Circ-GTF2I/miR-590-5p Axis Aggravates Myocardial Ischemia-Reperfusion Injury by Regulating Kelch Repeat and BTB Domain-Containing Protein 7

PURPOSE: We investigated the effect of the circular RNA (circRNA) general transcription factor IIi (GTF2I) on myocardial ischemia (MI) deterioration and neonatal rat cardiomyocyte damage. METHODS: The cell experiment was performed by using neonatal rat cardiomyocytes. Moreover, a hypoxia/reoxygenation treatment model was established. Cell Counting Kit-8 assay was conducted, and EdU cell proliferation was detected. Cell apoptosis was detected via flow cytometry and quantitative RT-PCR (RT-qPCR). Binding detection was performed through a double-luciferase reporter assay. Interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and lactate dehydrogenase (LDH) were detected via enzyme-linked immunosorbent assay (ELISA). RESULTS: Compared with that in the sham and control groups, circ-GTF2I expression in MIRI and the hypoxia/reoxygenation treatment model was significantly upregulated in vivo and in vitro. The knockdown of circ-GTF2I relieved neonatal rat cardiomyocyte damage and MI. Further detection through the double-luciferase reporter assay confirmed that the binding site of circ-GTF2I to miR-590-5p and miR-590-5p was Kelch repeat and BTB domain-containing protein 7 (KBTBD7). ELISA and RT-qPCR results showed that circ-GTF2I induced the abnormal expressions of IL-6 TNF-α, LDH, Bax, Bcl-2, and Cyt-c in MIRI and the hypoxia/reoxygenation treatment models by regulating miR-590-5p and the heart development transcription factor KBTBD7. CONCLUSIONS: CircRNA circ-GTF2I aggravated MIRI and neonatal rat cardiomyocyte damage in vivo and in vitro by regulating miR-590-5p and the heart development transcription factor KBTBD7.