Table_4_v1_Transcriptomic Analysis of Long Non-coding RNA-MicroRNA-mRNA Interactions in the Nucleus Accumbens Related to Morphine Addiction in Mice.XLS

Recent research suggest that some non-coding RNAs (ncRNAs) are important regulators of chromatin dynamics and gene expression in nervous system development and neurological diseases. Nevertheless, the molecular mechanisms of long non-coding RNAs (lncRNAs), acting as competing endogenous RNAs (ceRNAs), underlying morphine addiction are still unknown. In this research, RNA sequencing (RNA-seq) was used to examine the expression profiles of lncRNAs, miRNAs and mRNAs on the nucleus accumbens (NAc) tissues of mice trained with morphine or saline conditioned place preference (CPP), with differential expression of 31 lncRNAs, 393 miRNAs, and 371 mRNAs found. A ceRNA network was established for reciprocal interactions for 9 differentially expressed lncRNAs (DElncRNAs), 10 differentially expressed miRNAs (DEmiRNAs) and 12 differentially expressed mRNAs (DEmRNAs) based on predicted miRNAs shared by lncRNAs and mRNAs. KEGG pathway enrichment analyses were conducted to explore the potential functions of DEmRNAs interacting with lncRNAs in the ceRNA network. These DEmRNAs were enriched in synaptic plasticity-related pathways, including pyrimidine metabolism, ECM-receptor interaction, and focal adhesion. The correlation between the relative expression of lncRNAs, miRNAs and mRNAs was analyzed to further validate predicted ceRNA networks, and the Lnc15qD3-miR-139-3p-Lrp2 ceRNA regulatory interaction was determined. These results suggest that the comprehensive network represents a new insight into the lncRNA-mediated ceRNA regulatory mechanisms underlying morphine addiction and provide new potential diagnostic and prognostic biomarkers for morphine addiction.

最新研究表明，部分非编码RNA（non-coding RNAs, ncRNAs）是调控神经系统发育及神经疾病中染色质动态变化与基因表达的重要因子。然而，作为内源竞争RNA（competing endogenous RNAs, ceRNAs）发挥功能的长链非编码RNA（long non-coding RNAs, lncRNAs）在吗啡成瘾中的分子机制仍有待阐明。本研究采用RNA测序（RNA sequencing, RNA-seq）技术，检测了经吗啡或生理盐水条件位置偏爱（conditioned place preference, CPP）训练的小鼠伏隔核（nucleus accumbens, NAc）组织中长链非编码RNA、微小RNA（miRNAs）及信使RNA（mRNAs）的表达谱，共筛选得到31个差异表达长链非编码RNA、393个差异表达微小RNA及371个差异表达信使RNA。基于长链非编码RNA与信使RNA共享的微小RNA预测结果，我们构建了包含9个差异表达长链非编码RNA（differentially expressed lncRNAs, DElncRNAs）、10个差异表达微小RNA（differentially expressed miRNAs, DEmiRNAs）及12个差异表达信使RNA（differentially expressed mRNAs, DEmRNAs）的内源竞争RNA调控网络，以解析三者间的相互调控关系。对该网络中与长链非编码RNA存在相互作用的差异表达信使RNA进行KEGG通路富集分析，结果显示这些差异表达信使RNA显著富集于与突触可塑性相关的通路，包括嘧啶代谢、细胞外基质-受体相互作用及黏着斑通路。通过分析长链非编码RNA、微小RNA与信使RNA的相对表达相关性，进一步验证了预测的内源竞争RNA调控网络，并确定了Lnc15qD3-miR-139-3p-Lrp2这一内源竞争RNA调控轴。本研究结果为解析吗啡成瘾中长链非编码RNA介导的内源竞争RNA调控机制提供了全新视角，同时为吗啡成瘾的诊断与预后提供了潜在的新型生物标志物。