Abstract

Gene expression and posttranscriptional regulation have been considered to play specific roles in heroin-induced compulsive seeking behavior and drug use. However, the roles of microRNAs (miRNAs), which are common posttranscriptional factors, in the molecular mechanisms of heroin addiction have received relatively little attention. In this study, microarray-based miRNA expression profiling was performed to investigate the deregulated miRNAs associated with heroin addiction in a self-administration paradigm. Furthermore, multiple algorithms for predicting the miRNA-binding sites identified numerous messenger RNA targets (n = 316) interacted with 27 differentially expressed miRNAs. Gene-set enrichment analysis identified 48 significantly overrepresented Gene Ontology terms, some of which were closely associated with neuronal network-related functions, including nervous system development, neuron projection, and negative regulation of synaptic transmission. These findings reveal the perturbed miRNAs in heroin self-administering rats and their interactions with related targets, providing novel insights into related molecular transcriptional regulation mechanisms and identifying promising candidates for clinical therapies against heroin addiction.

中文翻译：

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海洛因自我给药对大鼠脑中 microRNA 表达谱的全局影响

摘要

基因表达和转录后调控被认为在海洛因诱导的强迫性寻求行为和吸毒中发挥特定作用。然而，作为常见的转录后因子的微小RNA（miRNA）在海洛因成瘾的分子机制中的作用相对较少受到关注。在这项研究中，进行了基于微阵列的 miRNA 表达谱分析，以在自我管理范式中研究与海洛因成瘾相关的失调 miRNA。此外，用于预测 miRNA 结合位点的多种算法确定了许多信使 RNA 目标（n= 316) 与 27 种差异表达的 miRNA 相互作用。基因集富集分析确定了 48 个显着过度表达的 Gene Ontology 术语，其中一些与神经元网络相关功能密切相关，包括神经系统发育、神经元投射和突触传递的负调节。这些发现揭示了海洛因自我给药大鼠中受干扰的 miRNA 及其与相关靶标的相互作用，为相关分子转录调控机制提供了新的见解，并确定了针对海洛因成瘾的临床治疗的有希望的候选者。