PARP1 Is a Prognostic Marker and Targets NFATc2 to Promote Carcinogenesis in Melanoma

Background: Melanoma is the most lethal skin tumor. PARP1 plays an oncogenic role in tumors, but the mechanism of PARP1 in melanoma remains unclear. Explicating the functional mechanism of PARP1 might highlight new targets for improving the survival rate of melanoma patients. Methods: The expression level of PARP1 and its correlation with prognosis of melanoma were examined using the TCGA dataset, the GEO12391 dataset, and western blot analysis. The differentially expressed genes (DEGs) following PARP1 intervention were identified via microarray analyses. GSEA, GO, and KEGG pathway enrichment analyses of the DEGs were performed. Theses DEGs were also compared with PARP1-related DEGs in the GEO59455 dataset and correlation analyses were performed to identify the intersection of the two gene sets to identify PARP1 target genes. The regulatory relationship between PARP1 and its target gene NFATc2 was examined by Western blot analysis and RT-qPCR. A CCK8 assay was used to determine the biological role of PARP1 and its target, NFATc2, in melanoma. Results: We demonstrated that PARP1 was overexpressed in both melanoma tissues and melanoma cell lines, and that upregulated expression of PARP1 was associated with higher pathological stages and unfavorable prognosis of melanoma. Five genes (NFATc2, ITGAX, CYP26B1, SYT17, and VGF) were identified as PARP1 target genes, and NFATc2 expression was confirmed to be regulated by PARP1. A CCK8 assay showed that by down-regulating expression of PARP1 or NFATc2 that melanoma proliferation was inhibited. Conclusions: Taken together, the results of this study demonstrated that PARP1 expression is a prognostic marker and contributes to melanoma proliferation through the regulation of NFATc2.