Data integration of 104 studies related with microRNA epigenetics revealed that miR-34 gene family is silenced by DNA methylation in the highest number of cancer types

There is an increasing research interest regarding deregulation of microRNA (miRNA) expression by DNA methylation in cancer. The aim of this study was to integrate data from publications and identify miRNA genes shown to be silenced in the highest number of cancer types and thus facilitate biomarker and therapeutic development. We integrated relevant data from 104 published scientific articles. The following databases and bioinformatics tools were used for the analysis: miRBase, miRNA Genomic Viewer, MultAlin, miRNA SNiPer, TargetScan, Ensembl, MethPrimer, TarBase, miRecords, and ChIPBase. Among 2578 currently known human miRNAs and 158 known to be regulated by DNA methylation, miR-34 gene family (miR-34a, -34b, and -34c) was shown to be silenced by DNA methylation in the highest number of cancer types. Consequently, we developed the miR-34 gene family regulatory atlas, consisting of its upstream regulators and downstream targets including transcription factor binding sites (TFBSs), CpG islands, genetic variability and overlapping QTL. MicroRNA-34 gene family has a potential as a cancer biomarker and target for epigenetic drugs. This potential has already been recognized as MRX34 is well into phase I studies. The developed miR-34 gene family regulatory atlas presented in this study provides a starting point for further analyses and could thus facilitate development of therapeutics.