{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T22:21:22Z","timestamp":1783635682937,"version":"3.55.0"},"reference-count":24,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2025,9,4]],"date-time":"2025-09-04T00:00:00Z","timestamp":1756944000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of University"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>In recent years, research has focused on biomarkers as key tools to predict clinical outcomes and guide therapeutic decisions in Multiple Sclerosis (MS). MicroRNAs (miRs)\u2014small non-coding RNA molecules that regulate gene expression at the post-transcriptional level\u2014have emerged as promising biomarkers in MS due to their accessibility in biological fluids. This study investigates the role of specific serum miRs mainly involved in immune response regulation as potential prognostic biomarkers in MS, focusing on young patients with recent diagnosis. The study had a prospective design, involving a cohort of patients followed in the Hub and Spoke MS network of Verona province. Fifty-one patients (33F) aged 18\u201340 years with recent MS diagnosis (\u22642 years; 45 relapsing-remitting, 6 primary progressive) were consecutively enrolled. At baseline, serum samples were collected for miR analysis alongside clinical-demographic and MRI data, including T2 lesion volume, normalized brain volume (NBV), gray matter volume, white matter volume (WMV) calculated at baseline and annual percentage brain volume change (PBVC) and occurrence of new T2 or gadolinium-enhancing (Gd+) lesions on follow-up scans. Candidate miRs were chosen based on their potential biological role in MS pathogenesis reported in the literature. miRs assays were done using real-time PCR and expressed as a ratio relative to a normalizer (i.e., miR-425-5p). Levels of miR-34a-5p were significantly higher in patients with Gd+ lesions (p &lt; 0.001) and correlated to lower NBV (rho = \u22120.454, p = 0.001) and WMV (rho = \u22120.494, p &lt; 0.001). Conversely, miR-140-5p exhibited a protective effect against occurrence of new T2 or Gd+ lesions over time (HR 0.43; IC 95% 0.19\u20130.99; p = 0.048). Additionally, miR-30b-5p correlated directly with PBVC (adjusted rho = \u22120.646; p &lt; 0.001). These findings support the potential of serum miR-34a-5p, miR-140-5p, and miR-30b-5p as markers of disease activity and progression in patients with recently diagnosed MS.<\/jats:p>","DOI":"10.3390\/ijms26178597","type":"journal-article","created":{"date-parts":[[2025,9,4]],"date-time":"2025-09-04T10:55:37Z","timestamp":1756983337000},"page":"8597","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Serum Levels of miR-34a-5p, miR-30b-5p, and miR-140-5p Are Associated with Disease Activity and Brain Atrophy in Early Multiple Sclerosis"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3375-4098","authenticated-orcid":false,"given":"Riccardo","family":"Orlandi","sequence":"first","affiliation":[{"name":"Department of Neurological Sciences, Biomedicine and Movement Sciences, University of Verona, Piazzale Ludovico Antonio Scuro 9, 37134 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leopoldo","family":"Torresan","sequence":"additional","affiliation":[{"name":"Department of Neurological Sciences, Biomedicine and Movement Sciences, University of Verona, Piazzale Ludovico Antonio Scuro 9, 37134 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Gobbin","sequence":"additional","affiliation":[{"name":"Department of Neurological Sciences, Biomedicine and Movement Sciences, University of Verona, Piazzale Ludovico Antonio Scuro 9, 37134 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1484-4170","authenticated-orcid":false,"given":"Elisa","family":"Orlandi","sequence":"additional","affiliation":[{"name":"Department of Neurological Sciences, Biomedicine and Movement Sciences, University of Verona, Piazzale Ludovico Antonio Scuro 9, 37134 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4119-2267","authenticated-orcid":false,"given":"Macarena","family":"Gomez Lira","sequence":"additional","affiliation":[{"name":"Department of Neurological Sciences, Biomedicine and Movement Sciences, University of Verona, Piazzale Ludovico Antonio Scuro 9, 37134 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6539-0458","authenticated-orcid":false,"given":"Alberto","family":"Gajofatto","sequence":"additional","affiliation":[{"name":"Department of Neurological Sciences, Biomedicine and Movement Sciences, University of Verona, Piazzale Ludovico Antonio Scuro 9, 37134 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/S0140-6736(23)01473-3","article-title":"Multiple sclerosis","volume":"403","author":"Jakimovski","year":"2023","journal-title":"Lancet"},{"key":"ref_2","first-page":"101009","article-title":"Fluid biomarkers in multiple sclerosis: From current to future applications","volume":"44","author":"Gaetani","year":"2024","journal-title":"Lancet Reg. Health-Eur."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1155\/2013\/484959","article-title":"Clinical, MRI, and CSF markers of disability progression in multiple sclerosis","volume":"35","author":"Gajofatto","year":"2013","journal-title":"Dis. Markers"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1177\/1352458515578771","article-title":"MiRNA in multiple sclerosis: Search for novel biomarkers","volume":"21","author":"Gandhi","year":"2015","journal-title":"Mult. Scler."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Cipriano, G.L., Schepici, G., Mazzon, E., and Anchesi, I. (2024). Multiple Sclerosis: Roles of miRNA, lcnRNA, and circRNA and Their Implications in Cellular Pathways. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25042255"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e920331","DOI":"10.12659\/MSM.920331","article-title":"miR-325-3p Overexpression Inhibits Proliferation and Metastasis of Bladder Cancer Cells by Regulating MT3","volume":"26","author":"Sun","year":"2020","journal-title":"Med. Sci. Monit."