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Circulating miR-134 in mesial temporal lobe epilepsy: implications in hippocampal sclerosis development and drug resistance

2024-12-18Research article Open access
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datacite.subject.fosCiências Médicas::Medicina Básica
dc.contributor.authorGuerra Leal, Bárbara
dc.contributor.authorCarvalho, Cláudia
dc.contributor.authorSantos, Cristina
dc.contributor.authorSamões, Raquel
dc.contributor.authorMartins-Ferreira, Ricardo
dc.contributor.authorTeixeira, Catarina
dc.contributor.authorRodrigues, Diana
dc.contributor.authorFreitas, Joel
dc.contributor.authorLemos, Carolina
dc.contributor.authorChorão, Rui
dc.contributor.authorRamalheira, João
dc.contributor.authorLopes, João
dc.contributor.authorMartins da Silva, António
dc.contributor.authorPinho E Costa, Paulo
dc.contributor.authorChaves, João
dc.date.accessioned2025-04-02T15:27:49Z
dc.date.available2025-04-02T15:27:49Z
dc.date.issued2024-12-18
dc.description(The RNA World: Non-Coding RNAs and Innovative Therapies in Neurological Disorders - Volume II)
dc.description.abstractAim: miR-134 has been widely reported as upregulated in experimental and human studies of Mesial Temporal Lobe Epilepsy the most common drug-resistant epilepsy (DRE). Studies have shown that the use of antagomirs, anti-miR-134, may be a promising therapeutic approach to these epilepsies. However, data on miR-134 in other epileptic syndromes is scarce. In this study, we aimed to quantify serum levels of miR-134 in a cohort of patients with Mesial Temporal Lobe Epilepsy-Hippocampal Sclerosis (MTLE-HS) and with Genetic Generalized Epilepsies (GGE). Additionally, we explored the correlation between miR-134 serum levels and clinical parameters, such as age at onset or febrile seizures antecedents, to evaluate its potential as a biomarker and therapeutic target in epilepsy. Methods: miR-134 levels were evaluated in cell-free serum of 131 patients with epilepsy (75 women, 56 men; age 41.10 ± 13.12 years; 72 with DRE) and 42 healthy individuals (25 women, 17 men; age 42.40 ± 9.80 years). The epilepsy cohort included 77 MTLE-HS patients and 54 GGE patients. Results: Patients with elevated miR-134 circulating levels were at higher risk of drug-resistant epilepsy (OR [95% CI] = 2.246 [1.111–4.539], p = 0.021). Other risk factors included an older age (OR [95% CI] = 1.032 [1.004–1.061], p = 0.025), history of febrile seizures (OR [95% CI] = 2.994 [1.385–6.471], p = 0.005) and higher disease duration (OR [95% CI] = 1.038 [1.011–1.066], p = 0.006). The strongest predictor of DRE was hippocampal sclerosis (OR [95% CI] = 10.338 [4.566–23.404], p < 0.001). Circulating miR-134 levels were significantly higher in MTLE-HS patients compared to controls (p < 0.05) and GGE patients (p < 0.05). However, the clinical utility of miR-134 in discriminating MTLE-HS patients from controls was only moderated (AUC = 0.651 ± 0.051 95% CI 0.551–0.751, p = 0.007). Conclusion: We show that miR-134 circulating levels are associated with DRE, especially in MTLE-HS, a syndrome characterized by severe hippocampal damage, consistent with activity-regulated miR-134 expression. This overexpression likely contributes to disease progression and our results support the potential of targeting miR-134 as a novel therapeutic approach for refractory epilepsy.eng
dc.description.sponsorshipThis study was partially funded by a BICE Tecnifar grant. Unit for Multidisciplinary Research in Biomedicine (UMIB) is funded by FCT Portugal (grant numbers UIDB/00215/2020, and UIDP/00215/2020), and the Laboratory for Integrative and Translational Research in Population Health (ITR) (LA/P/0064/2020).
dc.identifier.citationFront Mol Neurosci. 2024 Dec 18:17:1512860. doi: 10.3389/fnmol.2024.1512860. eCollection 2024
dc.identifier.doi10.3389/fnmol.2024.1512860
dc.identifier.issn1662-5099
dc.identifier.pmid39744540
dc.identifier.urihttp://hdl.handle.net/10400.18/10470
dc.language.isoeng
dc.peerreviewedyes
dc.publisherFrontiers Media
dc.relationUnit for Multidisciplinary Research in Biomedicine
dc.relationUIDP/00215/2020
dc.relationLA/P/0064/2020
dc.relation.hasversionhttps://www.frontiersin.org/journals/molecular-neuroscience/articles/10.3389/fnmol.2024.1512860
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectGGE
dc.subjectMTLE
dc.subjectBiomarkers
dc.subjectmiR-134
dc.subjectMicroRNAs
dc.subjectDoenças Genéticas
dc.titleCirculating miR-134 in mesial temporal lobe epilepsy: implications in hippocampal sclerosis development and drug resistancepor
dc.typeresearch article
dspace.entity.typePublication
oaire.awardTitleUnit for Multidisciplinary Research in Biomedicine
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F00215%2F2020/PT
oaire.citation.startPage1512860
oaire.citation.titleFrontiers in Molecular Neuroscience
oaire.citation.volume17
oaire.fundingStream6817 - DCRRNI ID
oaire.versionhttp://purl.org/coar/version/c_970fb48d4fbd8a85
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
relation.isProjectOfPublication5e782b2f-511f-446a-9c30-de1ea4f326df
relation.isProjectOfPublication.latestForDiscovery5e782b2f-511f-446a-9c30-de1ea4f326df

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