Abstract
Noncoding, endogenous microRNAs (miRNAs) are fairly well known for regulating gene expression rather than protein coding. Dysregulation of miRNA gene, either upregulated or downregulated, may lead to severe diseases or oncogenesis, especially when the miRNA disorder involves significant bioreactions or pathways. Thus, how miRNA genes are transcriptionally regulated has been highlighted as well as target recognition in recent years. In this study, a large-scale investigation of novel cis- and trans-elements was undertaken to further determine TF-miRNA regulatory relations, which are necessary to unravel the transcriptional regulation of miRNA genes. Based on miRNA and annotated gene expression profiles, the term “coTFBS” was introduced to detect common transcription factors and the corresponding binding sites within the promoter regions of each miRNA and its coexpressed annotated genes. The computational pipeline was successfully established to filter redundancy due to short sequence motifs for TFBS pattern search. Eventually, we identified more convinced TF-miRNA regulatory relations for 225 human miRNAs. This valuable information is helpful in understanding miRNA functions and provides knowledge to evaluate the therapeutic potential in clinical research. Once most expression profiles of miRNAs in the latest database are completed, TF candidates of more miRNAs can be explored by this filtering approach in the future.
Highlights
Among functional noncoding ribonucleic acids (RNAs), microRNAs are tiny molecules (∼21–23 nt) with giant roles. miRNAs participate in gene regulation by targeting messenger RNAs and influencing their stability and the initiation of translation
Our result shows that P300 is the transcription factors (TFs) candidate of miR-224, and its transcription factor binding sites (TFBSs) can be found in 227 coexpressed gene promoters
Not all of ribonucleic acids (RNAs) are translated to proteins. miRNAs are such noncoding RNAs which play critical roles in gene regulation, even if it is generally believed that proteins convey vital information from genes and execute biological functions to maintain life processes
Summary
Among functional noncoding RNAs (ncRNAs), microRNAs (miRNAs) are tiny molecules (∼21–23 nt) with giant roles. miRNAs participate in gene regulation by targeting messenger RNAs (mRNAs) and influencing their stability and the initiation of translation. Among functional noncoding RNAs (ncRNAs), microRNAs (miRNAs) are tiny molecules (∼21–23 nt) with giant roles. MiRNAs participate in gene regulation by targeting messenger RNAs (mRNAs) and influencing their stability and the initiation of translation. In recent years, elucidating transcriptional regulatory mechanisms of miRNA genes has been highlighted when studying miRNA function. Core promoters of miRNA genes were promptly identified for depicting full-length primary transcripts [3,4,5]. Highthroughput sequencing datasets derived from epigenetic signature and TSS-relevant experiments unfold transcriptional start sites (TSSs) of miRNAs and offer a practical strategy to determine miRNA promoters [6,7,8,9]. To further understand upstream regulatory elements controlling miRNA expression, transcription factors (TFs)
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