The Non-Coding Landscape of Cutaneous Malignant Melanoma: A Possible Route to Efficient Targeted Therapy

SIMPLE SUMMARY: Despite improvements in cancer therapy, cutaneous malignant melanoma often remains unresponsive or quickly acquires drug resistance, proving fatal in advanced stages. Studies have shown that non-coding RNA molecules play a role in treatment-resistance. In this paper, we summarised the impact of miRNAs and lncRNAs on melanoma invasion and metastasis, pointing out their interference with BRAF inhibitors and immunotherapy. Important candidates include miR-28, miR-100, miR-125a, miR-125b, miR-200c, miR-211, SAMMSON, MELOE and HOTAIR. We also highlighted the potential of ncRNAs as promising biomarkers and molecular therapeutic targets for prospective clinical applications. ABSTRACT: Considered to be highly lethal if not diagnosed in early stages, cutaneous malignant melanoma is among the most aggressive and treatment-resistant human cancers, and its incidence continues to rise, largely due to ultraviolet radiation exposure, which is the main carcinogenic factor. Over the years, researchers have started to unveil the molecular mechanisms by which malignant melanoma can be triggered and sustained, in order to establish specific, reliable biomarkers that could aid the prognosis and diagnosis of this fatal disease, and serve as targets for development of novel efficient therapies. The high mutational burden and heterogeneous nature of melanoma shifted the main focus from the genetic landscape to epigenetic and epitranscriptomic modifications, aiming at elucidating the role of non-coding RNA molecules in the fine tuning of melanoma progression. Here we review the contribution of microRNAs and lncRNAs to melanoma invasion, metastasis and acquired drug resistance, highlighting their potential for clinical applications as biomarkers and therapeutic targets.