Joint Genome-Wide Profiling of miRNA and mRNA Expression in Alzheimer's Disease Cortex Reveals Altered miRNA Regulation

Abstract

Although microRNAs are being extensively studied for their involvement in cancer and development, little is known about their roles in Alzheimer's disease (AD). In this study, we used microarrays for the first joint profiling and analysis of miRNAs and mRNAs expression in brain cortex from AD and age-matched control subjects. These data provided the unique opportunity to study the relationship between miRNA and mRNA expression in normal and AD brains. Using a non-parametric analysis, we showed that the levels of many miRNAs can be either positively or negatively correlated with those of their target mRNAs. Comparative analysis with independent cancer datasets showed that such miRNA-mRNA expression correlations are not static, but rather context-dependent. Subsequently, we identified a large set of miRNA-mRNA associations that are changed in AD versus control, highlighting AD-specific changes in the miRNA regulatory system. Our results demonstrate a robust relationship between the levels of miRNAs and those of their targets in the brain. This has implications in the study of the molecular pathology of AD, as well as miRNA biology in general.

Different micro-RNA expression profiles distinguish subtypes of neuroendocrine tumors of the lung: results of a profiling study

“…2,3,12,13 Therefore, miRNAs are involved in a wide range of biological functions, including cellular proliferation, differentiation, angiogenesis, apoptosis, and metastatic potential. 2,[12][13][14][15][16][17] Aberrant miRNA expression has been reported to be involved in the pathogenesis of Alzheimer's disease, 18 cardiovascular disease, 19 spinal motor neuron anomalies, 20 and numerous others. 2 Furthermore, deregulated expression of miRNAs has been identified in a variety of human malignancies, 12,13,[21][22][23][24][25][26][27][28][29] suggesting that miRNAs function as potential oncogenic factors or tumor suppressors, depending on the cell type or tissue investigated and their target genes.…”

Advances in MicroRNAs and Alzheimer’s Disease Research

“…Microarray techniques, based on correlation methods, are proving to be powerful tools for investigation on miRNAs deregulation in AD. The expression of 5-6% of miRNAs was affected by AD at statistical significant level in the studies described above (Hebert et al, 2008;Cogswell et al, 2008;Nunez-Iglesias et al, 2010) suggesting that a substantial number of miRNAs are deregulated in this pathology. …”

“…These data provided the unique opportunity to study the relationship between miRNA and mRNA expression in normal and AD brains. Starting from genome-wide miRNA and mRNA data expression, analysis was carried out to determine the correlation between levels of miRNAs and their target mRNAs (Nunez-Iglesias et al, 2010). The results reveal that most miRNA-mRNA pairs are actually uncorrelated making more difficult to understand the correlation level between miRNAs with their targets.…”

“…Among the processes most positively correlated with their regulating miRNA, the authors found some specific processes, including metabolism of both carbohydrates and fatty acid, as well as protein refolding which indicate the importance of these processes in the brain. Among the processes most negatively correlated are oxygen transport, cell adhesion, inflammatory response, cytoskeletal organization and dendrite development (Nunez-Iglesias et al, 2010). The method depicted can find active miRNA-mRNA relationships dependent from the tissue context.…”

Constructing and characterizing a bioactive small molecule and microRNA association network for Alzheimer's disease

“…We next used the R package of 'metaMA' to implement meta-analysis based on the theory of effect size combination, in which the 'SMVar' method was applied to calculate the gene differential expression levels for each case-control study (details in the electronic supplementary material, S3). For miRNAs, the differentially expressed miRNAs were selected based on the empirical Bayes procedure, which was performed in Nunez-Iglesias et al [36]. We then reserved the miRNAs, which were licensed by miRBase (v. 9.1) and provided targets in our integrated miRNAs target genes dataset.…”