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多发性硬化症患者中 NF-κB 相关 lncRNAs 的失调。

Dysregulation of NF-κB-Associated lncRNAs in Multiple Sclerosis Patients.

机构信息

Institute of Research and Development, Duy Tan University, Da Nang, 550000, Viet Nam.

Department of Immunology, Ophthalmology and ENT, School of Medicine, Complutense University, Madrid, Spain.

出版信息

J Mol Neurosci. 2021 Jan;71(1):80-88. doi: 10.1007/s12031-020-01628-2. Epub 2020 Jun 29.

DOI:10.1007/s12031-020-01628-2
PMID:32613554
Abstract

Long non-coding RNAs (lncRNAs) have been reported to participate in the pathogenesis of several complex disorders such as immune-related disorders. Multiple sclerosis (MS) as an inflammatory disorder of the central nervous system has been associated with aberrant expression of several lncRNAs. In the current study, we assessed expression of NF-κB-, autophagy-, and obesity-associated lncRNAs/genes and two inflammatory cytokines in the peripheral blood of MS patients and healthy controls. LNC-MKI67IP was down-regulated in total MS patients compared with total controls (P value < 0.0001). However, when comparing its expression in a gender-based manner, no significant difference was found between patients and controls. Expression of HNF1A-AS1 was significantly lower in total MS patients and patients of both sexes when compared with the matched controls (P value < 0.0001; P value = 0.03; P value = 0.004, respectively). Expression of LINC00305 had a similar pattern to HNF1A-AS1 (P value < 0.0001; P value = 0.005; P value < 0.0001, respectively). Expressions of other assessed NF-κB associated lncRNAs were not different between cases and controls. Expression of IL-1B was significantly lower in total MS patients compared with total controls (P value < 0.0001). Such decreased expression was detected in female patients compared with female controls as well (P value < 0.0001). Expression of IL-6 was not different between cases and controls. Expression of CEBPA was higher in total MS patients compared with controls (P value = 0.047). However, when dividing study participants into male and female subgroups, no significant difference was detected between cases and gender-matched controls. There were no significant difference in the expression of any assessed autophagy-associated lncRNAs between cases and controls. ATG5, CEBPA, HNF1A-AS1, IL-1B, LINC00305, and LNC-MKI67IP could differentiate disease status with diagnostic power values of 0.781, 0.582, 0.744, 0.76, 0.926, and 0.703, respectively. Expression levels of ADINR and CHAST were correlated with age of MS patients and disease duration, respectively (r = 0.33, P < 0.0001; r = 0.34, P < 0.0001, respectively). The present study highlighted the role of a number lncRNAs in the pathogenesis of MS and supported the previous data regarding aberrant expression of these transcripts in this immune-related disorder.

摘要

长非编码 RNA(lncRNA)已被报道参与多种复杂疾病的发病机制,如免疫相关疾病。多发性硬化症(MS)作为一种中枢神经系统的炎症性疾病,与多种 lncRNA 的异常表达有关。在本研究中,我们评估了 MS 患者和健康对照者外周血中 NF-κB、自噬和肥胖相关 lncRNA/基因和两种炎症细胞因子的表达。与总对照组相比,总 MS 患者的 LNC-MKI67IP 表达下调(P 值<0.0001)。然而,当按性别比较其表达时,患者与对照组之间无显著差异。与匹配的对照组相比,MS 患者和各性别患者的 HNF1A-AS1 表达显著降低(P 值<0.0001;P 值=0.03;P 值=0.004,分别)。LINC00305 的表达模式与 HNF1A-AS1 相似(P 值<0.0001;P 值=0.005;P 值<0.0001,分别)。其他评估的 NF-κB 相关 lncRNA 的表达在病例和对照组之间没有差异。与总对照组相比,MS 患者的 IL-1B 表达显著降低(P 值<0.0001)。与女性对照组相比,女性患者的这种表达也降低了(P 值<0.0001)。病例与对照组之间的 IL-6 表达无差异。与对照组相比,MS 患者的 CEBPA 表达升高(P 值=0.047)。然而,当将研究参与者分为男性和女性亚组时,病例与性别匹配的对照组之间没有检测到显著差异。病例与对照组之间任何评估的自噬相关 lncRNA 的表达均无差异。ATG5、CEBPA、HNF1A-AS1、IL-1B、LINC00305 和 LNC-MKI67IP 可以分别以 0.781、0.582、0.744、0.76、0.926 和 0.703 的诊断效能值区分疾病状态。ADINR 和 CHAST 的表达水平与 MS 患者的年龄和疾病持续时间相关(r=0.33,P<0.0001;r=0.34,P<0.0001,分别)。本研究强调了一些 lncRNA 在 MS 发病机制中的作用,并支持了先前关于这些转录本在这种免疫相关疾病中异常表达的研究数据。

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