Decoding Post-Transcriptional Networks Governing the Melanoma Extracellular Matrix

The extracellular matrix (ECM) is a key determinant of melanoma progression, regulating tumor cell behavior through biochemical and biomechanical cues. MicroRNAs (miRNAs) have emerged as critical post-transcriptional regulators of gene expression and are increasingly recognized as important modulators of ECM remodeling in cancer. This review summarizes current evidence on miRNA-mediated regulation of ECM components and ECM-associated pathways in melanoma (matrix-miRNAs). We examine studies reporting miRNAs that directly target structural ECM molecules such as collagens, laminins, fibronectin, hyaluronan-related enzymes, and proteoglycans, as well as miRNAs that indirectly regulate ECM dynamics through modulation of matrix metalloproteinases, signaling pathways, and transcription factors. The collected evidence indicates that miRNAs form complex regulatory networks that influence tumor proliferation, invasion, metastasis, angiogenesis, immune evasion, and therapy resistance by reshaping the tumor microenvironment. Tumor-suppressive miRNAs generally inhibit ECM remodeling and metastatic behavior, whereas oncogenic miRNAs promote matrix degradation and a pro-invasive microenvironment. Importantly, many miRNAs exert pleiotropic effects by targeting multiple components of interconnected signaling pathways, resulting in context-dependent outcomes during melanoma progression. Overall, miRNA-dependent regulation of the ECM represents a crucial layer of control in melanoma biology. Understanding these regulatory circuits may provide novel opportunities for biomarker development and therapeutic intervention targeting both tumor cells and their surrounding microenvironment.