Circ_0124644 Serves as a ceRNA for miR-590-3p to Promote Hypoxia-Induced Cardiomyocytes Injury via Regulating SOX4

Abstract

Circular RNA (circRNA) is an important factor for regulating the progression of many cardiovascular diseases, including acute myocardial infarction (AMI). However, the role of circ_0124644 in AMI progression remains unclear. Hypoxia was used to induce cardiomyocytes injury. The expression of circ_0124644, microRNA (miR)-590-3p, and SRY-box transcription factor 4 (SOX4) mRNA was measured by qRT-PCR. Cell counting kit 8 (CCK8) assay and flow cytometry were utilized to detect cell viability, cell cycle progression, and apoptosis. The protein levels of apoptosis markers and SOX4 were determined by western blot (WB) analysis, and the levels of oxidative stress markers were assessed using commercial Assay Kits. Dual-luciferase reporter assay, RIP assay, and RNA pull-down assay were employed to confirm the interaction between miR-590-3p and circ_0124644 or SOX4. Circ_0124644 was upregulated in AMI patients and hypoxia-induced cardiomyocytes. Hypoxia could inhibit cardiomyocytes viability, cell cycle process, and promote apoptosis and oxidative stress, while silencing circ_0124644 could alleviate hypoxia-induced cardiomyocytes injury. In terms of mechanism, circ_0124644 could target miR-590-3p. MiR-590-3p overexpression could relieve hypoxia-induced cardiomyocytes injury. Also, the suppressive effect of circ_0124644 knockdown on hypoxia-induced cardiomyocytes injury could be reversed by miR-590-3p inhibitor. Moreover, SOX4 was found to be a target of miR-590-3p, and its overexpression also could reverse the regulation of miR-590-3p on hypoxia-induced cardiomyocytes injury. Circ_0124644 silencing could alleviate hypoxia-induced cardiomyocytes injury by regulating the miR-590-3p/SOX4 axis, suggesting that it might be a target for alleviating AMI.

Circ_ROBO2/miR-186-5p/TRIM14 axis regulates oxidized low-density lipoprotein-induced cardiac microvascular endothelial cell injury

“…Circ_ROBO2 has been reported to promote ox-LDL-mediated endothelial injury in human vascular endothelial cells [ 32 ]. Moreover, circ_ROBO2 promoted hypoxia-induced cardiomyocytes damage via regulation of miR-590-3p/SOX4 axis [ 33 ]. In addition, circ_ROBO2 knockdown inhibited the proliferation and migration in PDGF-BB-treated human aortic smooth muscle cells [ 34 ].…”

Emerging roles of circRNAs in the pathological process of myocardial infarction

“…Silencing of circ_0124644 attenuates hypoxia-induced cardiomyocyte injury, such as by suppressing apoptosis and oxidative stress and inhibiting AMI progression through the circ_0124644/miR-590-3p/SOX4 axis. 107 In addition, it was demonstrated that knockdown of circROBO2 alleviates hypoxia-induced cardiomyocyte injury and apoptosis and improves cardiac dysfunction by modulating the circROBO2/miR-1184/TNFR1-associated death domain protein (TRADD) axis. 108 Finally, Wu et al.…”

“…circ_0124644 was demonstrated to be a diagnostic biomarker for CAD, including MI, because it is easily detected in peripheral blood with high specificity and sensitivity and because its expression is upregulated in serum samples from AMI patients, suggesting that its diagnostic value would be greater when combined with circ_0098964. 107 , 146 Li et al. 132 proposed that the circPAN3/miR-221/Foxo3/ATG7 axis, a strong predictor of cardiac fibrosis during MI, may serve as a sensitive biomarker for cardiac fibrosis during MI.…”

“…Finally, it is worth noting that circRNA_081881, circRNA MICRA, and circ_LAS1L expression levels are decreased in the blood samples of patients with AMI and that hsa_circ_0124644 expression is upregulated in the peripheral blood of CAD patients. 107 , 135 , 142 , 145 , 146 …”

“…For example, circRNA MFACR, circ_0062389, circ-0068655, circ_0010729, circRNA ACAP2, circ_0124644, circROBO2, circMACF1, and circArhgap12 may exert potential anti-apoptotic effects to inhibit AMI progression. 33 , 94 , 100 , 101 , 104 , 105 , 107 , 108 , 111 , 116 In addition, circRNA ACR may have an effective anti-autophagic effect. 120 During infarct healing, circHelz can exert anti-inflammatory effects, 122 circCDYL and circFASTKD1 are likely to contribute to proliferation and proangiogensis, 123 , 127 and circUbe3a can exert anti-fibrotic effects.…”