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Potential Biomarker and Therapeutic LncRNAs in Multiple Sclerosis Through Targeting Memory B Cells
Archives of Computational Methods in Engineering ( IF 9.7 ) Pub Date : 2019-10-01 , DOI: 10.1007/s12017-019-08570-6
Elahe Ghoveud , Shohreh Teimuri , Jafar Vatandoost , Aref Hosseini , Kamran Ghaedi , Masood Etemadifar , Mohammad Hossein Nasr Esfahani , Timothy L. Megraw

Abstract

Multiple sclerosis (MS) is a chronic autoimmune disease that degenerates the central nervous system (CNS). B cells exacerbate the progression of CNS lesions in MS by producing auto-antibodies, pro-inflammatory cytokines, and presenting auto-antigens to activated T cells. Long non-coding RNAs (lncRNAs) play a crucial role in complex biological processes and their stability in body fluids combined with their tissue specificity make these biomolecules promising biomarker candidates for MS diagnosis. In the current study, we investigated memory B cell-specific lncRNAs located, on average, less than 50 kb from differentially expressed protein-coding genes in MS patients compared to healthy individuals. Moreover, we included in our selection criteria lncRNA transcripts predicted to interact with microRNAs with established involvement in MS. To assess the expression levels of lncRNAs and their adjacent protein-coding genes, quantitative reverse transcription PCR was performed on peripheral blood mononuclear cells samples of 50 MS patients compared to 25 controls. Our results showed that in relapsing MS patients, compared to remitting MS patients and healthy controls, lncRNA RP11-530C5.1 was up-regulated while AL928742.12 was down-regulated. Pearson’s correlation tests showed positive correlations between the expression levels of RP11-530C5.1 and AL928742.12 with PAWR and IGHA2, respectively. The results of the ROC curve test demonstrated the potential biomarker roles of AL928742.12 and RP11-530C5.1. We conclude that these lncRNAs are potential markers for detection of relapsing MS patients.



中文翻译:

通过靶向记忆B细胞在多发性硬化症中潜在的生物标志物和治疗性LncRNAs

摘要

多发性硬化症(MS)是一种慢性自身免疫性疾病,会导致中枢神经系统(CNS)退化。B细胞通过产生自身抗体,促炎性细胞因子并对激活的T细胞呈递自身抗原,从而加剧了MS中CNS病变的发展。长的非编码RNA(lncRNA)在复杂的生物过程中起着至关重要的作用,它们在体液中的稳定性以及它们的组织特异性使这些生物分子有望成为MS诊断的候选生物标记。在当前的研究中,我们调查了与健康个体相比,MS患者中记忆B细胞特异的lncRNA平均距离差异表达蛋白编码基因不到50 kb。此外,我们在选择标准中包括了预测与已确定参与MS的microRNA相互作用的lncRNA转录本。为了评估lncRNA及其邻近蛋白编码基因的表达水平,对50名MS患者的外周血单核细胞样品与25名对照进行了定量逆转录PCR。我们的结果表明,与复发型MS患者和健康对照组相比,复发型MS患者中lncRNA RP11-530C5.1上调而AL928742.12下调。皮尔森相关性测试显示RP11-530C5.1和AL928742.12的表达水平之间存在正相关。lncRNA RP11-530C5.1被上调,而AL928742.12被下调。皮尔森相关性测试显示RP11-530C5.1和AL928742.12的表达水平之间存在正相关。lncRNA RP11-530C5.1被上调,而AL928742.12被下调。皮尔森相关性测试显示RP11-530C5.1和AL928742.12的表达水平之间存在正相关。PAWRIGHA2分别。ROC曲线测试的结果证明了AL928742.12和RP11-530C5.1的潜在生物标志物作用。我们得出的结论是,这些lncRNAs是检测复发性MS患者的潜在标志物。

更新日期:2020-03-26
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