Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2017 Mar 4;12(3):187-197.
doi: 10.1080/15592294.2016.1273308. Epub 2017 Jan 6.

Mutual regulation of microRNAs and DNA methylation in human cancers

Sumei Wang  1   2 , Wanyin Wu  1 , Francois X Claret  2   3
Affiliations
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.

PubMed Disclaimer

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.
See this image and copyright information in PMC

References

    1. Richardson BC, Patel DR. Epigenetics in 2013. DNA methylation and miRNA: key roles in systemic autoimmunity. Nat Rev Rheumatol 2014; 10:72-4; 4332710; PMID:24418763; http://dx.doi.org/2607737310.1038/nrrheum.2013.211 - DOI - PMC - PubMed
    1. Hayes J, Peruzzi PP, Lawler S. MicroRNAs in cancer: biomarkers, functions and therapy. Trends Mol Med 2014; 20:460-9; PMID:25027972; http://dx.doi.org/2607737310.1016/j.molmed.2014.06.005 - DOI - PubMed
    1. Jonas S, Izaurralde E. Towards a molecular understanding of microRNA-mediated gene silencing. Nat Rev Genet 2015; 16:421-33; PMID:26077373 doi:10.1038/nrg3965 - DOI - PubMed
    1. Sharma S, Kelly TK, Jones PA. Epigenetics in cancer. Carcinogenesis 2010; 31:27-36; 2802667; PMID:19752007; http://dx.doi.org/10.1093/carcin/bgp220 - DOI - PMC - PubMed
    1. Sandoval J, Esteller M. Cancer epigenomics: beyond genomics. Curr Opin Genet Dev 2012; 22:50-5; PMID:22402447; http://dx.doi.org/1537207210.1016/j.gde.2012.02.008 - DOI - PubMed