Active natural compounds perturb the melanoma risk-gene network
Cutaneous melanoma is an aggressive type of skin cancer with a complex genetic landscape caused by the malignant transformation of melanocytes. The study aimed at providing an in-silico network model based on the systematic profiling of the melanoma-associated genes considering germline mutations, somatic mutations, and genome-wide association studies (GWAS) signals (collectively melanoma risk genes). A protein-protein interaction network (melanoma risk network) was constructed using the melanoma risk genes to describe the functional landscape in which the melanoma genes operate within the cellular milieu. A significant portion of the melanoma risk network showed differential expression when SK-MEL-28 human melanoma cells were exposed to the phytochemicals harmine and berberine chloride reinforcing the hypothesis that network modelling may represent an alternative screening approach to prioritize potentially active compounds. Overall design: SK-MEL-28 human melanoma cells were treated with harmine and berberine chloride and differential gene expression following RNAseq was calculated in comparison with DMSO treated controls. All treatments were analysed using experimental triplicates. The genes with significant alteration in expression following drug treatment, were mapped onto an in-silico model of melanoma obtained using protein network analysis of melanoma risk genes. This led to the identification of the portions of the model affected/modulated by the treatment.