Altered expression of circulating microRNA in plasma of patients with primary osteoarthritis and in silico analysis of their pathways.
Altered expression of circulating microRNA in plasma of patients with primary osteoarthritis and in silico analysis of their pathways.
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DOI：
10.1371/journal.pone.0097690
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Miranda-Duarte A
中科院分区：
文献类型：
--
作者：
Borgonio Cuadra VM;González-Huerta NC;Romero-Córdoba S;Hidalgo-Miranda A;Miranda-Duarte A
分析原发性骨关节炎（OA）患者血浆中的一组循环microRNA (miRNA)，并基于其靶基因的计算机分析描述OA中改变的miRNA的生物学意义。采用TaqMan低密度阵列和独立检测分析miRNA表达。通过miRWalk和miRecords数据库搜索差异表达miRNA的潜在信使RNA （mRNA）靶点；通过Reactome和DAVID数据库的通路分析，我们对预测的miRNA靶点进行了生物学相关性分析。我们在OA中检测了380个miRNA的表达；OA条件下有12个miRNA过表达（p值≤0.05；倍增变化，>2）。这些结果通过定量PCR （qPCR）检测部分选定的miRNA得到验证。计算机分析显示靶信使RNA （mRNA）可能受到这些miRNA的调控，包括SMAD1、IL-1B、COL3A、VEGFA和FGFR1等基因，这些基因在软骨细胞维持和分化中很重要。受miRNA: mRNA比值影响的代谢途径包括骨形态发生蛋白（BMP）、血小板衍生生长因子（PDGF）和神经生长因子（NGF）信号通路，后两者参与疼痛过程。我们在原发性OA患者的血浆中发现了12种miRNA。由于软骨损伤或固有的细胞机制，在疾病中发生改变的特异性miRNA可能被释放到血浆中。几种miRNA可以调控与疾病发展相关的基因和通路；据我们所知，在OA中首次描述了其中8种循环miRNA。
To analyze a set of circulating microRNA (miRNA) in plasma from patients with primary Osteoarthritis (OA) and describe the biological significance of altered miRNA in OA based on an in silico analysis of their target genes. miRNA expression was analyzed using TaqMan Low Density Arrays and independent assays. The search for potential messenger RNA (mRNA) targets of the differentially expressed miRNA was performed by means of the miRWalk and miRecords database; we conducted the biological relevance of the predicted miRNA targets by pathway analysis with the Reactome and DAVID databases. We measured the expression of 380 miRNA in OA; 12 miRNA were overexpressed under the OA condition (p value, ≤0.05; fold change, >2). These results were validated by the detection of some selected miRNA by quantitative PCR (qPCR). In silico analysis showed that target messenger RNA (mRNA) were potentially regulated by these miRNA, including genes such as SMAD1, IL-1B, COL3A, VEGFA, and FGFR1, important in chondrocyte maintenance and differentiation. Some metabolic pathways affected by the miRNA: mRNA ratio are signaling Bone morphogenetic proteins (BMP), Platelet-derived growth factor (PDGF), and Nerve growth factor (NGF), these latter two involved in the process of pain. We identified 12 miRNA in the plasma of patients with primary OA. Specific miRNA that are altered in the disease could be released into plasma, either due to cartilage damage or to an inherent cellular mechanism. Several miRNA could regulate genes and pathways related with development of the disease; eight of these circulating miRNA are described, to our knowledge, for first time in OA.
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影响因子：
5.3
作者：
Liu, Gang;Keeler, Benjamin E.;Zhukareva, Victoria;Houle, John D.
通讯作者：
Houle, John D.
影响因子：
4.9
作者：
Felson DT
通讯作者：
Felson DT
影响因子：
2.3
作者：
Díaz-Prado S;Cicione C;Muiños-López E;Hermida-Gómez T;Oreiro N;Fernández-López C;Blanco FJ
通讯作者：
Blanco FJ
影响因子：
14.9
作者：
Griffiths-Jones, S
通讯作者：
Griffiths-Jones, S
影响因子：
--
作者：
Akhtar, Nahid;Rasheed, Zafar;Ramamurthy, Sangeetha;Anbazhagan, Arivarasu N.;Voss, Frank R.;Haqqi, Tariq M.
通讯作者：
Haqqi, Tariq M.