WITHDRAWN: Exploring functions of long non-coding RNAs in HIV-associated neurocognitive disorder through weighted gene co-expression network analysis

Abstract

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.