Abstract

BACKGROUND: Melanoma of the skin can be associated with early metastases and poor prognosis. This study aimed to identify microRNAs (miRNAs) and target genes associated with prognosis in melanoma using bioinformatics analysis.

MATERIAL AND METHODS: The Gene Expression Omnibus (GEO) database identified the microarray dataset GSE20994. Differentially expressed miRNAs (DE-miRNAs) were first identified using R language software and validated by GEO2R. Potential target genes of DE-miRNAs were screened, and their targets and prognostic role were evaluated in the miRTarBase database. Pathway enrichment and functional annotation analysis for target genes were established using the DAVID database. miRNA-hub gene networks and protein-protein interaction (PPI) networks were constructed and visualized using the STRING database and Cytoscape. Kaplan-Meier survival curves were constructed using transcriptome and survival data from the UALCAN web tool.

RESULTS: There were 132 upregulated and 134 down-regulated DE-miRNAs identified from human melanoma samples. From the top three upregulated miRNAs, there were 580 potential predicted target genes, and from the top three down-regulated miRNAs, there 543 potential predicted target genes. miR-300 was upregulated, and miR-629 was down-regulated in melanoma. Two pivotal bub genes, TP53 and GAPDH, were identified in the PPI network. Five out of ten hub genes were modulated by upregulated miR-580, and five by miR-629. Increased mRNA expression of DAPK2 was associated with increased OS, and increased mRNA expression of SKCM, TECPR2, and ZNF781 were associated with reduced OS.

CONCLUSIONS: Bioinformatics analysis identified miRNAs and target genes associated with melanoma that may represent potential prognostic and therapeutic biomarkers.

Keywords: Computational Biology, Melanoma, MicroRNAs, Prognosis, Databases, Genetic, Gene Expression Profiling, gene ontology, Gene Regulatory Networks, Protein Interaction Maps, RNA, Messenger, Skin Neoplasms, Software, transcriptome