Increasing evidence revealed that restoring the correct expression of lncRNAs could have implications in the management of melanoma patients. In this context, here, we aim to dissect the main characteristics of lncRNAs altered in melanoma and their crosstalk with the signaling pathways involved in the progression of this disease. We also highlight the role of nucleic acid-based techniques and natural compounds (i.e., phytochemicals) as a therapeutic tool to increase or silence their expression in cancer cells. Finally, we explore the advances in nanotechnologies as delivery systems to efficiently carry these chemicals into cancer cells, thus limiting their potential off-target effects. The analysis of the literature showed that HOTAIR, MALAT1, and H19 are the oncogenic lncRNAs most studied in melanoma, while MEG3 is an important tumor suppressor decreased in this cancer. The aberrant expression of these lncRNAs affects several hallmarks of cancer, e.g., proliferation, motility, and epithelial to mesenchymal transition, promoting the melanoma plasticity and drug resistance. In this frame, siRNA, antisense oligonucleotide, and CRISPR-Cas9 genome editing appear to be the most effective nucleic acid strategies to restore the physiologic expression of lncRNA, while curcumin, resveratrol, and quercetin are the main phytochemicals able to target and influence the expression of lncRNAs altered in cancer. Overall, this study provides a comprehensive overview regarding the role of lncRNAs in the phenotype plasticity of melanoma cells and their potential targeting using RNA-based therapy and natural products.
越来越多的证据表明，恢复长链非编码RNA（lncRNA）的正确表达对黑色素瘤患者的治疗具有重要意义。在此背景下，本研究旨在解析黑色素瘤中异常lncRNA的主要特征及其与疾病进展相关信号通路的交互作用。同时，我们重点探讨了基于核酸的技术和天然化合物（如植物化学物质）作为治疗工具，在癌细胞中上调或沉默这些lncRNA表达的作用。最后，我们评估了纳米技术作为递送系统的最新进展，这些技术能有效将化学物质输送至癌细胞，从而降低其潜在的脱靶效应。文献分析显示，HOTAIR、MALAT1和H19是黑色素瘤中研究最广泛的致癌lncRNA，而MEG3则是在该癌症中表达降低的重要抑癌lncRNA。这些lncRNA的异常表达影响癌症的多个特征，如增殖、运动性和上皮间质转化，从而促进黑色素瘤的可塑性和耐药性。在此框架下，siRNA、反义寡核苷酸和CRISPR-Cas9基因组编辑技术似乎是最有效的核酸策略，可恢复lncRNA的生理表达；而姜黄素、白藜芦醇和槲皮素则是能够靶向并影响癌症中异常lncRNA表达的主要植物化学物质。总体而言，本研究全面概述了lncRNA在黑色素瘤细胞表型可塑性中的作用，以及基于RNA的疗法和天然产物靶向这些lncRNA的潜力。
Novel Biological Strategies for Melanoma Therapy: A Focus on lncRNAs and Their Targeting
肿瘤(癌症)患者之家