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Publication Abstract Display
Type: Published Abstract
Title: Alterations of gene regulatory networks through microRNAs in the frontal cortex of HIV-infected individuals.
Authors: Tatro ET, Scott ER, Nguyen TL, Masliah E, Everall IP, Achim CL
Year: 2009
Publication: 9th International Symposium on Neurovirology, Miami, Florida
Volume: 15 Issue: S1 Pages:
Abstract:Background: MicroRNAs are small, non-coding RNAs that regulate gene networks, helping control cell function and phenotype. MicroRNAs are recognized as key players in CNS patterning, function, and disease. Past studies focused on expression levels of coding mRNAs in the brain of HIV-infected individuals. Because microRNAs affect the abundance and downstream functions of mRNAs, it is important to understand both mRNA and miRNA changes concurrently. We report the first genome-wide microRNA profile in the HIV-infected human frontal cortex. We present methods to integrate mRNA expression with microRNA expression data in a Target Bias Analysis by determining the probability that the number of target-genes of dysregulated miRNAs would be dysregulated in HIV infection versus expected by chance. Methods: We used Affymetrix arrays for comparing gene expression in frontal cortex from 6 HIV-infected males (no cognitive impairment or encephalitis) and 6 age-matched controls at the mRNA level. We pooled equivalent RNA samples and utilized Applied Biosystems PCR-based array to assess a panel of 379 microRNAs. Results: Target bias analysis indicated that microRNAs clustered into four 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. The dysregulated miRNAs clustered on Chromosomes 14, 17, 19, and X. Those miRNAs that affect many genes may be important "circuits" in gene regulatory networks pertinent to the effects of HIV infection in CNS. These may be functional and diagnostic markers of neurologic disease in HIV-infected patients.

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