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

TL;DR

This study identifies miR-4286 and miR-146a-5p as overexpressed microRNAs in metastatic melanoma, suggesting their potential as biomarkers or therapeutic targets.

Contribution

The study reveals novel miRNA biomarkers in metastatic melanoma, specifically miR-4286 and miR-146a-5p, which are significantly upregulated in both BRAF wild-type and mutant tumors.

Findings

58 differentially expressed miRNAs were identified in BRAF wild-type melanoma samples.

37 differentially expressed miRNAs were found in BRAF mutant melanoma samples.

miR-146a-5p and miR-4286 were the most elevated miRNAs in both melanoma groups.

Abstract

Background: 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. Materials and Methods: 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. Results: 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. Conclusion: 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.

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