The circular RNA Cdr1as promotes myocardial infarction by mediating the regulation of miR-7α on Its Target Genes Expression

Abstract

Objectives: Recent studies have demonstrated the role of Cdr1as (or CiRS-7), one of the well-identified circular RNAs (circRNAs), as a miR-7α/b sponge or inhibitor in brain tissues or islet cells. This study aimed to investigate the presence of Cdr1as/miR-7α pathway in cardiomyocytes, and explore the mechanism underlying the function of miR-7α in protecting against myocardial infarction (MI)-inducedapoptosis. Methods: Mouse MI injury model was established and evaluated by infarct size determination. Realtime PCR was performed to quantify the expression of Cdr1as and miR-7α in cardiomyocytes. Cell apoptosis was determined by caspase-3 activity analysis and flow cytometry assays with Annexin V/PI staining. Transfection of Cdr1as overexpressing plasmid and miR-7α mimic were conducted for gain-of-function studies. Luciferase reporter assay and western blot analysis were performed to verity potential miR-7α targets. Results: Cdr1as and miR-7αwere both upregulated in MI mice with increased cardiac infarct size, or cardiomyocytes under hypoxia treatment. Cdr1as overexpression in MCM cells promoted cell apoptosis, but was then reversed by miR-7α overexpression. The SP1 was identified as a new miR-7α target, in line with previously identified PARP, while miR-7α-induced decrease of cell apoptosis under hypoxia treatment was proven to be inhibited by PARP-SP1 overexpression. Moreover, Cdr1as overexpression in vivo increased cardiac infarct size with upregulated expression of PARP and SP1, while miR-7α overexpression reversed these changes. Conclusions: Cdr1as also functioned as a powerful miR-7α sponge in myocardial cells, and showed regulation on the protective role of miR-7α in MI injury, involving the function of miR-7α targets, PARP and SP1.