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A dictionary on microRNAs and their putative target pathways.

ABSTRACT: While in the last decade mRNA expression profiling was among the most popular research areas, over the past years the study of non-coding RNAs, especially microRNAs (miRNAs), has gained increasing interest. For almost 900 known human miRNAs hundreds of pretended targets are known. However, there is only limited knowledge about putative systemic effects of changes in the expression of miRNAs and their regulatory influence. We determined for each known miRNA the biochemical pathways in the KEGG and TRANSPATH database and the Gene Ontology categories that are enriched with respect to its target genes. We refer to these pathways and categories as target pathways of the corresponding miRNA. Investigating target pathways of miRNAs we found a strong relation to disease-related regulatory pathways, including mitogen-activated protein kinase (MAPK) signaling cascade, Transforming growth factor (TGF)-beta signaling pathway or the p53 network. Performing a sophisticated analysis of differentially expressed genes of 13 cancer data sets extracted from gene expression omnibus (GEO) showed that targets of specific miRNAs were significantly deregulated in these sets. The respective miRNA target analysis is also a novel part of our gene set analysis pipeline GeneTrail. Our study represents a comprehensive theoretical analysis of the relationship between miRNAs and their predicted target pathways. Our target pathways analysis provides a 'miRNA-target pathway' dictionary, which enables researchers to identify target pathways of differentially regulated miRNAs.

SUBMITTER: Backes C

PROVIDER: S-EPMC2910047 | biostudies-literature | 2010 Jul

REPOSITORIES: biostudies-literature

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A dictionary on microRNAs and their putative target pathways.

Backes Christina C Meese Eckart E Lenhof Hans-Peter HP Keller Andreas A

Nucleic acids research 20100318 13

While in the last decade mRNA expression profiling was among the most popular research areas, over the past years the study of non-coding RNAs, especially microRNAs (miRNAs), has gained increasing interest. For almost 900 known human miRNAs hundreds of pretended targets are known. However, there is only limited knowledge about putative systemic effects of changes in the expression of miRNAs and their regulatory influence. We determined for each known miRNA the biochemical pathways in the KEGG an ...[more]

PMID: 20299343

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Project description:MicroRNAs (miRNAs/miRs) are small non‑coding RNAs (ncRNAs) that regulate gene expression. Emerging knowledge has suggested that miRNAs have a role in the pathogenesis of metabolic disorders, supporting the hypothesis that miRNAs may represent potential biomarkers or targets for this set of diseases. However, the current evidence is often controversial. Therefore, the aim of the present study was to determine the associations between miRNAs‑target genes, miRNA‑long ncRNAs (lncRNAs), and miRNAs‑small molecules in human metabolic diseases, including obesity, type 2 diabetes and non‑alcoholic fatty liver disease. The metabolic disease‑related miRNAs were obtained from the Human MicroRNA Disease Database (HMDD) and miR2Disease database. A search on the databases Matrix Decomposition and Heterogeneous Graph Inference (MDHGI) and DisGeNET were also performed. miRNAs target genes were obtained from three independent sources: Microcosm, TargetScan and miRTarBase. The interactions between miRNAs‑lncRNA and miRNA‑small molecules were performed using the miRNet web tool. The network analyses were performed using Cytoscape software. As a result, a total of 20 miRNAs were revealed to be associated with metabolic disorders in the present study. Notably, 6 miRNAs (miR‑17‑5p, miR‑29c‑3p, miR‑34a‑5p, miR‑103a‑3p, miR‑107 and miR‑132‑3p) were found in the four resources (HMDD, miR2Disease, MDHGI, and DisGeNET) used for these analyses, presenting a stronger association with the diseases. Furthermore, the target genes of these miRNAs participate in several pathways previously associated with metabolic diseases. In addition, interactions between miRNA‑lncRNA and miRNA‑small molecules were also found, suggesting that some molecules can modulate gene expression via such an indirect way. Thus, the results of this data mining and integration analysis provide further information on the possible molecular basis of the metabolic disease pathogenesis as well as provide a path to search for potential biomarkers and therapeutic targets concerning metabolic diseases.

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A dictionary on microRNAs and their putative target pathways.

Publications

A dictionary on microRNAs and their putative target pathways.

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