CircCRIM1/microRNA-141-3p/thioredoxin-binding protein axis mediates neuronal apoptosis after cerebral ischemia-reperfusion

Numerous studies have indicated enrichment of circular RNA (circRNA) in the brain takes on a momentous role in cerebral ischemia-reperfusion (CIR) injury. A recent study discovered a novel circCRIM1, was highly expressed in the middle cerebral artery occlusion-reperfusion (MCAO/R) model. Nevertheless, its specific biological function remained unknown. The study was to explore circCRIM1 in CIR-induced neuronal apoptosis. As measured, circCRIM1 and TXNIP were up-regulated, while miR-141-3p was down-regulated in MCAO/R mouse model and OGD/R SH-SY5Y cells. Depleting circCRIM1 reduced the number of apoptotic neurons in MCAO/R rats, increased the number of Nissl bodies, prevented reactive oxygen species production and oxidative stress imbalance in brain tissues, repressed cleaved caspase-3, Bax, and Cyto C protein levels and increased Bcl-2 levels. Overexpression of circCRIM1 further repressed neuronal activity and accelerated apoptosis in OGD/R model, disrupted redox balance. Depleting circCRIM1 had the opposite effect in OGD/R model. Knocking down miR-141-3p or TXNIP weakened the effects of knocking down circCRIM1 or overexpressing circCRIM1, separately. Mechanistically, circCRIM1 exerted an active role in CIR injury via miR-141-3p to mediate TXNIP. All in all, the circCRIM1/miR-141-3p/TXNIP axis might be a latent therapeutic target for CIR injury.

Automated summary

Numerous studies have found that circular RNA (circRNA) plays an important role in cerebral ischemia-reperfusion (CIR) injury. A recent study discovered a novel circRNA, circCRIM1, which was highly expressed in a CIR model. This study aimed to investigate the role of circCRIM1 in CIR-induced neuronal apoptosis. The results showed that circCRIM1 was up-regulated, while miR-141-3p was down-regulated in the CIR model. Knocking down circCRIM1 reduced apoptosis and oxidative stress, while overexpression of circCRIM1 accelerated apoptosis and disrupted redox balance.