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Review
. 2023 May 12;14(5):1075.
doi: 10.3390/genes14051075.

Crosstalk between miRNAs and DNA Methylation in Cancer

Michela Saviana  1 , Patricia Le  1 , Lavender Micalo  1 , Daniel Del Valle-Morales  1 , Giulia Romano  1 , Mario Acunzo  1 , Howard Li  1 , Patrick Nana-Sinkam  1
Affiliations
Review

Crosstalk between miRNAs and DNA Methylation in Cancer

Michela Saviana et al. Genes (Basel). .

Abstract

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.

Keywords: DNA methylation; cancer; miRNA.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Schematic representation of the mechanism of DNA methylation and miRNA biogenesis. (A) Maintenance of methylation occurs during DNA replication. The histone H3 modification H3k9me3 recruits DMNT1 to methylate the daughter strand. (B) De novo methylation occurs at CpG locations throughout the genome. The histone H3 modification H3K36me3 inhibits the methylation activity of DNMT2/3. Unmethylated H3K36 recruits DNMT3A/B to the CpG sites, causing its hypermethylation. (C) miRNA biogenesis starts in the nucleus where the pri-miRNA is synthesized and then cropped by Drosha/DGCR8, converting into pre-miRNA. Exportin 5 mediates the pre-miRNA transport from the nucleus to the cytoplasm where it is processed by Dicer, producing a mature miRNA duplex of 22 nucleotides. Mature miRNA is loaded in the RISC complex that unwinds the duplex. The passenger strand is expulsed, while the guide strand is retained in the RISC complex that coordinates the interaction between the miRNA and its mRNA target. Created with BioRender, https://www.biorender.com/ (accessed on 8 May 2023).
Figure 2
Figure 2
Mechanism of mutual regulation between miRNA and DNA methylation. Created with BioRender, https://www.biorender.com/ (accessed on 8 May 2023).
Figure 3
Figure 3
Overview of the epigenetically regulated miRNA and miRNA that regulates DNA methylation in various human cancers. Created with BioRender, https://www.biorender.com/ (accessed on 8 May 2023).
See this image and copyright information in PMC

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