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多发性硬化症患者中长非编码 RNA 及其靶基因的表达分析。

Expression analysis of long non-coding RNAs and their target genes in multiple sclerosis patients.

机构信息

Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, PO Box 1985717443, Tehran, Iran.

出版信息

Neurol Sci. 2019 Apr;40(4):801-811. doi: 10.1007/s10072-019-3720-3. Epub 2019 Jan 24.

DOI:10.1007/s10072-019-3720-3
PMID:30680474
Abstract

Multiple sclerosis (MS) is a progressive chronic autoimmune-mediated disease. Recently, long non-coding RNAs (lncRNAs) are characterized to participate in the adjustment of immune responses. Here, we evaluated the expression levels of GSTT1-AS1 and IFNG-AS1 lncRNAs and their targets (TNF and IFNG, respectively) in Iranian MS patients.In this case-control study, 50 relapsing-remitting MS patients and 50 healthy subjects were recruited. Expressions of GSTT1-AS1 and IFNG-AS1 lncRNAs, as well as TNF and IFNG genes, were assessed in their peripheral blood samples by SYBR Green-based Real-time quantitative PCR.Expression levels of GSTT1-AS1 and IFNG-AS1 lncRNAs were both significantly downregulated (p values 0.032 and 0.013, respectively). On the other hand, the expression of TNF and IFNG showed increased levels, however, did not reach statistical significance after our analysis (p > 0.05). Spearman correlation analysis showed that GSTT1-AS1 had a significant positive moderate correlation with IFNG-AS1 (r = 0.541, p < 0.0001), IFNG (r = 0.329, p = 0.001), and TNF (r = 0.204, p = 0.041). Also, IFNG-AS1 revealed the same correlation with IFNG (r = 0.475, p < 0.0001) as well as TNF (r = 0.399, p < 0.0001). Furthermore, GSTT1-AS1 (r = 0.313, p = 0.027) and (IFNG r = 0.478, p < 0.0001) demonstrated a significant positive correlation with age at onset.Briefly, the current study provided for the first time dysregulation of GSTT1-AS1 and IFNG-AS lncRNAs network in MS, which highlights the significant role of epigenetic pathways in this autoimmune disorder. Larger sample size and further investigation assays could shed light on the underlying mechanisms in this area of science.

摘要

多发性硬化症(MS)是一种进行性慢性自身免疫介导的疾病。最近,长链非编码 RNA(lncRNA)的特征在于参与免疫反应的调节。在这里,我们评估了 GSTT1-AS1 和 IFNG-AS1 lncRNAs 及其靶标(分别为 TNF 和 IFNG)在伊朗 MS 患者中的表达水平。

在这项病例对照研究中,招募了 50 名复发缓解型 MS 患者和 50 名健康对照者。通过 SYBR Green 基于实时定量 PCR 评估 GSTT1-AS1 和 IFNG-AS1 lncRNAs 以及 TNF 和 IFNG 基因在其外周血样本中的表达水平。 GSTT1-AS1 和 IFNG-AS1 lncRNAs 的表达水平均显著下调(p 值分别为 0.032 和 0.013)。另一方面,TNF 和 IFNG 的表达水平升高,但经我们分析后未达到统计学意义(p>0.05)。Spearman 相关性分析表明,GSTT1-AS1 与 IFNG-AS1(r=0.541,p<0.0001)、IFNG(r=0.329,p=0.001)和 TNF(r=0.204,p=0.041)呈显著正相关。此外,IFNG-AS1 与 IFNG(r=0.475,p<0.0001)和 TNF(r=0.399,p<0.0001)也呈相同的相关性。此外,GSTT1-AS1(r=0.313,p=0.027)和(IFNG r=0.478,p<0.0001)与发病年龄呈显著正相关。

总之,本研究首次提供了 MS 中 GSTT1-AS1 和 IFNG-AS lncRNA 网络失调的证据,突出了表观遗传途径在这种自身免疫性疾病中的重要作用。更大的样本量和进一步的研究检测可能会揭示该科学领域的潜在机制。

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本文引用的文献

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[Diagnosis of multiple sclerosis: A review of the 2017 revisions of the McDonald criteria].[多发性硬化症的诊断:2017年麦克唐纳标准修订版综述]
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Mechanisms of Long Non-Coding RNAs in the Assembly and Plasticity of Neural Circuitry.长非编码 RNA 在神经回路组装和可塑性中的作用机制。
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Expression Analysis of Long Non-coding RNAs in the Blood of Multiple Sclerosis Patients.
长链非编码RNA在免疫系统中的生物学功能及受影响的信号通路。
Noncoding RNA Res. 2024 Sep 6;10:70-90. doi: 10.1016/j.ncrna.2024.09.001. eCollection 2025 Feb.
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The function of long non-coding RNA IFNG-AS1 in autoimmune diseases.长链非编码RNA IFNG-AS1在自身免疫性疾病中的作用。
Hum Cell. 2024 Sep;37(5):1325-1335. doi: 10.1007/s13577-024-01103-9. Epub 2024 Jul 14.
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Non-coding RNAs in immunoregulation and autoimmunity: Technological advances and critical limitations.非编码 RNA 在免疫调节和自身免疫中的作用:技术进展与关键限制
J Autoimmun. 2023 Jan;134:102982. doi: 10.1016/j.jaut.2022.102982. Epub 2022 Dec 31.
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Long Non-Coding RNAs, Novel Offenders or Guardians in Multiple Sclerosis: A Scoping Review.长链非编码 RNA:多发性硬化症中的新型罪犯或守护者:范围综述。
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Scavenging the hidden impacts of non-coding RNAs in multiple sclerosis.清除非编码RNA在多发性硬化症中的潜在影响。
Noncoding RNA Res. 2021 Dec 7;6(4):187-199. doi: 10.1016/j.ncrna.2021.12.002. eCollection 2021 Dec.
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Dysregulation of long noncoding RNA MEG3 and NLRC5 expressions in patients with relapsing-remitting multiple sclerosis: is there any correlation?复发缓解型多发性硬化症患者中长链非编码RNA MEG3和NLRC5表达失调:是否存在相关性?
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