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-1β] 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.

MicroRNA-26b-5p alleviates cerebral ischemia-reperfusion injury in rats via inhibiting the N-myc/PTEN axis by downregulating KLF10 expression

“…3,4 This part of aberrantly expressed miRNAs are mainly involved in the regulation of the occurrence and development of CIRI by affecting life activities such as energy metabolism, apoptosis, ROS production and secretion of inflammatory cytokines IL-6 and TNF-α. 5,6 Our previous gene analysis found that the expression of miR-26b-5p was downregulated in the infarcted brain tissue of cerebral ischemia-reperfusion rats, which was consistent with the results of another gene chip analysis. 7 Recently, microarray analysis of mouse cerebral artery ischemia model showed that miR-26b-5p was downregulated in CIR brain tissue.…”

miRNA Involvement in Cerebral Ischemia-Reperfusion Injury

“…Gastrodin regulated the miR-22/NEAT1 axis and reduced the pro-inflammatory cytokines, reducing pyroptosis and attenuating the I/R injuries both in vivo and in vitro (Zhang et al, 2021a). MiR-124, which was previously discussed for apoptosis and was described as a marker of I/R injury, inhibits STAT3 expression and thereby reduces pyroptosis and improves the neurological outcome (Sun et al, 2020a). Overall, more studies are needed in order to fully elucidate how miRNAs regulation is related to pyroptosis and how these could potentially be used as therapeutic targets.…”

Pyroptosis: A Newly Discovered Therapeutic Target for Ischemia-Reperfusion Injury

“…Meanwhile, microRNAs are a class of small non-coding RNAs that play a significant role in various biological processes related to cell death. A recent study has suggested that microRNA-124 inhibits pyroptosis induced by cerebral I/R injury by regulating the STAT3 signaling pathway [ 58 ]. Furthermore, it has been suggested that ginsenoside Rd could attenuate cerebral I/R injury by exerting an anti-pyroptotic effect via the miR-139-5p/Keap1/Nrf2 axis [ 59 ].…”