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Review
, 12 (3), 187-197

Mutual Regulation of microRNAs and DNA Methylation in Human Cancers

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Review

Mutual Regulation of microRNAs and DNA Methylation in Human Cancers

Sumei Wang et al. Epigenetics.

Abstract

microRNAs (miRNAs) and DNA methylation are the 2 epigenetic modifications that have emerged in recent years as the most critical players in the regulation of gene expression. Compelling evidence has indicated the roles of miRNAs and DNA methylation in modulating cellular transformation and tumorigenesis. miRNAs act as negative regulators of gene expression and are involved in the regulation of both physiologic conditions and during diseases, such as cancer, inflammatory diseases, and psychiatric disorders, among others. Meanwhile, aberrant DNA methylation manifests in both global genome changes and in localized gene promoter changes, which influences the transcription of cancer genes. In this review, we described the mutual regulation of miRNAs and DNA methylation in human cancers. miRNAs regulate DNA methylation by targeting DNA methyltransferases or methylation-related proteins. On the other hand, both hyper- and hypo-methylation of miRNAs occur frequently in human cancers and represent a new level of complexity in gene regulation. Therefore, understanding the mechanisms underlying the mutual regulation of miRNAs and DNA methylation may provide helpful insights in the development of efficient therapeutic approaches.

Keywords: Cancer; DNA methylation; epigenetics; microRNA; regulation; therapeutics.

Figures

Figure 1.
Figure 1.
Aberrant DNA methylation contributes to tumorigenesis (A). Hypermethylation of the promoter of tumor suppressor genes (TSGs) or gene family leads to its silencing and contributes to tumorigenesis. (B) Hypomethylation of oncogene promoters leads to their activation and contributes to tumorigenesis. (C) Genome-wide DNA hypomethylation may lead to chromosomal instability or cell differentiation, which contributes to tumorigenesis or inhibits tumorigenesis, respectively.
Figure 2.
Figure 2.
Feedback loops between miRNAs and DNA methylation in human cancers. (A) miRNAs regulate DNA methylation by targeting DNMTs or methylation-related critical proteins. (B) TS-miRNAs are hypermethylated (inhibiting TS-miRNAs expression) and onco-miRNAs are hypomethylated (promoting of onco-miRNAs expression) in human cancers.

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