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Archives of Toxicology

, Volume 90, Issue 10, pp 2405–2419 | Cite as

MicroRNA epigenetic signatures in human disease

  • Klara Piletič
  • Tanja Kunej
Review Article

Abstract

MicroRNAs (miRNAs) are short non-coding RNAs that act as important regulators of gene expression as part of the epigenetic machinery. In addition to posttranscriptional gene silencing by miRNAs, the epigenetic mechanisms also include DNA methylation, histone modifications and their crosstalk. Epigenetic modifications were reported to play an important role in many disease onsets and progressions and can be used to explain several features of complex diseases, such as late onset and fluctuation of symptoms. However, miRNAs not only function as a part of epigenetic machinery, but are also epigenetically modified by DNA methylation and histone modification like any other protein-coding gene. There is a strong connection between epigenome and miRNome, and any dysregulation of this complex system can result in various physiological and pathological conditions. In addition, miRNAs play an important role in toxicogenomics and may explain the relationship between toxicant exposure and tumorigenesis. The present review provides information on 63 miRNA genes shown to be epigenetically regulated in association with 21 diseases, including 11 cancer types: cardiac fibrosis, cardiovascular disease, preeclampsia, Hirschsprung’s disease, rheumatoid arthritis, systemic sclerosis, systemic lupus erythematosus, temporal lobe epilepsy, autism, pulmonary fibrosis, melanoma, acute myeloid leukemia, chronic lymphocytic leukemia, colorectal, gastric, cervical, ovarian, prostate, lung, breast, and bladder cancer. The review revealed that hsa-miR-34a, hsa-miR-34b, and hsa-miR-34c are the most frequently reported epigenetically dysregulated miRNAs. There is a need to further study molecular mechanisms of various diseases to better understand the crosstalk between epigenetics and gene expression and to develop new therapeutic options and biomarkers.

Keywords

Cancer DNA methylation Epigenetics Histone modification MicroRNA (miRNA) Toxicology 

Notes

Acknowledgments

We thank Tasha Murgel for critical reading of our manuscript.

Funding

This study was funded by the Slovenian Research Agency (ARRS) through the Research Program Comparative genomics and genome biodiversity (Grant Number P4-0220).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

204_2016_1815_MOESM1_ESM.pptx (352 kb)
Supplementary material 1 (PPTX 352 kb)
204_2016_1815_MOESM2_ESM.pdf (257 kb)
Supplementary material 2 (PDF 257 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  1. 1.Department of Animal Science, Biotechnical FacultyUniversity of LjubljanaDomzaleSlovenia

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