Introduction: Skin cancer of a malignant nature called Melanoma develops from melanocytes while appearing rapidly and showing high risk for metastasis along with resistance to current therapeutic approaches (1–5). The development of melanoma follows genetic mutation patterns together with epigenetic makeup changes and environmental exposure to UV radiation (2,5–7).
Small RNA molecules known as microRNAs (miRNAs) use sequence matching to bind their target mRNAs and regulate gene expression after transcription (1,8,9). The altered expression of miRNAs becomes a significant indicator of malignant melanoma development because these regulatory RNA molecules can profoundly affect tumor progression and metastasis as well as therapeutic resistance (3,10–20). Tumor-suppressive miR-21, miR-146a, and miR-214 show distinct changes during melanoma pathogenesis (6,14,21). Research has confirmed that miRNAs detected in bodily fluids function as accurate non-invasive biomarkers (12,13). The therapeutic applications and diagnostic value of melanoma cell communication in tumor micro environments can be found in their ability to use miRNAs (5,14,22,23). The field of melanoma research continues to examine miRNAs' fundamental biological functions in addition to their potential use in clinical applications (7,15–17).
Methods: A comprehensive search was conducted using Google Scholar, PubMed, and ScienceDirect to identify studies on miRNAs and melanoma published since 2020. The final selection included 52 studies categorized into pathogenesis, diagnostics, therapeutics, mechanistic pathways, and clinical applications. These studies were synthesized to provide a comprehensive overview of recent findings in the field.
Results: Two miRNA sequences, namely miR-143 and miR-127, display anti-tumor properties that prevent melanoma cells from moving to different body parts and force them to die (13,24). Melanoma cells move faster because of oncomiR miR-21, which makes cells move faster and invade more deeply and starts apoptosis through exosome-mediated transport (12,21).
MiR-183, miR-146a, and miR-214 help melanoma cells progress by promoting cell growth, migration, and epithelial-mesenchymal transition (EMT) (6,12). Additionally, miR-488-5p, miR-200b-3p, miR-200c, and miR-378a-5p influence metastasis and cell signaling regulation (12).
The progress of melanoma relies heavily on the activity of miR-130b-3p, as researchers have identified it as crucial for tumor development (5). Under hypoxic tumor microenvironment conditions, miRNA expression patterns alter, leading to altered protein levels of ALDOA, PKM2, and PRMT5, elevated production of miR-210 and miR-1290, and decreased activities of miR-23a-5p and miR-23b-5p (14,25).
Regulatory T cells (Tregs) increase in numbers because of TME conditions leading to tumor expansion and immune system evasion, according to research (15). Therapeutic research has made progress when targeting miRNAs as an intervention strategy. The preclinical effectiveness of tumor growth reduction has been demonstrated by LNA-anti-miR-21 inhibitors and miR-34a mimics (21). Extracellular vesicles and lipid nanoparticles helped stabilize miRNA delivery systems and achieved better therapeutic results, according to published research (21,23).
Therapies and new biomarkers become optimized through the application of CRISPR-based miRNA editing alongside multi-omics profiling approaches (21). Researchers have found that using anti-miR-146a along with anti-PD-1 therapy can reduce the size of tumors. When miRNA mimics are used, they can also boost immune responses and start the apoptosis process (7,12).
In clinical diagnostics, miRNAs like let-7a, miR-149, miR-211, and miR-191 are stable and can be used to diagnose melanoma and track its progression through biomarker analysis (16,17). The development of MELmiR-7 as a seven-miRNA combination serves to determine melanoma progression (17). Three exosomal biomarkers known as miR-125b, miR-106b, and miR-200c provide diagnostic strength according to research results (16).
The decreased levels of miR-1180-3p in melanoma patient plasma make it a suitable biomarker candidate (16). The analysis of blood-based miRNAs generates 0.78 sensitivity and 0.80 specificity rates for melanoma diagnosis according to research (26). Cytophone machines provide patients with important prognostic information about survival by detecting circulating tumor cells (CTCs) according to research.
Conclusion: The development of melanoma relies heavily upon miRNA regulation, which directly controls both tumor metastasis and therapy response as well as tumor progression. Among the relevant biomarkers are the crucial indicators miR-21 and miR-146a-5p. Tumor growth regulation and treatment sensitivity improvements emerge as promising applications of biomarker-based diagnosis. With more progress in miRNA profiling, delivery systems, and multi-omics integration methods, personalized melanoma treatments can be made that should give patients better outcomes. The field of melanoma treatment and targeted therapy shows promising signs of advancement due to these recent developments.