Finding microRNA regulatory modules in human genome using rule induction

Background: MicroRNAs (miRNAs) are a class of small non-coding RNA molecules (20-24 nt), which are believed to participate in repression of gene expression. They play important roles in several biological processes (e.g. cell death and cell growth). Both experimental and computational approaches have been used to determine the function of miRNAs in cellular processes. Most efforts have concentrated on identification of miRNAs and their target genes. However, understanding the regulatory mechanism of miRNAs in the gene regulatory network is also essential to the discovery of functions of miRNAs in complex cellular systems. To understand the regulatory mechanism of miRNAs in complex cellular systems, we need to identify the functional modules involved in complex interactions between miRNAs and their target genes. Results: We propose a rule-based learning method to identify groups of miRNAs and target genes that are believed to participate cooperatively in the post-transcriptional gene regulation, so-called miRNA regulatory modules (MRMs). Applying our method to human genes and miRNAs, we found 79 MRMs. The MRMs are produced from multiple information sources, including miRNA-target binding information, gene expression and miRNA expression profiles. Analysis of two first MRMs shows that these MRMs consist of highly-related miRNAs and their target genes with respect to biological processes. Conclusion: The MRMs found by our method have high correlation in expression patterns of miRNAs as well as mRNAs. The mRNAs included in the same module shared similar biological functions, indicating the ability of our method to detect functionality-related genes. Moreover, review of the literature reveals that miRNAs in a module are involved in several types of human cancer

Molecular medicine of microRNAs: structure, function and implications for diabetes

MicroRNAs (miRNAs) are a family of endogenous small noncoding RNA molecules, of 19–28 nucleotides in length. In humans, up to 3% of all genes are estimated to encode these evolutionarily conserved sequences. miRNAs are thought to control expression of thousands of target mRNAs. Mammalian miRNAs generally negatively regulate gene expression by repressing translation, possibly through effects on mRNA stability and compartmentalisation, and/or the translation process itself. An extensive range of in silico and experimental techniques have been applied to our understanding of the occurrence and functional relevance of such sequences, and antisense technologies have been successfully used to control miRNA expression in vitro and in vivo. Interestingly, miRNAs have been identified in both normal and pathological conditions, including differentiation and development, metabolism, proliferation, cell death, viral infection and cancer. Of specific relevance and excitement to the area of diabetes research, miRNA regulation has been implicated in insulin secretion from pancreatic β-cells, diabetic heart conditions and nephropathy. Further analyses of miRNAs in vitro and in vivo will, undoubtedly, enable us determine their potential to be exploited as therapeutic targets in diabetes