MicroRNA-124 regulates cell pyroptosis during cerebral ischemia-reperfusion injury by regulating STAT3.

ABSTRACT

Cerebral ischemia-reperfusion injury (CIRI) is the observed continuation and deterioration of ischemic injury, and currently, there are no effective treatment strategies for the condition. It has been reported that microRNAs (miRNAs) serve an important role in CIRI by regulating pyroptosis. The present study demonstrated that miRNA-124 regulated CIRI by regulating STAT3. To explore the relationship between miRNA-124/STAT3 and pyroptosis in CIRI, CIRI was simulated using a middle cerebral artery occlusion model. Subsequently, miRNA-124 expression levels were altered via the intracerebroventricular injection of miRNA-124 agonist or antagonist. The degree of brain tissue injury was assessed by conducting TTC staining and neurological function scoring. Relative miRNA-124 expression levels were determined via reverse transcription-quantitative PCR. A luciferase reporter gene system verified the targeted binding of miRNA-124 to STAT3. The expression levels of key proteins and proinflammatory cytokines associated with pyroptosis [caspase-1, gasdermin D, interleukin (IL)-18 and IL-1ß] were detected via western blotting and immunohistochemistry. The increased expression levels of pyroptosis-associated proteins and proinflammatory cytokines in the I/R groups compared with the control group, indicated that pyroptosis intensified over time during CIRI, and miRNA-124 agonist significantly abrogated pyroptosis and improved neurological function compared with the control group. Furthermore, miRNA-124 inhibited STAT3 activation in a targeted manner, which also decreased the extent of pyroptosis. However, miRNA-124 antagonist reversed miR-124 agonist-mediated effects. Therefore, the present study indicated that miRNA-124 may provide neuroprotection against pyroptosis during CIRI, potentially via inhibition of the STAT3 signaling pathway.