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Aberrant DNA methylation of microRNA genes in human breast cancer – a critical appraisal

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Abstract

Aberrant DNA methylation of regulatory sequences is a well-documented mechanism of functional deletion of genes with anti-tumourigenic properties including microRNAs. This review discusses the publications describing aberrant methylation of microRNA genes in human breast cancer cells. Among the anti-tumourigenic properties of epigenetically inactivated microRNA genes, the inhibition of proliferation and of epithelial-to-mesenchymal transition (EMT) are the best studied. Several studies are conceptually very interesting and present a comprehensive functional characterization of anti-tumorigenic microRNAs. The link between microRNA expression and gene methylation is not addressed directly by all studies and a number of studies are limited in their strength by not including primary breast cancer specimens or by analysing very small sets of primary human specimens. The publications cover a wide range of DNA methylation detection techniques, often making direct comparison of results challenging. Despite the identification and thorough characterization of many interesting candidates and functionally important microRNA genes affected by DNA methylation, the translation of microRNA gene methylation as a new biomarker into the daily routine practice has not yet worked out.

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Fig. 1
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Abbreviations

EMT:

Epithelial-to-mesenchymal transition

HMEC:

Human mammary epithelial cells

HMF:

Human mammary fibroblasts

MSC:

Mesenchymal stem cells

MSP:

Methylation-specific PCR

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Acknowledgment

The author would like to thank, as always, Britta Hasemeier for indispensable help with Fig. 1.

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  1. Institute of Pathology, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, 30625, Hannover, Germany

    Ulrich Lehmann

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  1. Ulrich Lehmann
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Correspondence to Ulrich Lehmann.

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Lehmann, U. Aberrant DNA methylation of microRNA genes in human breast cancer – a critical appraisal. Cell Tissue Res 356, 657–664 (2014). https://doi.org/10.1007/s00441-014-1793-0

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