中国西北汉族人群骨关节炎软骨细胞中与细胞周期相关的长链非编码RNA和信使核糖核酸

Cell cycle-related lncRNAs and mRNAs in osteoarthritis chondrocytes in a Northwest Chinese Han Population.

作者信息

Zhang Feng'e, Lammi Mikko Juhani, Tan Sijia, Meng Peilin, Wu Cuiyan, Guo Xiong

机构信息

School of Public Health, Health Science Center of Xi'an Jiaotong University.

Collaborative Innovation Center of Endemic Diseases and Health Promotion for Silk Road Region of Shaanxi Province.

出版信息

Medicine (Baltimore). 2020 Jun 12;99(24):e19905. doi: 10.1097/MD.0000000000019905.

Abstract

BACKGROUND

A group of differentially expressed long non-coding RNAs (lncRNAs) have been shown to play key roles in osteoarthritis (OA), although they represented only a small proportion of lncRNAs that may be biologically and physiologically relevant. Since our knowledge of regulatory functions of non-coding RNAs is still limited, it is important to gain better understanding of their relation to the pathogenesis of OA.

METHODS

We performed mRNA and lncRNA microarray analysis to detect differentially expressed RNAs in chondrocytes from three OA patients compared with four healthy controls. Then, enrichment analysis of the differentially expressed mRNAs was carried out to define disease molecular networks, pathways and gene ontology (GO) function. Furthermore, target gene prediction based on the co-expression network was performed to reveal the potential relationships between lncRNAs and mRNAs, contributing an exploration of a role of lncRNAs in OA mechanism. Quantitative RT-PCR analyses were used to demonstrate the reliability of the experimental results.

FINDINGS

Altogether 990 lncRNAs (666 up-regulated and 324 down-regulated) and 546 mRNAs (419 up-regulated and 127 down-regulated) were differentially expressed in OA samples compared with the normal ones. The enrichment analysis revealed a set of genes involved in cell cycle. In total, 854 pairs of mRNA and lncRNA were highly linked, and further target prediction appointed 12 genes specifically for their corresponding lncRNAs. The lncRNAs lncRNA-CTD-2184D3.4, ENST00000564198.1, and ENST00000520562.1 were predicted to regulate SPC24, GALM, and ZNF345 mRNA expressions in OA.

INTERPRETATION

This study uncovered several novel genes potentially important in pathogenesis of OA, and forecast the potential function of lnc-CTD-2184D3.4, especially for the cell cycle in the chondrocytes. These findings may promote additional aspects in studies of OA.

摘要

背景

一组差异表达的长链非编码RNA(lncRNA)已被证明在骨关节炎(OA)中起关键作用,尽管它们仅占可能具有生物学和生理学相关性的lncRNA的一小部分。由于我们对非编码RNA调控功能的了解仍然有限,因此更好地了解它们与OA发病机制的关系非常重要。

方法

我们进行了mRNA和lncRNA微阵列分析,以检测三名OA患者与四名健康对照的软骨细胞中差异表达的RNA。然后,对差异表达的mRNA进行富集分析,以确定疾病分子网络、途径和基因本体(GO)功能。此外,基于共表达网络进行靶基因预测,以揭示lncRNA与mRNA之间的潜在关系,有助于探索lncRNA在OA机制中的作用。定量RT-PCR分析用于验证实验结果的可靠性。

结果

与正常样本相比,OA样本中共有990个lncRNA(666个上调和324个下调)和546个mRNA(419个上调和127个下调)差异表达。富集分析揭示了一组参与细胞周期的基因。总共854对mRNA和lncRNA高度相关,进一步的靶标预测指定了12个基因专门对应其相应的lncRNA。lncRNA lncRNA-CTD-2184D3.4、ENST00000564198.1和ENST00000520562.1被预测在OA中调节SPC24、GALM和ZNF345 mRNA的表达。

解读

本研究发现了几个在OA发病机制中可能重要的新基因,并预测了lnc-CTD-2184D3.4的潜在功能,特别是对软骨细胞中的细胞周期。这些发现可能会推动OA研究的其他方面。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce40/7302618/4783c4ccd459/medi-99-e19905-g001.jpg

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