Genomics

Dataset Information

45

MicroRNAs in the HIV and Major Depressive Brain


ABSTRACT: Micro-RNAs (miRNAs) are small, non-coding RNAs that regulate gene networks, helping to control cell function and phenotype. MiRNAs in the central nervous system (CNS) are considered to be involved in development, function, and homeostasis. Past genomic studies focused on messenger-RNA (mRNA) expression using large-scale hybridization-based arrays 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 perturbations, together in the same clinical specimens. HIV infection affects the CNS through inflammation and glial cell activation leading to long-term changes in cellular function of neurons and glia. One mechanism by which this may occur is through changes in the miRNA repertoire. The goals of this study were to: 1. Identify changes in miRNA expression that occurred in HIV; 2. Determine whether detectable miRNA expression of the frontal cortex (FC) could differentiate HIV from HIV/Major Depressive Disorder (MDD, neurobehavioral diagnostic category); 3. Adapt a method to meaningfully integrate gene expression data and miRNA expression data in clinical samples. The present study was performed by pooling RNA isolated from the FC of 3 patients from each of three groups: Control, HIV+, and HIV/MDD, and assessing miRNA expression profile using Applied Biosystems Taqman MicroRNA Array v2.0. A larger sample size of 4 HIV+ patients and 4 HIV/MDD patients were used and non-pooled for gene expression analysis on Affymetrix U133 Plus 2.0 array. We present a method for integrating the two datasets in a Target Bias Analysis. Micro-RNAs were clustered into three types: A) Those with many dysregulated mRNA targets of less stringent significance; B) Fewer dysregulated target-genes of highly stringent significance; C) Spectrum from non-bias to combinations of A and B. In HIV/MDD, more miRNAs were down-regulated than in HIV alone. The dysregulated miRNAs clustered on Chromosomes 14, 17, 19, and X. A small subset of dysregulated genes had many 3’UTR target-sites for dysregulated miRNAs. Specific miRNA families at targeted chromosomal loci are dysregulated. Certain miRNAs serve as key circuits in gene regulatory networks in the adult human brain, and this is affected by HIV, and may be implicated in neurobehavioral disorder. Some genes may serve as hubs of miRNA activity. Overall design: Retrospective microRNA expression analysis of autopsy brain tissue. Three HIV/MDD and three HIV-only subjects without neuropsychiatric conditions are identified and three age-matched Control subjects are compared. Technical triplicates are performed.

INSTRUMENT(S): Applied Biosystems Human Taqman MicroRNA Array v2.0

SUBMITTER: Erick T Tatro  

PROVIDER: GSE17486 | GEO | 2010-02-01

SECONDARY ACCESSION(S): PRJNA123625

REPOSITORIES: GEO

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Publications

Evidence for Alteration of Gene Regulatory Networks through MicroRNAs of the HIV-infected brain: novel analysis of retrospective cases.

Tatro Erick T ET   Scott Erick R ER   Nguyen Timothy B TB   Salaria Shahid S   Banerjee Sugato S   Moore David J DJ   Masliah Eliezer E   Achim Cristian L CL   Everall Ian P IP  

PloS one 20100426 4


HIV infection disturbs the central nervous system (CNS) through inflammation and glial activation. Evidence suggests roles for microRNA (miRNA) in host defense and neuronal homeostasis, though little is known about miRNAs' role in HIV CNS infection. MiRNAs are non-coding RNAs that regulate gene translation through post-transcriptional mechanisms. Messenger-RNA profiling alone is insufficient to elucidate the dynamic dance of molecular expression of the genome. We sought to clarify RNA alteration  ...[more]

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