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

Pérez-Carrillo, Lorena; Giménez-Escamilla, Isaac; García-Manzanares, María; Triviño, Juan Carlos; Feijóo-Bandín, Sandra; Aragón-Herrera, Alana; Lago, Francisca; Martínez-Dolz, Luis; Portolés, Manuel; Tarazón, Estefanía; Roselló-Lletí, Esther

doi:10.3390/antiox12071337

Open AccessArticle

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

by

Lorena Pérez-Carrillo

^1,2,

Isaac Giménez-Escamilla

^1,2

,

María García-Manzanares

^2,3,

Juan Carlos Triviño

⁴

,

Sandra Feijóo-Bandín

^2,5

,

Alana Aragón-Herrera

^2,5

,

Francisca Lago

^2,5,

Luis Martínez-Dolz

^1,2,6

,

Manuel Portolés

^1,2

,

Estefanía Tarazón

^1,2,*,†

and

Esther Roselló-Lletí

^1,2,*,†

¹

Clinical and Translational Research in Cardiology Unit, Health Research Institute Hospital La Fe (IIS La Fe), Avd. Fernando Abril Martorell 106, 46026 Valencia, Spain

²

Center for Biomedical Research Network on Cardiovascular Diseases (CIBERCV), Avd. Monforte de Lemos 3-5, 28029 Madrid, Spain

³

Medicine and Animal Surgery, Veterinary School, CEU Cardenal Herrera University, C/Lluís Vives, 1, 46115 Alfara del Patriarca, Spain

⁴

Genomic Systems, Ronda de Guglielmo Marconi, 6, 46980 Paterna, Spain

⁵

Cellular and Molecular Cardiology Research Unit, Department of Cardiology and Institute of Biomedical Research, University Clinical Hospital, Tr.ª da Choupana, 15706 Santiago de Compostela, Spain

⁶

Heart Failure and Transplantation Unit, Cardiology Department, University and Polytechnic La Fe Hospital, Avd. Fernando Abril Martorell 106, 46026 Valencia, Spain

^*

Authors to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

Antioxidants 2023, 12(7), 1337; https://doi.org/10.3390/antiox12071337

Submission received: 27 April 2023 / Revised: 19 June 2023 / Accepted: 21 June 2023 / Published: 24 June 2023

(This article belongs to the Special Issue Role of Oxidative Stress in Cardiac Remodeling and Heart Failure—2nd Edition)

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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 ± 0.94 au vs. 5.34 ± 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.

Keywords: microRNA biogenesis; redoximiRs; ischemic cardiomyopathy; microRNA maturation

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MDPI and ACS Style

Pérez-Carrillo, L.; Giménez-Escamilla, I.; García-Manzanares, M.; Triviño, J.C.; Feijóo-Bandín, S.; Aragón-Herrera, A.; Lago, F.; Martínez-Dolz, L.; Portolés, M.; Tarazón, E.; et al. Altered MicroRNA Maturation in Ischemic Hearts: Implication of Hypoxia on XPO5 and DICER1 Dysregulation and RedoximiR State. Antioxidants 2023, 12, 1337. https://doi.org/10.3390/antiox12071337

AMA Style

Pérez-Carrillo L, Giménez-Escamilla I, García-Manzanares M, Triviño JC, Feijóo-Bandín S, Aragón-Herrera A, Lago F, Martínez-Dolz L, Portolés M, Tarazón E, et al. Altered MicroRNA Maturation in Ischemic Hearts: Implication of Hypoxia on XPO5 and DICER1 Dysregulation and RedoximiR State. Antioxidants. 2023; 12(7):1337. https://doi.org/10.3390/antiox12071337

Chicago/Turabian Style

Pérez-Carrillo, Lorena, Isaac Giménez-Escamilla, María García-Manzanares, Juan Carlos Triviño, Sandra Feijóo-Bandín, Alana Aragón-Herrera, Francisca Lago, Luis Martínez-Dolz, Manuel Portolés, Estefanía Tarazón, and et al. 2023. "Altered MicroRNA Maturation in Ischemic Hearts: Implication of Hypoxia on XPO5 and DICER1 Dysregulation and RedoximiR State" Antioxidants 12, no. 7: 1337. https://doi.org/10.3390/antiox12071337

APA Style

Pérez-Carrillo, L., Giménez-Escamilla, I., García-Manzanares, M., Triviño, J. C., Feijóo-Bandín, S., Aragón-Herrera, A., Lago, F., Martínez-Dolz, L., Portolés, M., Tarazón, E., & Roselló-Lletí, E. (2023). Altered MicroRNA Maturation in Ischemic Hearts: Implication of Hypoxia on XPO5 and DICER1 Dysregulation and RedoximiR State. Antioxidants, 12(7), 1337. https://doi.org/10.3390/antiox12071337

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

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