Identification of lncRNA expression profiles and ceRNA analysis in the spinal cord of morphine-tolerant rats.

Identification of lncRNA expression profiles and ceRNA analysis in the spinal cord of morphine-tolerant rats.
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吗啡耐受大鼠脊髓中lncRNA表达谱的鉴定和ceRNA分析

DOI:
10.1186/s13041-018-0365-8
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发表时间:
2018-04-10
期刊:
影响因子:
3.6
通讯作者:
Zou W
Zou W
中科院分区:
医学3区
文献类型:
--
作者:
Shao J;Wang J;Huang J;Liu C;Pan Y;Guo Q;Zou W

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吗啡耐受是一个具有挑战性的临床问题,限制了吗啡在疼痛治疗中的使用,但吗啡耐受的机制尚不清楚。最近的研究表明,长非编码RNA(LncRNAs)可能是疾病发病机制中一个新的、有前途的靶点。因此,我们推测lncRNAs可能在吗啡耐受的形成中起作用。雄性SD大鼠鞘内注射10μg吗啡,每日2次,连续7天。然后处死动物进行LncRNA微阵列测试,结果通过RT-qPCR进行验证。然后,利用基因本体论/京都基因和基因组百科全书(GO/KEGG)对差异表达的mRNAs(DEmRNAs)进行功能预测,并基于竞争性内源RNA(CERNA)分析对差异表达的LncRNAs(DElncRNAs)进行预测。这些大鼠成功地产生了吗啡耐受性。LncRNA芯片分析显示,以 > 1.5和AP-Value< 0.0 5为标准,吗啡耐受组(MT)与生理盐水组(NS)相比有136个和2 78个mRNAs表达差异。DEmRNAs的功能可能参与离子通道运输、疼痛传递和免疫反应等过程。CERNA分析表明存在几个可能的相互作用网络,包括(MRAK150340,MRAK161211)/miR-219b/Tollip.进一步根据基因数据库对miRNAs的潜在靶向mRNAs进行注释,表明这些mRNAs可能的功能主要涉及泛素化、G蛋白相关受体和Toll样受体的调节,这些受体在吗啡耐受的形成中发挥作用。我们的发现揭示了在吗啡耐受条件下差异表达的lncRNAs的图谱,其中一些DElncRNAs可能成为吗啡耐受的新的治疗靶点。
Morphine tolerance is a challenging clinical problem that limits the use of morphine in pain treatment, but the mechanisms of morphine tolerance remain unclear. Recent research indicates that long noncoding RNAs (lncRNAs) might be a novel and promising target in the pathogeneses of diseases. Therefore, we hypothesized that lncRNAs might play a role in the development of morphine tolerance. Male Sprague-Dawley rats were intrathecally injected with 10 μg morphine twice daily for 7 consecutive days. The animals were then sacrificed for lncRNA microarray tests, and the results were validated by RT-qPCR. Next, functional predictions for the differentially expressed mRNAs (DEmRNAs) were made with the Gene Ontology/Kyoto Encyclopedia of Genes and Genomes (GO/KEGG), and predictions for the differentially expressed lncRNAs (DElncRNAs) were made based on competitive endogenous RNA (ceRNA) analyses. The rats successfully developed morphine tolerance. LncRNA microarray analysis revealed that, according to the criteria of a log2 (fold change) > 1.5 and aP-value < 0.05, 136 lncRNAs and 278 mRNAs were differentially expressed in the morphine tolerance group (MT) compared with the normal saline group (NS). The functions of the DEmRNAs likely involve in the processes of the ion channel transport, pain transmission and immune response. The ceRNA analysis indicated that several possible interacting networks existed, including (MRAK150340, MRAK161211)/miR-219b/Tollip.Further annotations of the potential target mRNAs of the miRNAs according to the gene database suggested that the possible functions of these mRNAs primarily involved the regulation of ubiquitylation, G protein-linked receptors, and Toll-like receptors, which play roles in the development of morphine tolerance. Our findings revealed the profiles of differentially expressed lncRNAs in morphine tolerance conditions, and among these lncRNAs, some DElncRNAs might be new therapeutic targets for morphine tolerance.
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