In silico analysis of microRNA-gene interactions involved in melanoma pathogenesisoma pathogenesis

Abstract

Relevance: Cutaneous melanoma is one of the most aggressive malignancies, in which mutations in the BRAF, NRAS, and KIT genes play a key role by activating the MAPK/ERK and RAS-RAF signaling pathways. In recent years, increasing attention has been given to the role of microRNAs (miRNAs) in regulating these signaling pathways. miRNAs can modulate the expression of oncogenes and tumor suppressor genes, influencing the growth, invasion, and therapy resistance of melanoma cells.

Aim of the study: To identify the key “miRNA-gene” interaction pairs involved in melanoma pathogenesis and to evaluate their role in regulating major signaling cascades.

Methods: Data from open-access databases NCBI and PubMed were used for analysis. Interactions between miRNAs and genes were investigated using the DIANA Tools bioinformatics platform, where interaction scores (Score) were calculated to reflect binding probability. Genes involved in the regulation of the cell cycle, apoptosis, and signal transduction were analyzed, as well as 30 of the most significant miRNAs associated with melanomagenesis.

Results: Fifteen key genes (BRAF, NRAS, KRAS, KIT, NF1, MAP3K1, etc.) and 30 miRNAs modulating their expression were identified. The strongest interaction scores (Score ≥ 0.99) were found for the pairs BRAF-miR-5011-5p, KIT-miR-5011-5p, NRAS-miR-4775, NF1-miR-3658, and HRH2-miR-4443. The study showed that miRNAs regulate the MAPK, PI3K/AKT, and RAS pathways, thereby affecting cell proliferation and apoptosis.

Conclusion: The study identified new potential regulatory “miRNA-target gene” pairs associated with melanoma and demonstrated that post-transcriptional regulation plays a crucial role in melanoma pathogenesis. The findings suggest that specific miRNAs may serve as promising diagnostic biomarkers and therapeutic targets for melanoma.