Profile of TREM2-derived circRNA and mRNA variants in the entorhinal cortex of Alzheimer's disease patients

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dc.contributor.authorUrdánoz Casado, Amaya
dc.contributor.authorSánchez Ruiz de Gordoa, Javier
dc.contributor.authorRobles Solano, Maitane
dc.contributor.authorRoldán, Miren
dc.contributor.authorZelaya Huerta, María Victoria
dc.contributor.authorBlanco Luquin, Idoia
dc.contributor.authorMendióroz Iriarte, Maite
dc.contributor.departmentCiencias de la Saludes_ES
dc.contributor.departmentOsasun Zientziakeu
dc.contributor.funderGobierno de Navarra / Nafarroako Gobernuaes
dc.date.accessioned2023-01-13T12:07:42Z
dc.date.available2023-01-13T12:07:42Z
dc.date.issued2022
dc.date.updated2023-01-13T11:53:26Z
dc.description.abstractGenetic variants in TREM2, a microglia-related gene, are well-known risk factors for Alzheimer’s disease (AD). Here, we report that TREM2 originates from circular RNAs (circRNAs), a novel class of non-coding RNAs characterized by a covalent and stable closed-loop structure. First, divergent primers were designed to amplify circRNAs by RT-PCR, which were further assessed by Sanger sequencing. Then, additional primer sets were used to confirm back-splicing junctions. In addition, HMC3 cells were used to assess the microglial expression of circTREM2s. Three candidate circTREM2s were identified in control and AD human entorhinal samples. One of the circRNAs, circTREM2_1, was consistently amplified by all divergent primer sets in control and AD entorhinal cortex samples as well as in HMC3 cells. In AD cases, a moderate negative correlation (r = −0.434) was found between the global average area of Aβ deposits in the entorhinal cortex and circTREM2_1 expression level. In addition, by bioinformatics tools, a total of 16 miRNAs were predicted to join with circTREM2s. Finally, TREM2 mRNA corresponding to four isoforms was profiled by RTqPCR. TREM2 mRNA levels were found elevated in entorhinal samples of AD patients with low or intermediate ABC scores compared to controls. To sum up, a novel circRNA derived from the TREM2 gene, circTREM2_1, has been identified in the human entorhinal cortex and TREM2 mRNA expression has been detected to increase in AD compared to controls. Unraveling the molecular genetics of the TREM2 gene may help to better know the innate immune response in AD.en
dc.description.sponsorshipThis work was supported by the Spanish Government through grants from the Institute of Health Carlos III (FIS PI20/01701). In addition, AUC received two grants “Doctorados industriales 2018–2020” and “Contrato predoctoral en investigación en ciencias y tecnologías de la salud en el periodo 2019–2022”, both of them founded by the Government of Navarra, and MM received a grant Programa de intensificación- (LCF/PR/PR15/51100006) founded by Fundación Bancaria la Caixa and Fundación Caja-Navarra, and Contrato de Intensificación from the Institute of Health Carlos III (INT19/00029).en
dc.format.mimetypeapplication/pdfen
dc.identifier.citationUrdánoz-Casado, A., de Gordoa, J. S.-R., Robles, M., Roldan, M., Zelaya, M. V., Blanco-Luquin, I., & Mendioroz, M. (2022). Profile of TREM2-Derived circRNA and mRNA Variants in the Entorhinal Cortex of Alzheimer’s Disease Patients. International Journal of Molecular Sciences, 23(14), 7682. https://doi.org/10.3390/ijms23147682en
dc.identifier.doi10.3390/ijms23147682
dc.identifier.issn1661-6596
dc.identifier.urihttps://academica-e.unavarra.es/handle/2454/44579
dc.language.isoengen
dc.publisherMDPIen
dc.relation.ispartofInternational Journal of Molecular Sciences 2022, 23, 7682en
dc.relation.publisherversionhttps://doi.org/10.3390/ijms23147682en
dc.rights© 2022 by the authors. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) licenseen
dc.rights.accessRightsinfo:eu-repo/semantics/openAccess
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectAlzheimer's diseaseen
dc.subjectCircRNAsen
dc.subjectDAMen
dc.subjectEpigeneticsen
dc.subjectGene expressionen
dc.subjectMicrogliaen
dc.subjectRegulationen
dc.subjectTREM2en
dc.titleProfile of TREM2-derived circRNA and mRNA variants in the entorhinal cortex of Alzheimer's disease patientsen
dc.typeinfo:eu-repo/semantics/article
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dspace.entity.typePublication
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