Abstract
MicroRNAs (miRNAs) are small non-coding RNAs, which play important roles in regulating various biological functions. Many available miRNA databases have provided a large number of valuable resources for miRNA investigation. However, not all existing databases provide comprehensive information regarding the transcriptional regulatory regions of miRNAs, especially typical enhancer, super-enhancer (SE), and chromatin accessibility regions. An increasing number of studies have shown that the transcriptional regulatory regions of miRNAs, as well as related single-nucleotide polymorphisms (SNPs) and transcription factors (TFs) have a strong influence on human diseases and biological processes. Here, we developed a comprehensive database for the human transcriptional regulation of miRNAs (TRmir), which is focused on providing a wealth of available resources regarding the transcriptional regulatory regions of miRNAs and annotating their potential roles in the regulation of miRNAs. TRmir contained a total of 5,754,414 typical enhancers/SEs and 1,733,966 chromatin accessibility regions associated with 1,684 human miRNAs. These regions were identified from over 900 human H3K27ac ChIP-seq, ATAC-seq, and DNase-seq samples. Furthermore, TRmir provided detailed (epi)genetic information about the transcriptional regulatory regions of miRNAs, including TFs, common SNPs, risk SNPs, linkage disequilibrium (LD) SNPs, expression quantitative trait loci (eQTLs), 3D chromatin interactions, and methylation sites, especially supporting the display of TF binding sites in the regulatory regions of over 7,000 TF ChIP-seq samples. In addition, TRmir integrated miRNA expression and related disease information, supporting extensive pathway analysis. TRmir is a powerful platform that offers comprehensive information about the transcriptional regulation of miRNAs for users and provides detailed annotations of regulatory regions. TRmir is free for academic users and can be accessed at http://bio.liclab.net/trmir/index.html.
Highlights
MicroRNAs are single-stranded small molecular RNAs, 21–23 bases in size produced by Dicer processing of single-stranded RNA hairpin loop precursors
We provided more detailed annotation information for the three regulatory regions mentioned before including common single-nucleotide polymorphisms (SNPs), risk SNPs, eQTLs, transcription factors (TFs), and methylation sites (450 K array, whole-genome shotgun bisulfite sequencing), histone modifications, and 3D chromatin interactions (Figure 2F)
As an example, when users input hsa-mir-23a, they can find that the relationship between miRNA and the promoter was validated by chromatin interaction data from the “Interaction” module
Summary
MicroRNAs (miRNAs) are single-stranded small molecular RNAs, 21–23 bases in size produced by Dicer processing of single-stranded RNA hairpin loop precursors. It is worth noting that miRNAs are often regulated by related super- or typical enhancers in addition to promoters (Duan et al, 2016; Suzuki et al, 2017; Sin-Chan et al, 2019; Ri et al, 2020) Typical enhancers, such as distal cis-regulatory DNA elements positively participate in the regulation of genes in a tissue-specific manner (Shlyueva et al, 2014). Some studies have shown that over 100 miRNAs were epigenetically regulated in different cancers, and the methylation frequency of human miRNA genes appeared to be much higher than that of proteincoding genes (Weber et al, 2007; Kunej et al, 2011) Consistent with these findings, researchers have found that miRNA genes frequently overlapped the cancer-associated genomic
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