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膝关节骨关节炎患者软骨中长链非编码RNA的表达谱

Expression profile of long noncoding RNAs in cartilage from knee osteoarthritis patients.

作者信息

Fu M, Huang G, Zhang Z, Liu J, Zhang Z, Huang Z, Yu B, Meng F

机构信息

Department of Joint Surgery, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China.

Department of Joint Surgery, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China.

出版信息

Osteoarthritis Cartilage. 2015 Mar;23(3):423-32. doi: 10.1016/j.joca.2014.12.001. Epub 2014 Dec 15.

Abstract

OBJECTIVES

Long noncoding RNAs (lncRNAs) have emerged as a novel class of regulatory molecules involved in various biological processes, but their role in osteoarthritis (OA) remains unknown. Therefore, we aimed to reveal lncRNAs expression profile in human osteoarthritic cartilage and explore the potential functions of lncRNAs in OA.

METHODS

The expression profiles of lncRNAs and mRNAs in OA cartilage were obtained using microarray and verified by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Bioinformatics analyses including lncRNA classification and subgroup analysis, gene ontology (GO) analysis, pathway analysis, network analysis and target prediction were performed.

RESULTS

There were 3007 upregulated lncRNAs and 1707 downregulated lncRNAs in OA cartilage compared with normal samples (Fold change ≥ 2.0). In addition, 2136 mRNAs were upregulated and 2,241 mRNAs were downregulated in OA cartilage (Fold change ≥ 2.0). The qRT-PCR results of six dysregulated lncRNAs were consistent with the microarray data. 106 lncRNAs and 291 mRNAs composed the coding-non-coding gene co-expression network (CNC network). In the 600 top differentially expressed lncRNAs, 48 lncRNAs were predicted to have more than five cis-regulated target genes and up to 530 lncRNAs might regulate their trans target genes through collaboration with transcriptional factor (TF) SP1. The positive correlation between lncRNA uc.343 and predicted target homeobox gene C8 (HOXC8) expression in SW1353 cells treating with interleukin-1 beta confirmed the target prediction to some extent.

CONCLUSIONS

This study revealed the expression pattern of lncRNAs in OA cartilage and predicted the potential function and targets, which indicated that lncRNAs may be new biomarkers for diagnosis or novel therapeutic targets of OA.

摘要

目的

长链非编码RNA(lncRNAs)已成为一类参与多种生物学过程的新型调节分子,但其在骨关节炎(OA)中的作用仍不清楚。因此,我们旨在揭示人骨关节炎软骨中lncRNAs的表达谱,并探索lncRNAs在OA中的潜在功能。

方法

使用微阵列获得OA软骨中lncRNAs和mRNAs的表达谱,并通过定量逆转录聚合酶链反应(qRT-PCR)进行验证。进行了生物信息学分析,包括lncRNA分类和亚组分析、基因本体(GO)分析、通路分析、网络分析和靶标预测。

结果

与正常样本相比,OA软骨中有3007个上调的lncRNAs和1707个下调的lncRNAs(倍数变化≥2.0)。此外,OA软骨中有2136个mRNAs上调,2241个mRNAs下调(倍数变化≥2.0)。6个失调lncRNAs的qRT-PCR结果与微阵列数据一致。106个lncRNAs和291个mRNAs组成了编码-非编码基因共表达网络(CNC网络)。在600个差异表达最显著的lncRNAs中,预测有48个lncRNAs具有5个以上的顺式调控靶基因,多达530个lncRNAs可能通过与转录因子(TF)SP1协作来调控其反式靶基因。在白细胞介素-1β处理的SW1353细胞中,lncRNA uc.343与预测的靶同源框基因C8(HOXC8)表达之间的正相关在一定程度上证实了靶标预测。

结论

本研究揭示了OA软骨中lncRNAs的表达模式,并预测了其潜在功能和靶标,这表明lncRNAs可能是OA诊断的新生物标志物或新的治疗靶点。

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