NAV2 相关皮肤黑色素瘤的病理机制的研究结果可能有助于开发黑色素瘤的潜在治疗策略。
