MicroRNA silencing by DNA methylation in human cancer: A literature analysis

Abstract

MicroRNAs (miRNAs) are small non-coding RNAs that post-transcriptionally regulate the expression of target mRNAs. MicroRNA genes themselves are regulated through epigenetic mechanisms, such as histone modifications and/or DNA methylation of CpG islands. Aberrant CpG island methylation patterns are frequently associated with cancer and thus researching DNA methylation of miRNA genes is a topic of increased research interest. Large quantities of available data from various studies are fragmented and incomplete; therefore, integration was performed. Data from 150 articles revealed 180 miRNA genes shown to be regulated via DNA methylation in 36 cancer types. From the total of 2588 known mature miRNA 6.9% (180/2588) miRNAs have been shown to be epigenetically regulated by DNA methylation. 45.5% (82/180) of miRNA genes were shown to be methylated in at least two cancer types among them hsa-miR-34b, hsa-miR-34c and hsa-miR-34a were found to be silenced in 24, 21 and 17 cancer types, respectively. The other 54.4% (98/180) miRNA genes regulated by DNA methylation were found to be specific for a certain type of cancer and therefore represent specific biomarker potential. Because specific miRNAs have diagnostic, prognostic and therapeutic potential, the systematically review of the field offers an overview of the field and facilitates experiment planning, generation of more targeted hypotheses and more efficient biomarker and target development.