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血清微小RNA作为人类椎间盘退变生物标志物的鉴定与特征分析:一项RNA测序分析

Identification and Characterization of Serum microRNAs as Biomarkers for Human Disc Degeneration: An RNA Sequencing Analysis.

作者信息

Cui Shangbin, Zhou Zhiyu, Liu Xizhe, Richards Robert Geoff, Alini Mauro, Peng Songlin, Liu Shaoyu, Zou Xuenong, Li Zhen, Grad Sibylle

机构信息

Guangdong Provincial Key Laboratory of Orthopedics and Traumatology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510000, China.

AO Research Institute Davos, 7270 Davos, Switzerland.

出版信息

Diagnostics (Basel). 2020 Dec 8;10(12):1063. doi: 10.3390/diagnostics10121063.

Abstract

Circulating microRNAs (miRNAs) have been associated with various degenerative diseases, including intervertebral disc (IVD) degeneration. Lumbar disc herniation (LDH) often occurs in young patients, although the underlying mechanisms are poorly understood. The aim of this work was to generate RNA deep sequencing data of peripheral blood samples from patients suffering from LDH, identify circulating miRNAs, and analyze them using bioinformatics applications. Serum was collected from 10 patients with LDH (Disc Degeneration Group); 10 patients without LDH served as the Control Group. RNA sequencing analysis identified 73 differential circulating miRNAs ( < 0.05) between the Disc Degeneration Group and Control Group. Gene ontology enrichment analysis ( < 0.05) showed that these differentially expressed miRNAs were associated with extracellular matrix, damage reactions, inflammatory reactions, and regulation of apoptosis. Kyoto Encyclopedia of Genes and Genomes analysis showed that the differentially expressed genes were involved in diverse signaling pathways. The profile of miR-766-3p, miR-6749-3p, and miR-4632-5p serum miRNAs was significantly enriched ( < 0.05) in multiple pathways associated with IVD degeneration. miR-766-3p, miR-6749-3p, and miR-4632-5p signature from serum may serve as a noninvasive diagnostic biomarker for LHD manifestation of IVD degeneration. Furthermore, several dysregulated miRNAs may be involved in the pathogenesis of IVD degeneration. Further study is needed to confirm the functional role of the identified miRNAs.

摘要

循环微RNA(miRNA)已与包括椎间盘(IVD)退变在内的多种退行性疾病相关联。腰椎间盘突出症(LDH)常发生于年轻患者,但其潜在机制尚不清楚。这项工作的目的是生成LDH患者外周血样本的RNA深度测序数据,鉴定循环miRNA,并使用生物信息学应用程序对其进行分析。从10例LDH患者(椎间盘退变组)中采集血清;10例无LDH的患者作为对照组。RNA测序分析在椎间盘退变组和对照组之间鉴定出73种差异循环miRNA(<0.05)。基因本体富集分析(<0.05)表明,这些差异表达的miRNA与细胞外基质、损伤反应、炎症反应和细胞凋亡调节有关。京都基因与基因组百科全书分析表明,差异表达基因参与多种信号通路。miR-766-3p、miR-6749-3p和miR-4632-5p血清miRNA谱在与IVD退变相关的多个途径中显著富集(<0.05)。血清中的miR-766-3p、miR-6749-3p和miR-4632-5p特征可能作为IVD退变LHD表现的非侵入性诊断生物标志物。此外,几种失调的miRNA可能参与IVD退变的发病机制。需要进一步研究来证实所鉴定miRNA的功能作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9041/7762572/04a3a51b4a5e/diagnostics-10-01063-g001.jpg

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