Upregulation of miR-4286 and miR-146a-5p in Metastatic Melanoma, Revealed by Multiplex Expression Analysis

Metastatic melanoma is an extremely aggressive malignancy with limited therapeutic options, despite advances in targeted and immunotherapy. MicroRNAs are key post-transcriptional regulators of gene expression and play a critical role in tumor adaptation, invasion, and metastasis. The aim of our study was to identify dysregulated miRNAs which may serve as novel biomarkers and therapeutic targets.

The study was conducted on FFPE samples from metastatic melanoma (n = 15), compared to healthy skin tissue (n = 6). BRAF V600E/Ec mutation status was established by Real-Time qPCR. Expression miRNA analysis was performed, using digital counting of 827 miRNAs on the NanoString platform, with data normalization and fold change calculations.

Following normalization and quality control metrics, 58 differentially expressed miRNAs were identified in BRAFwt melanoma samples: 6 overexpressed and 52 inderexpressed miRNAs. In BRAFmut melanoma, 37 microRNAs were differentially expressed: 11 overexpressed and 26 underexpressed. Four miRNAs showed elevated expression in both melanoma groups. Among them, miR-146a-5p and miR-4286 demonstrated the highest elevation, especially in BRAFmut tumors. We focused further on their targeted genes.

This study demonstrates significant alterations in the miRNA expression profile in metastatic melanoma and highlights the potential of miR-146a-5p and miR-4286 as key regulators of tumor biology.