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Publication Abstract Display
Type: Published Abstract
Title: Alteration of gene regulatory networks through miRNA expression in the HIVinfected brain.
Authors: Tatro E, Nguyen T, Scott E, Masliah E, Achim C, Everall I
Year: 2009
Publication: Society for Neuroscience, Chicago, Illinois, October 17-21
Volume: Issue: Pages:
Abstract:Micro-RNAs (miRNAs) are small, non-coding RNAs that regulate gene networks, helping to control cell function and phenotype. The importance of miRNAs in the CNS is increasingly recognized. Past genomic studies have focused on coding messenger-RNA (mRNA) expression using large-scale hybridization-based array technology for elucidating gene expression in the brain during HIV-infection. Because miRNAs affect the downstream functions of mRNAs, it is desirable to understand both mRNA and miRNA changes that occur. HIV infection affects the CNS through inflammation and glial cell activation; leading to downstream long-term changes to cellular function in neurons and glia. One mechanism by which this may occur is through changes in miRNA repertoire. The present study was performed by pooling RNA isolated from the frontal cortex of 3 patients each into four groups: Control, HIV+, HIV/Major Depressive Disorder (HIV/MDD), and postmortem-confirmed HIV encephalitis (HIVE). The goals were to determine whether: 1. Changes in miRNA expression occurred in HIV, 2. Detectable miRNA expression of the FC could differentiate HIV from HIVE (overt pathological encephalitis) and HIV/MDD (neurobehavioral diagnostic category). We present a method for integrating mRNA expression data with microRNA expression data in a Target Bias Analysis by determining the probability that targets of individual miRNAs which were up- or down-regulated would also be dysregulated in HIV infection. Hierarchical clustering showed 4 groups of miRNA`s: A. Those with many dysregulated genes of less stringent significance, B. Those with few dysregulated genes of highly stringent significance, and C. Those with a spectrum from non-bias to combinations of A and B. Interestingly the dysregulated miRNAs also showed chromosomal location clusters on Chrs 14, 17, 19, and X. These observations warrant future investigations into both the mechanisms by which HIV affects CNS miRNA repertoire and the downstream effects of the miRNA changes that occur.

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