Abstract
Introduction: Ischemic stroke, an abrupt blockage of artery, accounting for the most cases of stroke, causes high neurological mortality across the world. Recent evidence has uncovered that circular RNAs (circRNAs) highly engage in ischemic stroke-related neuronal injury. This study concentrated on a novel circRNA hsa_circ_0000304 (termed as circCELF1), trying to unveil its role and underlying mechanism in ischemic stroke. Methods: RT-qPCR and Western blot assays were conducted to detect the expression levels of RNA and protein, respectively. Functional analysis was performed to evaluate the influences of circCELF1 expression on astrocyte apoptosis and autophagy. Multiple mechanism assays were performed to probe the molecular mechanism underlying circCELF1 regulation. The oxygen-glucose deprivation/reoxygenation (OGD/R)-induced astrocytes model and transient middle cerebral artery occlusion (tMCAO) mouse model were constructed. Results: circCELF1 was found to be upregulated in OGD/R-induced astrocytes, relative to normal astrocytes. circCELF1 knockdown repressed the apoptosis and autophagy of astrocytes. The in vivo study conducted with the tMCAO model also revealed that circCELF1 or NFAT5 deficiency contributed to the suppression of neural injury. Further, circCELF1 was uncovered to elevate NFAT5 expression via recruiting DDX54, functionally promoting astrocyte apoptosis and autophagy. Conclusion: circCELF1 recruits DDX54 to upregulate NFAT5, by which astrocyte apoptosis and autophagy are stimulated.
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