Abstract：
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.
To assess the changes in the expression of miR-20b in MS patients treated with IFN-β or NTZ.
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.
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).
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.
To assess the changes in the expression of miR-20b in MS patients treated with IFN-β or NTZ.
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.
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).
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：
■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了解。在过去的几十年里，已经进行了许多研究来评估MS患者治疗后的基因表达变化,特别是调节性非编码RNA,如microRNA(miRNA).
■评估用IFN-β或NTZ治疗的MS患者中miR-20b表达的变化。
■纳入60例复发缓解型MS（RRMS）患者和30例健康对照（HC）患者。患者被归类为未经治疗（N=20），IFN-β处理（N=20），和NTZ处理(N=20)。对于表达式分析，对全血进行实时PCR。生物信息学工具用于miR-20b靶组的信号通路富集分析。
■与HC相比，未经治疗的患者中miR-20b的相对表达显着下调（-1.726倍，p<0.001)，而IFN-β治疗和NTZ治疗的患者与HC相比没有统计学差异（0.733倍，IFN-β的p=0.99，为1.025倍，对于NTZ，p=0.18)。这表明在治疗的患者中miR-20b表达恢复至正常水平。此外,计算机模拟分析表明Jak-STAT信号通路富含miR-20b靶标(p<0.0001)。
■我们的发现表明，IFN-β和NTZ在RRMS患者中的积极作用可能是通过将miR-20b表达恢复到基线来介导的。
■评估用IFN-β或NTZ治疗的MS患者中miR-20b表达的变化。
■纳入60例复发缓解型MS（RRMS）患者和30例健康对照（HC）患者。患者被归类为未经治疗（N=20），IFN-β处理（N=20），和NTZ处理(N=20)。对于表达式分析，对全血进行实时PCR。生物信息学工具用于miR-20b靶组的信号通路富集分析。
■与HC相比，未经治疗的患者中miR-20b的相对表达显着下调（-1.726倍，p<0.001)，而IFN-β治疗和NTZ治疗的患者与HC相比没有统计学差异（0.733倍，IFN-β的p=0.99，为1.025倍，对于NTZ，p=0.18)。这表明在治疗的患者中miR-20b表达恢复至正常水平。此外,计算机模拟分析表明Jak-STAT信号通路富含miR-20b靶标(p<0.0001)。
■我们的发现表明，IFN-β和NTZ在RRMS患者中的积极作用可能是通过将miR-20b表达恢复到基线来介导的。
