CircRNA 010567 plays a significant role in myocardial infarction via the regulation of the miRNA-141/DAPK1 axis

Myocardial infarction (MI), caused by temporary or permanent coronary artery occlusion, poses a serious threat to patients' lives. Circular RNAs (circRNAs), a new kind of endogenous noncoding RNAs, have been widely studied recently. This study was designed to illustrate and potential molecular mechanisms of circRNA 010567 in hypoxia-induced cardiomyocyte injury in vitro, so as to provide new strategies for the therapy of MI.

Our results demonstrated that circRNA 010567-siRNA played a protective role in hypoxia-induced cardiomyocyte damage via regulating the miR-141/DAPK1 axis, indicating that circRNA 010567-siRNA may be a promising target for MI therapy.

H9c2 cells were cultured in anoxic conditions with 94% N2, 5% CO2, and 1% O2 to establish the in vitro MI model. Cell viability and apoptosis were checked using MTT and flow cytometry assay, respectively, Moreover, the levels of circRNA 010567, miR-141, and DAPK1 was determined using qRT-PCR. The putative targets of circRNA 010567 and miR-141 were confirmed by dual-luciferase reporter system and the RNA immunoprecipitation (RIP) assay. The release of creatine kinase-MB (CK-MB), cardiac troponin I (cTnI), and the viability of mitochondria were detected using assay kits.

The current study revealed that circRNA 010567 and DAPK1 were over-expressed, and miR-141 was low-expressed in hypoxia-induced MI. circRNA 010567 sponges miR-141 and DAPK1 was a direct target of miR-141. Mechanistic investigations revealed that circRNA 010567-siRNA impaired the release of CK-MB and cTnI, and promoted the viability of mitochondria in hypoxia-induced H9c2 cells, while these findings were reversed by the miR-141 inhibitor. In addition, the miR-141 mimic markedly reduced the release of CK-MB and cTnI, and promoted the viability of mitochondria, and these results were reversed by the DAPK1-plasmid. Subsequently, functional experiments revealed that hypoxia-stimulated decreases in H9c2 cell viability, as well as increases in apoptosis and caspase-3 activity, were induced by the miR-141 mimic and circRNA 010567-siRNA. However, these results were reversed by the miR-141 inhibitor and DAPK1-plasmid. Conclusions: Our results demonstrated that circRNA 010567-siRNA played a protective role in hypoxia-induced cardiomyocyte damage via regulating the miR-141/DAPK1 axis, indicating that circRNA 010567-siRNA may be a promising target for MI therapy.