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"7380","DOI":"10.1007\/s12035-019-1615-1","article-title":"Panoramic Visualization of Circulating MicroRNAs Across Neurodegenerative Diseases in Humans","volume":"56","author":"Brennan","year":"2019","journal-title":"Mol. Neurobiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1938","DOI":"10.1177\/1352458513485654","article-title":"Decreased circulating miRNA levels in patients with primary progressive multiple sclerosis","volume":"19","author":"Fenoglio","year":"2013","journal-title":"Mult. Scler."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Keller, A., Leidinger, P., Lange, J., Borries, A., Schroers, H., Scheffler, M., Lenhof, H.-P., Ruprecht, K., and Meese, E. (2009). Multiple sclerosis: microRNA expression profiles accurately differentiate patients with relapsing-remitting disease from healthy controls. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0007440"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e491","DOI":"10.1212\/NXI.0000000000000491","article-title":"Identification of MS-specific serum miRNAs in an international multicenter study","volume":"5","author":"Regev","year":"2018","journal-title":"Neurol. Neuroimmunol. Neuroinflamm."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e673","DOI":"10.1212\/NXI.0000000000000673","article-title":"CSF microRNAs discriminate MS activity and share similarity to other neuroinflammatory disorders","volume":"7","author":"Perdaens","year":"2020","journal-title":"Neurol. Neuroimmunol. Neuroinflamm."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1007\/s12017-023-08744-3","article-title":"Multiplex Analysis of Cerebrospinal Fluid and Serum Exosomes MicroRNAs of Untreated Relapsing Remitting Multiple Sclerosis (RRMS) and Proposing Noninvasive Diagnostic Biomarkers","volume":"25","author":"Mohammadinasr","year":"2023","journal-title":"Neuromol. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3342","DOI":"10.1093\/brain\/awp300","article-title":"MicroRNA profiling of multiple sclerosis lesions identifies modulators of the regulatory protein CD47","volume":"132","author":"Junker","year":"2009","journal-title":"Brain"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e267","DOI":"10.1212\/NXI.0000000000000267","article-title":"Comprehensive evaluation of serum microRNAs as biomarkers in multiple sclerosis","volume":"3","author":"Regev","year":"2016","journal-title":"Neurol. Neuroimmunol. NeuroInflamm."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1111\/ane.12921","article-title":"Evaluation of serum miR-191-5p, miR-24-3p, miR-128-3p, and miR-376c-3 in multiple sclerosis patients","volume":"138","author":"Vistbakka","year":"2018","journal-title":"Acta Neurol. Scand."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1111\/ane.13288","article-title":"Upregulated serum miR-128-3p in progressive and relapse-free multiple sclerosis patients","volume":"142","author":"Zanoni","year":"2020","journal-title":"Acta Neurol. Scand."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Agostini, S., Mancuso, R., Citterio, L.A., Caputo, D., Oreni, L., Nuzzi, R., Pasanisi, M.B., Rovaris, M., and Clerici, M. (2024). Serum miR-34a-5p, miR-103a-3p, and miR-376a-3p as possible biomarkers of conversion from relapsing-remitting to secondary progressive multiple sclerosis. Neurobiol. Dis., 200.","DOI":"10.1016\/j.nbd.2024.106648"},{"key":"ref_18","first-page":"416","article-title":"Comparison of Expression Levels of miR-29b-3p and miR-326 in T Helper-1 and T Helper-17 Cells Isolated from Responsive and Non-responsive Relapsing-remitting Multiple Sclerosis Patients Treated with Interferon-beta","volume":"19","author":"Karimi","year":"2020","journal-title":"Iran. J. Allergy Asthma Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.gene.2018.03.035","article-title":"Analysis of the expression of mir-34a, mir-199a, mir-30c and mir-19a in peripheral blood CD4+T lymphocytes of relapsing-remitting multiple sclerosis patients","volume":"659","author":"Ghadiri","year":"2018","journal-title":"Gene"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1111\/imm.12583","article-title":"Inverse correlation of expression of microRNA-140-5p with progression of multiple sclerosis and differentiation of encephalitogenic T helper type 1 cells","volume":"147","author":"Guan","year":"2016","journal-title":"Immunology"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Ebrahimkhani, S., Vafaee, F., Young, P.E., Hur, S.S.J., Hawke, S., Devenney, E., Beadnall, H., Barnett, M.H., Suter, C.M., and Buckland, M.E. (2017). Exosomal microRNA signatures in multiple sclerosis reflect disease status. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-14301-3"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Fissolo, N., Calvo-Barreiro, L., Eixarch, H., Boschert, U., Villar, L.M., Costa-Frossard, L., Ferrer, M., Sanchez, A., Borr\u00e0s, E., and Sabid\u00f3, E. (2023). Molecular signature associated with cladribine treatment in patients with multiple sclerosis. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1233546"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e030469","DOI":"10.1136\/bmjopen-2019-030469","article-title":"Biopsychosocial model of resilience in young adults with multiple sclerosis (BPS-ARMS): An observational study protocol exploring psychological reactions early after diagnosis","volume":"9","author":"Gajofatto","year":"2019","journal-title":"BMJ Open"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2\u2212\u0394\u0394CT Method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/17\/8597\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:39:16Z","timestamp":1760035156000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/17\/8597"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,4]]},"references-count":24,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2025,9]]}},"alternative-id":["ijms26178597"],"URL":"https:\/\/doi.org\/10.3390\/ijms26178597","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,4]]}}}