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  3. Altered MicroRNA Maturation in Ischemic Hearts: Implication of Hypoxia on XPO5 and DICER1 Dysregulation and RedoximiR State

Altered MicroRNA Maturation in Ischemic Hearts: Implication of Hypoxia on XPO5 and DICER1 Dysregulation and RedoximiR State

Fecha de publicación:

Autores de IIS La Fe

Participantes ajenos a IIS La Fe

  • García-Manzanares, M
  • Triviño, JC
  • Feijóo-Bandín, S
  • Aragón-Herrera, A
  • Lago, F

Grupos

Abstract

Ischemic cardiomyopathy (ICM) is associated with abnormal microRNA expression levels that involve an altered gene expression profile. However, little is known about the underlying causes of microRNA disruption in ICM and whether microRNA maturation is compromised. Therefore, we focused on microRNA maturation defects analysis and the implication of the microRNA biogenesis pathway and redox-sensitive microRNAs (redoximiRs). Transcriptomic changes were investigated via ncRNA-seq (ICM, n = 22; controls, n = 8) and mRNA-seq (ICM, n = 13; control, n = 10). The effect of hypoxia on the biogenesis of microRNAs was evaluated in the AC16 cell line. ICM patients showed a reduction in microRNA maturation compared to control (4.30 & PLUSMN; 0.94 au vs. 5.34 & PLUSMN; 1.07 au, p < 0.05), accompanied by a deregulation of the microRNA biogenesis pathway: a decrease in pre-microRNA export (XPO5, FC = -1.38, p < 0.05) and cytoplasmic processing (DICER, FC = -1.32, p < 0.01). Both processes were regulated by hypoxia in AC16 cells (XPO5, FC = -1.65; DICER1, FC = -1.55; p < 0.01; Exportin-5, FC = -1.81; Dicer, FC = -1.15; p < 0.05). Patients displayed deregulation of several redoximiRs, highlighting miR-122-5p (FC = -2.41, p < 0.001), which maintained a good correlation with the ejection fraction (r = 0.681, p < 0.01). We evidenced a decrease in microRNA maturation mainly linked to a decrease in XPO5-mediated pre-microRNA export and DICER1-mediated processing, together with a general effect of hypoxia through deregulation of biogenesis pathway and the redoximiRs.

Datos de la publicación

ISSN/ISSNe:
2076-3921, 2076-3921

Antioxidants  MDPI

Tipo:
Article
Páginas:
-
PubMed:
37507877
Factor de Impacto:
1,008 SCImago ℠
Cuartil:
Q1 SCImago ℠

Citas Recibidas en Web of Science: 3

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Keywords

  • microRNA biogenesis; redoximiRs; ischemic cardiomyopathy; microRNA maturation

Proyectos y Estudios Clínicos

Contratos Miguel Servet 2021. Estefanía Tarazón.

Investigador Principal: ESTEFANÍA TARAZÓN MELGUIZO

CP21/00041 . INSTITUTO DE SALUD CARLOS III . 2022

Contrato PFIS 2021. Isaac Giménez

Investigador Principal: ESTEFANÍA TARAZÓN MELGUIZO

FI21/00034 . INSTITUTO DE SALUD CARLOS III . 2022

Contrato PFIS 2021. Lorena Pérez

Investigador Principal: ESTHER ROSELLÓ LLETÍ

FI21/00186 . INSTITUTO DE SALUD CARLOS III . 2022

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