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 α 2 plays an important role in many carcinogenesis. This study was aimed to study the role of in cellular functions and molecular mechanisms of melanoma. MAIN METHODS:We investigated the expression and prognosis of Kduanyu15352 in melanoma using the GEPIA database (http://gepia.cancer-pku.cn/). The effect of Kduanyu15352 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 Kduanyu15352 on the tumorigenicity of melanoma cells was evaluated in a nude mice model in vivo. KEY FINDINGS:Our results showed that Kduanyu15352 expression is relatively high in melanoma tissues and cells, and melanoma patients with higher expression of Kduanyu15352 had lower overall survival rate and disease free survival rate. Kduanyu15352 promoted proliferation ability and increased the expression of PCNA, Ki67, and C-MYC in melanoma cells. Further, Kduanyu15352 could promote migration and invasion and increase the expression of MMP2 and MMP9. Mechanism studies showed that Kduanyu15352 activated NF-κB/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-κB inhibitor JSH-23 could reverse the pro-tumor effects of Kduanyu15352 on melanoma cells. Moreover, upregulation of Kduanyu15352 facilitated the tumorigenicity of melanoma promotes proliferation, migration and invasion through enhancing NF-κB/p65 signaling pathways in melanoma cells. Our study suggests Kduanyu15352 as a potential therapeutic target for the treatment of melanoma.

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