Karyopherin α 2 promotes proliferation, migration and invasion through activating NF-κB/p65 signaling pathways in melanoma cells

Aims: Melanoma is a fatal malignancy. Karyopherin alpha 2 (KPNA2) plays an important role in many carcinogenesis. This study was aimed to study the role of KPNA2 in cellular functions and molecular mechanisms of melanoma. Main methods: We investigated the expression and prognosis of KPNA2 in melanoma using the GEPIA database (htttp://gepia.cancer-pku.cu/). The effect of KPNA2 on melanoma cells was determined using real-time PCR, western blot, immunofluorescence assay, CCK-8, colony formation, wound healing assay, transwell assay, EMSA, and immunohistochemistry. The influence of KPNA2 on the tumorigenicity of melanoma cells was evaluated in a nude mice model in vivo. Key findings: Our results showed that KPNA2 expression is relatively high in melanoma tissues and cells, and melanoma patients with higher expression of KPNA2 had lower overall survival rate and disease free survival rate. KPNA2 promoted proliferation ability and increased the expression of PCNA, Ki67, and C-MYC in melanoma cells. Further, KPNA2 could promote migration and invasion and increase the expression of MMP2 and MMP9. Mechanism studies showed that KPNA2 activated NF-kappa B/p65 signaling pathways, as evidenced by the nuclear translocation of p65 and increased the expression of COX-2, ICAM-1, iNOS, and MCP1 in melanoma cells. NF-kappa B inhibitor JSH-23 could reverse the pro-tumor effects of KPNA2 on melanoma cells. Moreover, upregulation of KPNA2 facilitated the tumorigenicity of melanoma cells. Significance: KPNA2 promotes proliferation, migration and invasion through enhancing NF-kappa B/p65 signaling pathways in melanoma cells. Our study suggests KPNA2 as a potential therapeutic target for the treatment of melanoma.