Withdrawn: MicroRNA‐142‐5p inhibits autophagy in cardiomyocytes in a mouse model of hypoxia/reoxygenation

Abstract

Cardiomyocyte hypoxia-and ischemia-induced apoptosis is a key challenge in the treatment of cardiovascular diseases, and it has been previously reported that high glucose-induced cardiomyocyte apoptosis can be prevented by autophagy activation. Furthermore, down-regulation of the microRNA miR-142-5p protects cardiomyocytes against hypoxia. However, the effects of miR-142-5p on autophagy of myocardial cells under hypoxia/reoxygenation (H/R) are less well understood. Here, we observed that the optimal time for hypoxia and re-oxygenation was 4 hours (h) and 8 h in our model. Overexpression of miR-142-5p in a cardiomyocyte model of H/R enhanced apoptosis and increased the expression of interleukin-1β (IL-1β), cleaved-caspase 3 and p62, but inhibited autophagy and decreased expression of Beclin-1, protein 1 light chain 3B (LC3B) and B cell leukemia/lymphoma 2 (Bcl-2) at the mRNA and protein level. Silencing of miR-142-5p had the opposite effects. We identified Beclin-1 as a target gene for miR-142-5p. Down-regulation of Beclin-1 inhibited autophagy, with down-regulation of LC3B and up-regulation of p62, but promoted apoptosis in the H/R model; down-regulation of miR-142-5p promoted autophagy and inhibited apoptosis in cardiomyocytes through up-regulation of BECN1. Our results provide new insights that may facilitate the development of treatments for ischemic heart disease.

Sevoflurane exerts improved protective effects than propofol on hypoxia‑reoxygenation injury by regulating the microRNA‑221‑5p/ADAM8 axis in cardiomyocytes

“…For example, a study revealed that miR-101a-3p suppressed H9C2 cell proliferation and, during H/R injury, promoted H9C2 cell apoptosis ( 18 ). Likewise, miR-142-p could promote cell apoptosis in a cardiomyocyte model of H/R injury ( 19 ). Upregulation of miR-221-5p was observed in myocardial hypertrophy and heart failure ( 20 ).…”