RT journal article
T1 miR-16-5p Suppression Protects Human Cardiomyocytes against Endoplasmic Reticulum and Oxidative Stress-Induced Injury
A1 Toro Cebada, Rocío
A1 Perez-Serra, Alexandra
A1 Mangas Rojas, Alipio
A1 Campuzano, Oscar
A1 Sarquella-Brugada, Georgia
A1 Quezada‑Feijoo, Maribel
A1 Ramos, Mónica
A1 Alcalá, Martin
A1 Carrera, Esther
A1 García-Padilla, Carlos
A1 Franco, Diego
A1 Bonet Martínez, Fernando
A2 Medicina
K1 miR-16-5p
K1 ischemic dilated cardiomyopathy
K1 reactive oxygen species
K1 endoplasmic reticulum stress
K1 ATF6
AB Oxidative stress, defined as the excess production of reactive oxygen species (ROS) relativeto antioxidant defense, plays a significant role in the development of cardiovascular diseases. Endoplasmicreticulum (ER) stress has emerged as an important source of ROS and its modulation could becardioprotective. Previously, we demonstrated that miR-16-5p is enriched in the plasma of ischemicdilated cardiomyopathy (ICM) patients and promotes ER stress-induced apoptosis in cardiomyocytesin vitro. Here, we hypothesize that miR-16-5p might contribute to oxidative stress through ER stressinduction and that targeting miR-16-5p may exert a cardioprotective role in ER stress-mediatedcardiac injury. Analysis of oxidative markers in the plasma of ICM patients demonstrates that oxidativestress is associated with ICM. Moreover, we confirm that miR-16-5p overexpression promotesoxidative stress in AC16 cardiomyoblasts. We also find that, in response to tunicamycin-induced ERstress, miR-16-5p suppression decreases apoptosis, inflammation and cardiac damage via activatingthe ATF6-mediated cytoprotective pathway. Finally, ATF6 is identified as a direct target gene ofmiR-16-5p by dual-luciferase reporter assays. Our results indicate that miR-16-5p promotes ERstress and oxidative stress in cardiac cells through regulating ATF6, suggesting that the inhibitionof miR-16-5p has potential as a therapeutic approach to protect the heart against ER and oxidativestress-induced injury.
PB MDPI
SN 1422-0067
YR 2022
FD 2022-02
LK http://hdl.handle.net/10498/26548
UL http://hdl.handle.net/10498/26548
LA eng
DS Repositorio Institucional de la Universidad de Cádiz
RD 07-nov-2026