Oxidative-Stress-Sensitive microRNAs in UV-Promoted Development of Melanoma

SIMPLE SUMMARY: Exposure to ultraviolet (UV) rays from the sun is one of the most important modifiable risk factors for skin cancer. Melanoma is the most life-threatening type of skin cancer. UV-induced DNA damage and oxidative stress represent two main mechanisms that, directly and indirectly, contribute to melanomagenesis. In addition, an interplay of abnormally expressed microRNAs (miRNAs) and redox imbalance is a hallmark in several cancers, including melanoma. UV radiation can be the central hub between these two cellular aberrations, as it is able to stimulate both. Here, to gain new mechanistic insights into melanomagenesis and identify new therapeutic targets for the prevention and treatment of melanoma, we report current evidence suggesting a complex interaction between UV-promoted deregulation of redox-sensitive miRNAs and known signal-transduction pathways underlying malignant transformation of melanocytes to melanoma. ABSTRACT: Melanoma is the most aggressive and life-threatening form of skin cancer. Key molecular events underlying the melanocytic transformation into malignant melanoma mainly involve gene mutations in which exposure to ultraviolet (UV) radiation plays a prominent role. However, several aspects of UV-induced melanomagenesis remain to be explored. Interestingly, redox-mediated signaling and perturbed microRNA (miRNA) profiles appear to be interconnected contributing factors able to act synergistically in melanoma initiation and progression. Since UV radiation can promote both redox imbalance and miRNA dysregulation, a harmful crosstalk between these two key cellular networks, with UV as central hub among them, is likely to occur in skin tissue. Therefore, decoding the complex circuits that orchestrate the interaction of UV exposure, oxidative stress, and dysregulated miRNA profiling can provide a deep understanding of the molecular basis of the melanomagenesis process. Furthermore, these mechanistic insights into the reciprocal regulation between these systems could have relevant implications for future therapeutic approaches aimed at counteracting UV-induced redox and miRNome imbalances for the prevention and treatment of malignant melanoma. In this review, we illustrate current information on the intricate connection between UV-induced dysregulation of redox-sensitive miRNAs and well-known signaling pathways involved in the malignant transformation of normal melanocytes to malignant melanoma.