Ocrelizumab在多发性硬化症中调节基因和microRNA表达的作用

IF 5.9 3区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Bruna De Felice , Elisabetta Signoriello , Concetta Montanino , Giuseppe Romano , Deborah Archetto , Elisabetta Maida , Martina Marciano , Simona Bonavita , Giacomo Lus , Federica Farinella , Cinzia Coppola
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引用次数: 0

摘要

多发性硬化症是一种自身免疫性神经退行性疾病,也是现代神经病学中最重大的挑战之一,影响着全球约280万人。作为一种多因素疾病,多发性硬化症的易感性可能是遗传和环境因素共同作用的结果。目前的治疗策略旨在预防急性发作,减缓疾病进展,减轻症状。Ocrelizumab是一种靶向CD20的单克隆抗体,通过降低疾病活动性和复发频率在临床试验中证明了疗效。鉴于该疗法最近获得批准,我们研究了Ocrelizumab是否会改变与神经炎症相关的关键mirna和基因的表达,如let-7a-5p、miR-14a-5p、miR-21a-5p、miR-338-3p、IL-1、IL-6、NEAT1、NEFL、NESTIN、SLC16A10和tnf - α,通过比较它们在Ocrelizumab治疗前后患者血液中的表达。此外,我们探索了基因和mirna之间潜在的负相关和直接或间接的相互作用,这些基因和mirna显示出显著的表达变化。最后,我们进行了途径分析,以了解该药物可能发挥的总体作用。结果显示,tnf - α、SLC16A10、NEFL和IL-6的表达显著降低,let-7a-5p的表达显著升高。let-7a-5p与这四个基因呈负相关,而基因之间呈正相关,说明let-7a-5p是一个共同的调节因子。这些发现表明,需要进一步的研究来确定该药物是否直接上调了let-7a-5p,从而下调了这四个基因,或者这些表达变化是否表明炎症的总体减少。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Role of Ocrelizumab in modulating gene and microRNA expression in multiple sclerosis
Multiple sclerosis is an autoimmune neurodegenerative disease and one of the most significant challenges in modern neurology, impacting approximately 2.8 million people globally. As a multifactorial condition, susceptibility to MS can result from a combination of genetic and environmental factors. Current treatment strategies aim to prevent acute attacks, slow disease progression, and alleviate symptoms. Ocrelizumab, a monoclonal antibody targeting CD20, has demonstrated efficacy in clinical trials by reducing both disease activity and frequency of relapses.
Given the recent approval of this treatment, we investigated whether Ocrelizumab alters the expression of key miRNAs and genes involved in neuroinflammation, such as let-7a-5p, miR-14a-5p, miR-21a-5p, miR-338-3p, IL-1, IL-6, NEAT1, NEFL, NESTIN, SLC16A10 and TNF-alpha, by comparing their expression in patients’ blood before and after one year of treatment with Ocrelizumab. Additionally, we explored potential inverse correlations and direct or indirect interactions among the genes and miRNAs that showed significant changes in expression. Lastly, we conducted a pathway analysis to understand the overall effects potentially exerted by the drug.
Results revealed a significant decrease in the expression of TNF-alpha, SLC16A10, NEFL and IL-6, and an increase in let-7a-5p expression. There was an inverse correlation between let-7a-5p and the four genes, while the genes positively correlated with each other, suggesting let-7a-5p as a common modulator. These findings indicate that further investigation is needed to determine if the drug directly upregulates let-7a-5p, thereby downregulating the four genes, or if these expression changes are an indication of an overall reduction in inflammation.
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来源期刊
Non-coding RNA Research
Non-coding RNA Research Medicine-Biochemistry (medical)
CiteScore
7.70
自引率
6.00%
发文量
39
审稿时长
49 days
期刊介绍: Non-coding RNA Research aims to publish high quality research and review articles on the mechanistic role of non-coding RNAs in all human diseases. This interdisciplinary journal will welcome research dealing with all aspects of non-coding RNAs-their biogenesis, regulation and role in disease progression. The focus of this journal will be to publish translational studies as well as well-designed basic studies with translational and clinical implications. The non-coding RNAs of particular interest will be microRNAs (miRNAs), small interfering RNAs (siRNAs), small nucleolar RNAs (snoRNAs), U-RNAs/small nuclear RNAs (snRNAs), exosomal/extracellular RNAs (exRNAs), Piwi-interacting RNAs (piRNAs) and long non-coding RNAs. Topics of interest will include, but not limited to: -Regulation of non-coding RNAs -Targets and regulatory functions of non-coding RNAs -Epigenetics and non-coding RNAs -Biological functions of non-coding RNAs -Non-coding RNAs as biomarkers -Non-coding RNA-based therapeutics -Prognostic value of non-coding RNAs -Pharmacological studies involving non-coding RNAs -Population based and epidemiological studies -Gene expression / proteomics / computational / pathway analysis-based studies on non-coding RNAs with functional validation -Novel strategies to manipulate non-coding RNAs expression and function -Clinical studies on evaluation of non-coding RNAs The journal will strive to disseminate cutting edge research, showcasing the ever-evolving importance of non-coding RNAs in modern day research and medicine.
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