Alzheimer's disease (AD) is the most common cause of dementia. One of the pathological hallmarks of AD is amyloid β (Aβ) deposition. MicroRNAs (miRNAs) are small non-coding RNAs whose expression levels change significantly during neuronal pathogenesis and may be used as diagnostic markers. Some miRNAs are important in AD development by targeting genes responsible for Aβ metabolism. However, a systematic assessment of the miRNA expression profile induced by Aβ-mediated neuronal pathogenesis is still lacking. In the present study, we examined miRNA expression profile by using the APPswe/PS1ΔE9 mouse model of AD. Two sibling pairs of mice were examined, showing 30 and 24 miRNAs with significantly altered expression levels from each paired control, respectively. Nine known miRNAs were common in both groups. Prediction of putative target genes and functional annotation implied that these altered miRNAs affect many target genes mainly involved in PI3K/Akt signaling pathway. This study provides a general profile of miRNAs regulated by Aβ-associated signal pathways, which is helpful to understand the mechanism of Aβ-induced neuronal dysfunction in AD development.
Pin1 (peptidylprolyl cis/trans isomerase, NIMA-interacting 1) plays a key role in a number of diseases including cancer and Alzheimer disease. Previous studies have identified a wide range of phosphoproteins as Pin1 substrates. Related pathways were analyzed separately. The aim of this study was to provide a comprehensive picture involving Pin1 regulation. A genome-wide mRNA expression microarray was carried out using the RNA isolation from Pin1 (+/+) and Pin1 (-/-) mouse embryonic fibroblast (MEF) cells. Signaling pathways regulated by Pin1 were analyzed with the utility of KEGG pathway and GO annotation. An expression pattern regulated by Pin1 was revealed. A total of 606 genes, 375 being up-regulated and 231 down-regulated, were differentially expressed when comparing Pin1 +/+ to Pin1 -/- MEF cells. Totally 48 pathways were shown to be regulated by Pin1 expression in KEGG pathway analysis. In the GO annotation system, 19 processes on biological processes, 15 processes on cellular components, and 18 processes on molecular functions were found to be in the regulation of Pin1 expression. Pathways related to immune system and cancer showed most significant association with Pin1 regulation. Pin1 is an important regulator in a wide range of signaling pathways that were related to immune system and cancer.
HIV-associated neurocognitive disorder (HAND) remains an unresolved issue of cognitive impairment. Due to treatment with combination antiretroviral therapy for nearly two decades, the severe form of HAND is rare, and most cases of HAND are the milder form. However, the proportion of HIV+ individuals with neurocognitive impairment has remained unchanged. Increasing evidence indicates that long noncoding RNAs (lncRNAs) play important roles in the pathogenesis of several types of neurodegenerative disorders. However, there are few relevant reports about the role of lncRNAs in promoting or delaying pathogenesis of HAND. Our study is the first to use the weighted gene co-expression network analysis approach with microarray data from the Gene Expression Omnibus to investigate the functions of lncRNAs that differ significantly between HIV+ patients without neurocognitive impairment and HIV+ patients with neurocognitive disorders. A total of 28 differentially expressed lncRNAs (DE-lncRNAs) were identified including 13 DE-lncRNAs in frontal white matter, 13 DE-lncRNAs in basal ganglia, and 2 DE-lncRNAs in frontal neocortex. Most of these DE-lncRNAs had not been previously reported to be related to HAND. Our coexpression network and function enrichment analysis indicate that DE-lncRNAs should play fundamental roles in HAND development and neurodegeneration associated with synaptic plasticity and synaptogenesis, neuronal inflammation and apoptosis, neurotransmitter transport and metabolism. Although the biological significance of DE-lncRNAs requires further evaluation, our study proposes a simple and efficient strategy to identify important lncRNAs associated with HAND and predict their potential functional roles, which may guide subsequent experimental studies.
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