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Chunk #29 — 3. Biological co-expression networks: Transcriptional regulation in alcohol use disorder — 3.2: MicroRNAs as transcriptional regulators

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Gene expression profiling in the human alcoholic brain.
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Differentially expressed miRNAs have also been found in the nucleus accumbens of human alcoholics (Mamdani et al., 2015). Although the functional classification of the predicted target genes of the alcohol-responsive miRNAs was similar to those found in the frontal cortex (e.g. cell-adhesion, synaptic transmission, neuronal function), very few of the miRNA hub genes overlapped among brain regions (Lewohl et al., 2011; Mamdani et al., 2015). Only miR-34c-5p was up-regulated in both the cortex and nucleus accumbens (Lewohl et al., 2011; Mamdani et al., 2015). Many of the miRNA targets in the frontal cortex or nucleus accumbens have been implicated in neurodegenerative disorders, such as Alzheimer’s and Parkinson’s diseases (Minones-Moyano et al., 2011; Saito and Saito, 2012). In the frontal cortex, an inverse relationship was detected between a subset of 27 down-regulated mRNA targets and up-regulated genes involved in Alzheimer’s disease (Lewohl et al., 2011). In the nucleus accumbens, down-regulation of the mir-34b/c family was observed (Mamdani et al., 2015). Dysregulation of miR-34b/c triggered downstream transcriptome alterations underlying mitochondrial dysfunction and oxidative stress in Parkinson’s disease, which ultimately compromised cell viability