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通过深度测序分析大鼠坐骨神经损伤后的 microRNAs 谱:对神经再生机制的启示。

Profile of microRNAs following rat sciatic nerve injury by deep sequencing: implication for mechanisms of nerve regeneration.

机构信息

Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong, China.

出版信息

PLoS One. 2011;6(9):e24612. doi: 10.1371/journal.pone.0024612. Epub 2011 Sep 13.

Abstract

Unlike the central nervous system, peripheral nerves can regenerate when damaged. MicroRNA (miRNA) is a novel class of small, non-coding RNA that regulates gene expression at the post-transcriptional level. Here, we report regular alterations of miRNA expression following rat sciatic nerve injury using deep sequencing. We harvested dorsal root ganglia tissues and the proximal stumps of the nerve, and identified 201 and 225 known miRNAs with significant expression variance at five time points in these tissues after sciatic nerve transaction, respectively. Subsequently, hierarchical clustering, miRNA expression pattern and co-expression network were performed. We screened out specific miRNAs and further obtained the intersection genes through target analysis software (Targetscan and miRanda). Moreover, GO and KEGG enrichment analyses of these intersection genes were performed. The bioinformatics analysis indicated that the potential targets for these miRNAs were involved in nerve regeneration, including neurogenesis, neuron differentiation, vesicle-mediated transport, homophilic cell adhesion and negative regulation of programmed cell death that were known to play important roles in regulating nerve repair. Finally, we combined differentially expressed mRNA with the predicted targets for selecting inverse miRNA-target pairs. Our results show that the abnormal expression of miRNA may contribute to illustrate the molecular mechanisms of nerve regeneration and that miRNAs are potential targets for therapeutic interventions and may enhance intrinsic regenerative ability.

摘要

与中枢神经系统不同,外周神经在受损后可以再生。MicroRNA(miRNA)是一类新型的小非编码 RNA,可在转录后水平调节基因表达。在这里,我们使用深度测序报告了大鼠坐骨神经损伤后 miRNA 表达的规律变化。我们采集背根神经节组织和神经近端残端,并在坐骨神经损伤后五个时间点分别在这些组织中鉴定出 201 个和 225 个已知具有显著表达差异的 miRNA。随后,进行了层次聚类、miRNA 表达模式和共表达网络分析。我们筛选出特定的 miRNA,并通过靶标分析软件(Targetscan 和 miRanda)进一步获得交集基因。此外,对这些交集基因进行了 GO 和 KEGG 富集分析。生物信息学分析表明,这些 miRNA 的潜在靶标参与神经再生,包括神经发生、神经元分化、囊泡介导的运输、同源细胞黏附和程序性细胞死亡的负调控,这些都被认为在调节神经修复中起着重要作用。最后,我们结合差异表达的 mRNA 与预测的靶标,选择了反向 miRNA-靶标对。我们的研究结果表明,miRNA 的异常表达可能有助于阐明神经再生的分子机制,miRNA 是治疗干预的潜在靶点,并可能增强内在的再生能力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4232/3172250/4c3660ca7a3d/pone.0024612.g001.jpg

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