Department of Internal Medicine, Division of Pulmonary Diseases and Critical Care Medicine, Virginia Commonwealth University, 1250 E. Marshall Street, Richmond, VA 23298, USA.
Genes (Basel). 2023 May 12;14(5):1075. doi: 10.3390/genes14051075.
miRNAs are some of the most well-characterized regulators of gene expression. Integral to several physiological processes, their aberrant expression often drives the pathogenesis of both benign and malignant diseases. Similarly, DNA methylation represents an epigenetic modification influencing transcription and playing a critical role in silencing numerous genes. The silencing of tumor suppressor genes through DNA methylation has been reported in many types of cancer and is associated with tumor development and progression. A growing body of literature has described the crosstalk between DNA methylation and miRNAs as an additional layer in the regulation of gene expression. Methylation in miRNA promoter regions inhibits its transcription, while miRNAs can target transcripts and subsequently regulate the proteins responsible for DNA methylation. Such relationships between miRNA and DNA methylation serve an important regulatory role in several tumor types and highlight a novel avenue for potential therapeutic targets. In this review, we discuss the crosstalk between DNA methylation and miRNA expression in the pathogenesis of cancer and describe how miRNAs influence DNA methylation and, conversely, how methylation impacts the expression of miRNAs. Finally, we address how these epigenetic modifications may be leveraged as biomarkers in cancer.
miRNAs 是基因表达最具特征性的调控因子之一。它们在多个生理过程中不可或缺，其异常表达通常会导致良性和恶性疾病的发病机制。同样，DNA 甲基化是一种影响转录的表观遗传修饰，在沉默许多基因方面发挥着关键作用。许多类型的癌症中都报道了肿瘤抑制基因通过 DNA 甲基化沉默，并且与肿瘤的发生和发展有关。越来越多的文献描述了 DNA 甲基化和 miRNA 之间的串扰，作为基因表达调控的另一个层面。miRNA 启动子区域的甲基化抑制其转录，而 miRNA 可以靶向转录本，进而调节负责 DNA 甲基化的蛋白质。miRNA 和 DNA 甲基化之间的这种关系在几种肿瘤类型中起着重要的调节作用，并为潜在的治疗靶点提供了新的途径。在这篇综述中，我们讨论了 DNA 甲基化和 miRNA 表达在癌症发病机制中的相互作用，并描述了 miRNA 如何影响 DNA 甲基化，以及反之亦然，甲基化如何影响 miRNA 的表达。最后，我们探讨了这些表观遗传修饰如何作为癌症的生物标志物加以利用。
