Article

Inferring functional miRNA-mRNA regulatory modules in epithelial-mesenchymal transition with a probabilistic topic model.

Kunming University of Science and Technology, Kunming, China.
Computers in biology and medicine (Impact Factor: 1.27). 01/2012; 42(4):428-37. DOI: 10.1016/j.compbiomed.2011.12.011
Source: PubMed

ABSTRACT MicroRNAs (miRNAs) play important roles in gene regulatory networks. In this paper, we propose a probabilistic topic model to infer regulatory networks of miRNAs and their target mRNAs for specific biological conditions at the post-transcriptional level, so-called functional miRNA-mRNA regulatory modules (FMRMs). The probabilistic model used in this paper can effectively capture the relationship between miRNAs and mRNAs in specific cellular conditions. Furthermore, the proposed method identifies negatively and positively correlated miRNA-mRNA pairs which are associated with epithelial, mesenchymal, and other condition in EMT (epithelial-mesenchymal transition) data set, respectively. Results on EMT data sets show that the inferred FMRMs can potentially construct the biological chain of 'miRNA→mRNA→condition' at the post-transcriptional level.

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    ABSTRACT: MicroRNAs (miRNAs), a class of endogenous small noncoding RNAs, mediate posttranscriptional regulation of protein-coding genes by binding chiefly to the 3' untranslated region of target mRNAs, leading to translational inhibition, mRNA destabilization or degradation. A single miRNA concurrently downregulates hundreds of target mRNAs designated "targetome", and thereby fine-tunes gene expression involved in diverse cellular functions, such as development, differentiation, proliferation, apoptosis and metabolism. Recently, we characterized the molecular network of the whole human miRNA targetome by using bioinformatics tools for analyzing molecular interactions on the comprehensive knowledgebase. We found that the miRNA targetome regulated by an individual miRNA generally constitutes the biological network of functionally-associated molecules in human cells, closely linked to pathological events involved in cancers and neurodegenerative diseases. We also identified a collaborative regulation of gene expression by transcription factors and miRNAs in cancer-associated miRNA targetome networks. This review focuses on the workflow of molecular network analysis of miRNA targetome in silico. We applied the workflow to two representative datasets, composed of miRNA expression profiling of adult T cell leukemia (ATL) and Alzheimer's disease (AD), retrieved from Gene Expression Omnibus (GEO) repository. The results supported the view that miRNAs act as a central regulator of both oncogenesis and neurodegeneration.
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