Gender-dependent deregulation of linear and circular RNA variants of homer1 in the entorhinal cortex of Alzheimer’s disease

The HOMER1 gene is involved in synaptic plasticity, learning and memory. Recent studies show that circular RNA derived from HOMER1 (circHOMER1) expression is altered in some Alzheimer’s disease (AD) brain regions. In addition, HOMER1 messenger (mRNA) levels have been associated with β-Amyloid (Aβ) d...

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Detalles Bibliográficos
Autores: Urdánoz Casado, Amaya, Sánchez Ruiz de Gordoa, Javier, Robles Solano, Maitane, Acha Santamaría, Blanca, Roldán, Miren, Zelaya Huerta, María Victoria, Blanco Luquin, Idoia, Mendióroz Iriarte, Maite
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Institución:Universidad Pública de Navarra
Repositorio:Academica-e. Repositorio Institucional de la Universidad Pública de Navarra
OAI Identifier:oai:academica-e.unavarra.es:2454/41747
Acceso en línea:https://hdl.handle.net/2454/41747
Access Level:acceso abierto
Palabra clave:Alzheimer&apos
s disease
Entorhinal cortex
HOMER1
Sleep deprivation
circRNA
mRNA
Calcium
Synapses
Amyloid beta
Gender
Female
Descripción
Sumario:The HOMER1 gene is involved in synaptic plasticity, learning and memory. Recent studies show that circular RNA derived from HOMER1 (circHOMER1) expression is altered in some Alzheimer’s disease (AD) brain regions. In addition, HOMER1 messenger (mRNA) levels have been associated with β-Amyloid (Aβ) deposits in brain cortical regions. Our aim was to measure the expression levels of HOMER1 circRNAs and their linear forms in the human AD entorhinal cortex. First, we showed downregulation of HOMER1B/C and HOMER1A mRNA and hsa_circ_0006916 and hsa_circ_0073127 levels in AD female cases compared to controls by RT-qPCR. A positive correlation was observed between HOMER1B/C, HOMER1A mRNA, and hsa_circ_0073128 with HOMER1B/C protein only in females. Global average area of Aβ deposits in entorhinal cortex samples was negatively correlated with HOMER1B/C, HOMER1A mRNA, and hsa_circ_0073127 in both genders. Furthermore, no differences in DNA methylation were found in two regions of HOMER1 promoter between AD cases and controls. To sum up, we demonstrate that linear and circular RNA variants of HOMER1 are downregulated in the entorhinal cortex of female patients with AD. These results add to the notion that HOMER1 and its circular forms could be playing a female-specific role in the pathogenesis of AD.