miR-16-5p Suppression Protects Human Cardiomyocytes against Endoplasmic Reticulum and Oxidative Stress-Induced Injury

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2022-02Department
MedicinaSource
Int. J. Mol. Sci. 2022, 23(3), 1036Abstract
Oxidative stress, defined as the excess production of reactive oxygen species (ROS) relative
to antioxidant defense, plays a significant role in the development of cardiovascular diseases. Endoplasmic
reticulum (ER) stress has emerged as an important source of ROS and its modulation could be
cardioprotective. Previously, we demonstrated that miR-16-5p is enriched in the plasma of ischemic
dilated cardiomyopathy (ICM) patients and promotes ER stress-induced apoptosis in cardiomyocytes
in vitro. Here, we hypothesize that miR-16-5p might contribute to oxidative stress through ER stress
induction and that targeting miR-16-5p may exert a cardioprotective role in ER stress-mediated
cardiac injury. Analysis of oxidative markers in the plasma of ICM patients demonstrates that oxidative
stress is associated with ICM. Moreover, we confirm that miR-16-5p overexpression promotes
oxidative stress in AC16 cardiomyoblasts. We also find that, in response to tunicamycin-induced ER
stress, miR-16-5p suppression decreases apoptosis, inflammation and cardiac damage via activating
the ATF6-mediated cytoprotective pathway. Finally, ATF6 is identified as a direct target gene of
miR-16-5p by dual-luciferase reporter assays. Our results indicate that miR-16-5p promotes ER
stress and oxidative stress in cardiac cells through regulating ATF6, suggesting that the inhibition
of miR-16-5p has potential as a therapeutic approach to protect the heart against ER and oxidative
stress-induced injury.
Subjects
miR-16-5p; ischemic dilated cardiomyopathy; reactive oxygen species; endoplasmic reticulum stress; ATF6Collections
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