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GATA3-AS1 长非编码 RNA 水平升高与多发性硬化症患者 GATA3 和 IL-4 基因的上调相关。

Increased level of GATA3-AS1 long non-coding RNA is correlated with the upregulation of GATA3 and IL-4 genes in multiple sclerosis patients.

机构信息

Department of Biology, Zarghan Branch, Islamic Azad University, Zarghan, Iran.

Clinical Neurology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.

出版信息

Mol Biol Rep. 2024 Jul 30;51(1):874. doi: 10.1007/s11033-024-09818-6.

DOI:10.1007/s11033-024-09818-6
PMID:39080124
Abstract

BACKGROUND

Long non-coding RNAs (lncRNAs) play various roles in gene regulation. GATA3 antisense RNA 1 (GATA3-AS1) is an lncRNA gene neighboring GATA binding protein 3 (GATA3). The current study aims to quantitatively compare the levels of the expression of GATA3-AS1, GATA3, and Interleukin-4 (IL-4) in peripheral blood mononuclear cells (PBMC) samples of MS patients and healthy individuals under the hypothesis of regulation of GATA3 and IL-4 expression orchestrated by GATA3-AS1.

METHODS AND RESULTS

In this case-control study, the GATA3-AS1, GATA3 and IL-4 expression profiles were assessed using real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). Also, we assessed the IL-4 levels in the serum. The median fold changes in MS patients vs. controls were (4.39 ± 0.38 vs. 2.44 ± 0.20) for GATA3-AS1, (5.22 ± 0.51 vs. 2.86 ± 0.30) for GATA3, and (6.16 ± 0.52 vs. 3.57 ± 0.38) for IL-4, (P < 0.001). Furthermore, the mean serum levels of IL-4 were 30.85 ± 1.53 pg/ml in MS patients and 11.15 ± 4.23 pg/ml in healthy controls (P < 0.001). ROC curve analysis showed that the level of GATA3-AS1 might serve as a biomarker for diagnosing MS patients with the area under the curve (AUC = 0.918, P < 0.0001). Based on our results, this GATA3-AS1/GATA3/IL-4 pathway may increase IL-4 expression in MS patients.

CONCLUSIONS

Our results indicate a probably regulatory function for GATA3-AS1and the levels of GATA3-AS1 in blood could be important biomarkers for MS diagnosis. To confirm and be more certain of these results, it is necessary to study neuromyelitis optica (NMO) and asthma patients in future studies.

摘要

背景

长链非编码 RNA(lncRNA)在基因调控中发挥着多种作用。GATA 结合蛋白 3(GATA3)反义 RNA1(GATA3-AS1)是 GATA3 基因附近的 lncRNA 基因。本研究旨在通过假设 GATA3-AS1 调控 GATA3 和白细胞介素 4(IL-4)的表达,定量比较多发性硬化症(MS)患者和健康个体外周血单个核细胞(PBMC)样本中 GATA3-AS1、GATA3 和 IL-4 的表达水平。

方法和结果

在这项病例对照研究中,采用实时定量逆转录聚合酶链反应(qRT-PCR)评估 GATA3-AS1、GATA3 和 IL-4 的表达谱。此外,我们还评估了血清中的 IL-4 水平。MS 患者与对照组相比,GATA3-AS1 的中位数 fold change 为(4.39±0.38)比(2.44±0.20),GATA3 的中位数 fold change 为(5.22±0.51)比(2.86±0.30),IL-4 的中位数 fold change 为(6.16±0.52)比(3.57±0.38)(P<0.001)。此外,MS 患者的血清 IL-4 平均水平为 30.85±1.53 pg/ml,健康对照组为 11.15±4.23 pg/ml(P<0.001)。ROC 曲线分析显示,GATA3-AS1 水平可能作为 MS 患者诊断的生物标志物,曲线下面积(AUC=0.918,P<0.0001)。根据我们的结果,GATA3-AS1/GATA3/IL-4 通路可能增加 MS 患者的 IL-4 表达。

结论

我们的结果表明,GATA3-AS1 可能具有调节功能,血液中 GATA3-AS1 的水平可能是 MS 诊断的重要生物标志物。为了证实和更确定这些结果,有必要在未来的研究中研究视神经脊髓炎(NMO)和哮喘患者。

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