Pecorelli Alessandra, Valacchi Giuseppe
Department of Animal Science, N.C. Research Campus, Plants for Human Health Institute, North Carolina State University, Kannapolis, NC 28081, USA.
Department of Environment and Prevention, University of Ferrara, 44121 Ferrara, Italy.
Cancers (Basel). 2022 Jun 30;14(13):3224. doi: 10.3390/cancers14133224.
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.
黑色素瘤是皮肤癌中最具侵袭性且危及生命的类型。黑素细胞转变为恶性黑色素瘤背后的关键分子事件主要涉及基因突变，其中紫外线（UV）辐射起着重要作用。然而，紫外线诱导黑色素瘤发生的几个方面仍有待探索。有趣的是，氧化还原介导的信号传导和微RNA（miRNA）谱的紊乱似乎是相互关联的促成因素，能够在黑色素瘤的起始和进展中协同作用。由于紫外线辐射可促进氧化还原失衡和miRNA失调，这两个关键细胞网络之间可能会发生有害的相互作用，其中紫外线是它们之间的中心枢纽，这种相互作用可能发生在皮肤组织中。因此，解读协调紫外线暴露、氧化应激和失调的miRNA谱相互作用的复杂回路，可以深入了解黑色素瘤发生过程的分子基础。此外，对这些系统之间相互调节的机制性认识可能对未来旨在对抗紫外线诱导的氧化还原和miRNA组失衡以预防和治疗恶性黑色素瘤的治疗方法具有重要意义。在这篇综述中，我们阐述了关于紫外线诱导的氧化还原敏感型miRNA失调与正常黑素细胞向恶性黑色素瘤恶性转化所涉及的知名信号通路之间复杂联系的当前信息。
