Systematic analysis of regulation and functions of co-expressed microRNAs in humans

MicroRNAs (miRNAs) are a class of small non-coding RNA genes that post-transcriptionally regulate gene expression. With the development of high-throughput miRNA detection technology, researchers have begun to investigate the relationships between miRNA expression and its functions. In this study, we systematically analyzed the underlying molecular mechanisms and biological functions of co-expressed miRNAs. By integrating miRNA expression profiles, miRNA genome locations, transcriptional factors (TFs) of miRNAs and their target genes, we concluded that co-expressed miRNAs are more likely to be located in the same miRNA cluster (p = 6.05 x 10(-30)), are regulated by more common TFs (p = 9.17 x 10(-17)) and have consistent functions (p = 1.01 x 10(-6)). Moreover, among the top 10% (84) co-expressed miRNA pairs that are located on the same chromosomes, 37 miRNA pairs are located in the same cluster. Of the remaining 47 pairs, 36 miRNA pairs share more common TFs (>7). They account for 73/84 (86.9%) of total miRNA pairs. Finally, we further analyzed the top 10 co-expressed miRNA pairs. Almost all of these miRNA pairs are located in the same cluster, are regulated by many common TFs and have highly consistent functions, in agreement with previous reports. Thus, our study may provide an important reference for miRNA regulations and functions.