LncRNA PVT1 in brain injury induced by deep hypothermia and low flow

Abstract

AimsTo analyze the role of lncRNA PVT1 in cerebral ischemia-reperfusion (I/R) injury induced by deep hypothermia low flow (DHLF).Methods and resultsA total of 72 lncRNAs were differentially expressed in the brain tissue of DHLF mice. PVT1 expression was significantly downregulated in DHLF mouse brain tissue, preoperative and postoperative blood samples from children undergoing DHLF extracorporeal circulation, and hOGD-treated cells. In the mouse model, the DHLF group with PVT1 overexpression had heavier brain tissue damage than the control group; apoptosis rate, reactive oxygen species level and caspase-3 enzyme activity were significantly higher in the lenti-PVT1 group than in the lenti-control group. Compared those in the lenti-control group, the total distance traveled, distance of action in the center, number of entering the center, average speed of walking reduced, and the distance of walking in the periphery and and peripheral walking distance increased in the lenti-PVT1 group. The dual luciferase reporter gene assay verified the possible binding sites between PVT1, miR-148a-3p and MKL1. In the animal model, cellular model, and blood samples of children experiencing DHLF, miR-148a-3p expression increased and MKL1 expression decreased. In experimental studies in vivo and in vitro, PVT1 and MKL1 expression increased, and miR-148a-3p expression decreased. Meanwhile MKL1 inhibitor CCG1423 reversed the apoptosis in neuronal cells.ConclusionPVT1 may adsorb miR-148a-3p to regulate the expression of MKL1, a downstream gene of miR-148a-3p, a mechanism promoting the apoptosis of neuronal cells in DHLF mice.