Angiogenesis, the formation of new blood vessels from pre-existing ones, is a crucial process in the progression and metastasis of melanoma. Recent research has highlighted the significant role of epigenetic modifications in regulating angiogenesis. This review comprehensively examines the current understanding of how epigenetic mechanisms, including DNA methylation, histone modifications, and non-coding RNAs, influence angiogenic pathways in melanoma. DNA methylation, a key epigenetic modification, can silence angiogenesis inhibitors such as thrombospondin-1 and TIMP3 while promoting pro-angiogenic factors like vascular endothelial growth factor (VEGF). Histone modifications, including methylation and acetylation, also play a pivotal role in regulating the expression of angiogenesis-related genes. For instance, the acetylation of histones H3 and H4 is associated with the upregulation of pro-angiogenic genes, whereas histone methylation patterns can either enhance or repress angiogenic signals, depending on the specific histone mark and context. Non-coding RNAs, particularly microRNAs (miRNAs) further modulate angiogenesis. miRNAs, such as miR-210, have been identified as key regulators, with miR-9 promoting angiogenesis by targeting E-cadherin and enhancing the expression of VEGF. This review also discusses the therapeutic potential of targeting epigenetic modifications to inhibit angiogenesis in melanoma. Epigenetic drugs, such as DNA methyltransferase inhibitors (e.g., 5-azacytidine) and histone deacetylase inhibitors (e.g., Vorinostat), have shown promise in preclinical models by reactivating angiogenesis inhibitors and downregulating pro-angiogenic factors. Moreover, the modulation of miRNAs and lncRNAs presents a novel approach for anti-angiogenic therapy.
血管生成，即从已有血管形成新血管的过程，在黑色素瘤的进展和转移中至关重要。近期研究强调了表观遗传修饰在调控血管生成中的重要作用。本综述全面探讨了目前对表观遗传机制如何影响黑色素瘤血管生成途径的理解，包括DNA甲基化、组蛋白修饰和非编码RNA。DNA甲基化作为一种关键的表观遗传修饰，能够沉默血管生成抑制剂如血小板反应蛋白-1和TIMP3，同时促进血管内皮生长因子（VEGF）等促血管生成因子。组蛋白修饰，包括甲基化和乙酰化，也在调控血管生成相关基因表达中发挥关键作用。例如，组蛋白H3和H4的乙酰化与促血管生成基因的上调相关，而组蛋白甲基化模式则可能增强或抑制血管生成信号，具体取决于特定的组蛋白标记和背景。非编码RNA，特别是微小RNA（miRNA），进一步调节血管生成。miRNA，如miR-210，已被确定为关键调节因子，其中miR-9通过靶向E-钙黏蛋白并增强VEGF表达来促进血管生成。本综述还讨论了靶向表观遗传修饰以抑制黑色素瘤血管生成的治疗潜力。表观遗传药物，如DNA甲基转移酶抑制剂（例如5-氮杂胞苷）和组蛋白去乙酰化酶抑制剂（例如伏立诺他），在临床前模型中显示出通过重新激活血管生成抑制剂和下调促血管生成因子而具有前景。此外，调节miRNA和长链非编码RNA为抗血管生成治疗提供了一种新方法。
Epigenetics and Control of Tumor Angiogenesis in Melanoma: An Update with Therapeutic Implications
肿瘤(癌症)患者之家