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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: First, the expression level of PARP1 and its correlation with prognosis of melanoma were examined by the TCGA dataset, GEO12391 dataset, and western blot. Then, the differentially expressed genes (DEGs) after PARP1 intervention were screened by microarray slides. Also, Gene Set Enrichment Analysis, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis of DEGs were performed. At the same time, these DEGs were further compared with PARP1-related DEGs in GEO59455, and correlation analysis was performed on the intersection genes to screen PARP1 target genes. Finally, the relationship between PARP1 and its target gene was examined by western blot analysis and reverse transcription-quantitative (RT-q) PCR. CCK8 assay was used to determine the biological role of PARP1 and its target gene in melanoma. The data that support the findings of this study come from the open databases, which are acknowledged at the end of the manuscript. Results: We demonstrated that PARP1 was overexpressed in melanoma and melanoma cell lines, and upregulated expression of PARP1 was associated with higher pathological stages and unfavorable prognosis of melanoma. Five genes, including NFATc2, ITGAX, CYP26B1, SYT17, and VGF, were screened as PARP1 target genes, and NFATc2 was confirmed to be regulated by PARP1. Further CCK8 assay showed that downregulation of PARP1 or NFATc2 expression could inhibit melanoma proliferation. Conclusions: Taken together, this study demonstrated that PARP1 was a prognostic marker and contributed to melanoma proliferation through the regulation of NFATc2.