Orlandella Francesca Maria, Arcone Rosaria, Luciano Neila, Salvatore Giuliana, Motti Maria Letizia
Department of Medical, Human Movement and Well-Being Sciences, University of Naples Parthenope, 80133 Naples, Italy.
CEINGE-Biotecnologie Avanzate "Franco Salvatore", 80131 Naples, Italy.
Cancers (Basel). 2025 Apr 9;17(8):1273. doi: 10.3390/cancers17081273.
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（lncRNAs）的正确表达可能对黑色素瘤患者的治疗具有重要意义。在此背景下，我们旨在剖析黑色素瘤中lncRNAs的主要特征及其与该疾病进展相关信号通路的相互作用。我们还强调了基于核酸的技术和天然化合物（即植物化学物质）作为一种治疗工具，在癌细胞中增加或沉默其表达的作用。最后，我们探讨了纳米技术作为递送系统的进展，以有效地将这些化学物质输送到癌细胞中，从而限制其潜在的脱靶效应。文献分析表明，HOTAIR、MALAT1和H19是黑色素瘤中研究最多的致癌lncRNAs，而MEG3是该癌症中表达降低的重要肿瘤抑制因子。这些lncRNAs的异常表达影响癌症的几个特征，如增殖、迁移和上皮-间质转化，促进黑色素瘤的可塑性和耐药性。在此框架下，小干扰RNA（siRNA）、反义寡核苷酸和CRISPR-Cas9基因组编辑似乎是恢复lncRNA生理表达最有效的核酸策略，而姜黄素、白藜芦醇和槲皮素是能够靶向并影响癌症中改变的lncRNAs表达的主要植物化学物质。总体而言，本研究全面概述了lncRNAs在黑色素瘤细胞表型可塑性中的作用以及使用基于RNA的疗法和天然产物对其进行潜在靶向的情况。
