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干扰素 β 和那他珠单抗对复发缓解型多发性硬化症患者 miR-20b 表达的影响可能是通过调节 Jak-STAT 信号通路介导的:一项病例对照研究。

The Effect of Interferon Beta and Natalizumab on miR-20b Expression in Patients with Relapsing-Remitting Multiple Sclerosis is Potentially Mediated by Modulation of the Jak-STAT Signaling Pathway: A Case-control Study.

机构信息

Department of Medical Genetics, Institute of Medical Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran.

Fetal Health Research Center, Hope Generation Foundation, Tehran, Iran.

出版信息

Iran J Immunol. 2024 Jun 30;21(2):158-165. doi: 10.22034/iji.2024.100500.2694. Epub 2024 May 18.

Abstract

BACKGROUND

The mechanisms of the function of interferon beta (IFN-β) and natalizumab (NTZ) in multiple sclerosis (MS) patients have not yet been fully understood. Over the past decades, many studies have been conducted to evaluate gene expression changes especially regulatory non-coding RNAs such as microRNAs (miRNAs) following therapy in MS patients.

OBJECTIVE

To assess the changes in the expression of miR-20b in MS patients treated with IFN-β or NTZ.

METHODS

Sixty patients with relapsing-remitting MS (RRMS) and 30 healthy controls (HCs) were enrolled. The patients were categorized as untreated (N=20), IFN-β-treated (N=20), and NTZtreated (N=20). For the expression analysis, real-time PCR was performed on the whole blood. The bioinformatic tools were applied for signaling pathways enrichment analysis of miR-20b targetome.

RESULTS

The relative expression of miR-20b was significantly downregulated in the untreated patients compared with the HCs (-1.726-fold, p<0.001), while IFN-β-treated and NTZ-treated patients showed no statistical difference compared with the HCs (0.733-fold, p=0.99 for IFN-β and 1.025-fold, p=0.18 for NTZ). This indicates the restoration of miR-20b expression to normal level in the treated patients. Additionally, in silico analysis demonstrated that the Jak-STAT signaling pathway is enriched with miR-20b targets (p<0.0001).

CONCLUSION

Our findings suggest that the positive effects of IFN-β and NTZ in the RRMS patients could be potentially mediated by returning miR-20b expression to baseline.

摘要

背景

干扰素 β(IFN-β)和那他珠单抗(NTZ)在多发性硬化症(MS)患者中的作用机制尚未完全阐明。在过去的几十年中,已经进行了许多研究来评估 MS 患者治疗后基因表达的变化,特别是非编码 RNA 如 microRNAs(miRNAs)的变化。

目的

评估接受 IFN-β或 NTZ 治疗的 MS 患者中 miR-20b 表达的变化。

方法

纳入 60 例复发缓解型 MS(RRMS)患者和 30 名健康对照者(HCs)。患者分为未治疗组(N=20)、IFN-β 治疗组(N=20)和 NTZ 治疗组(N=20)。采用实时 PCR 法对全血进行表达分析。应用生物信息学工具对 miR-20b 靶基因的信号通路进行富集分析。

结果

与 HCs 相比,未经治疗的患者 miR-20b 的相对表达显著下调(-1.726 倍,p<0.001),而 IFN-β 治疗组和 NTZ 治疗组与 HCs 相比无统计学差异(IFN-β 为 0.733 倍,p=0.99;NTZ 为 1.025 倍,p=0.18)。这表明治疗患者的 miR-20b 表达恢复到正常水平。此外,计算机分析表明 Jak-STAT 信号通路富含 miR-20b 靶标(p<0.0001)。

结论

我们的研究结果表明,IFN-β 和 NTZ 在 RRMS 患者中的积极作用可能是通过使 miR-20b 表达恢复到基线来介导的。

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