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. C...

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Main Authors: 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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Language:English
Published: KeAi Communications Co., Ltd. 2025-08-01
Series:Non-coding RNA Research
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Online Access:http://www.sciencedirect.com/science/article/pii/S2468054025000575
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author Bruna De Felice
Elisabetta Signoriello
Concetta Montanino
Giuseppe Romano
Deborah Archetto
Elisabetta Maida
Martina Marciano
Simona Bonavita
Giacomo Lus
Federica Farinella
Cinzia Coppola
author_facet Bruna De Felice
Elisabetta Signoriello
Concetta Montanino
Giuseppe Romano
Deborah Archetto
Elisabetta Maida
Martina Marciano
Simona Bonavita
Giacomo Lus
Federica Farinella
Cinzia Coppola
author_sort Bruna De Felice
collection DOAJ
description 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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spelling doaj-art-0bcfab3b038b4b9b910cd9c9b835e13a2025-08-02T04:47:31ZengKeAi Communications Co., Ltd.Non-coding RNA Research2468-05402025-08-0113174183Role of Ocrelizumab in modulating gene and microRNA expression in multiple sclerosisBruna De Felice0Elisabetta Signoriello1Concetta Montanino2Giuseppe Romano3Deborah Archetto4Elisabetta Maida5Martina Marciano6Simona Bonavita7Giacomo Lus8Federica Farinella9Cinzia Coppola10Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania “Luigi Vanvitelli”, Via Vivaldi 43, 81100, Caserta, Italy; Corresponding author.Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, Via Vivaldi 43, 81100, Caserta, ItalyDepartment of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania “Luigi Vanvitelli”, Via Vivaldi 43, 81100, Caserta, ItalyDepartment of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, Via Vivaldi 43, 81100, Caserta, ItalyDepartment of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, Via Vivaldi 43, 81100, Caserta, ItalyDepartment of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, Via Vivaldi 43, 81100, Caserta, ItalyDepartment of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, Via Vivaldi 43, 81100, Caserta, ItalyDepartment of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, Via Vivaldi 43, 81100, Caserta, ItalyDepartment of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, Via Vivaldi 43, 81100, Caserta, ItalyDepartment of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania “Luigi Vanvitelli”, Via Vivaldi 43, 81100, Caserta, ItalyDepartment of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, Via Vivaldi 43, 81100, Caserta, ItalyMultiple 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.http://www.sciencedirect.com/science/article/pii/S2468054025000575Multiple sclerosisOcrelizumabmiRNAsInteraction networkPathway analysisInflammation
spellingShingle Bruna De Felice
Elisabetta Signoriello
Concetta Montanino
Giuseppe Romano
Deborah Archetto
Elisabetta Maida
Martina Marciano
Simona Bonavita
Giacomo Lus
Federica Farinella
Cinzia Coppola
Role of Ocrelizumab in modulating gene and microRNA expression in multiple sclerosis
Non-coding RNA Research
Multiple sclerosis
Ocrelizumab
miRNAs
Interaction network
Pathway analysis
Inflammation
title Role of Ocrelizumab in modulating gene and microRNA expression in multiple sclerosis
title_full Role of Ocrelizumab in modulating gene and microRNA expression in multiple sclerosis
title_fullStr Role of Ocrelizumab in modulating gene and microRNA expression in multiple sclerosis
title_full_unstemmed Role of Ocrelizumab in modulating gene and microRNA expression in multiple sclerosis
title_short Role of Ocrelizumab in modulating gene and microRNA expression in multiple sclerosis
title_sort role of ocrelizumab in modulating gene and microrna expression in multiple sclerosis
topic Multiple sclerosis
Ocrelizumab
miRNAs
Interaction network
Pathway analysis
Inflammation
url http://www.sciencedirect.com/science/article/pii/S2468054025000575
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