TPX2 as a prognostic biomarker and potential therapeutic target for malignant melanoma proliferation and metastasis

Malignant melanoma is an aggressive skin cancer with increasing incidence and poor prognosis after metastasis. Identifying key molecular drivers of melanoma progression is critical for developing novel therapeutic strategies. Therefore, in the present study, differential gene expression analysis was conducted on GSE98394 and The Cancer Genome Atlas-skin cutaneous melanoma datasets using 'limma' package and Gene Expression Profiling Interactive Analysis 2. Consistently dysregulated genes were intersected and subjected to Kaplan-Meier survival and Cox regression analyses. Functional assays, including reverse transcription-quantitative PCR, western blotting, MTT proliferation assay, wound healing, Transwell migration and small interfering (si)RNA-mediated targeting protein for Xklp2 (TPX2) knockdown assays, were performed in A375 and C32 melanoma cells and PIG1 melanocytes. Intersection of the two datasets revealed eight upregulated and five downregulated genes, and high TPX2 expression was significantly associated with short overall survival. TPX2 mRNA and protein levels were markedly higher in A375 cells than in PIG1 controls. <i>TPX2</i> silencing via siRNA reduced aurora kinase A mRNA and protein levels, inhibited cell proliferation and impaired cell migration in wound healing and Transwell assays. Overall, the integrated bioinformatics and experimental analyses identified <i>TPX2</i> as a potent oncogene promoting cell proliferation and migration, at least in part, via upregulation of aurora kinase A in melanoma. In conclusion, TPX2 may constitute a potential prognostic biomarker and therapeutic target for metastatic melanoma.