PVT1 alleviates hypoxia-induced endothelial apoptosis by enhancing autophagy via the miR-15b-5p/ATG14 and miR-424-5p/ATG14 axis

Endothelial dysfunction plays a crucial role in the pathogenesis of vascular disease. Long noncoding RNA (lncRNA) and microRNA (miRNA) play important roles in various cellular processes and are involved in several vascular endothelial cells (VECs) biological processes, including cell growth, migration, auto-phagy, and apoptosis. The functions of plasmacytoma variant translocation 1 (PVT1) in VECs have been progressively investigated in recent years, mainly with regard to proliferation and migration of endo-thelial cells (ECs). However, the mechanism underlying the regulation of autophagy and apoptosis in human umbilical vein endothelial cells (HUVEC) by PVT1 remains unclear. The present study showed that PVT1 knockdown accelerated apoptosis induced by oxygen and glucose deprivation (OGD) through suppression of cellular autophagy. Bioinformatic prediction of PVT1 target miRNAs revealed that PVT1 interacts with miR-15b-5p and miR-424-5p. The study further showed that miR-15b-5p and miR-424-5p inhibit the functions of autophagy related 14 (ATG14) and suppress cellular autophagy. The results showed that PVT1 can function as a competing endogenous RNA (ceRNA) of miR-15b-5p and miR-424-5p and promote cellular autophagy by competitive binding, which down-regulates apoptosis. The results showed that PVT1 can function as a competing endogenous RNA (ceRNA) of miR-15b-5p and miR-424-5p and promote cellular autophagy through competitive binding, which down-regulates apoptosis. The study provides insight into a novel therapeutic target that may be explored in the future for the treat-ment of cardiovascular disease. & COPY; 2023 Elsevier Inc. All rights reserved.

Automated summary

Endothelial dysfunction is crucial in vascular disease pathogenesis. Long noncoding RNA (lncRNA) and microRNA (miRNA) play significant roles in various cellular processes in vascular endothelial cells (VECs), including cell growth, migration, autophagy, and apoptosis. The present study investigated the role of plasmacytoma variant translocation 1 (PVT1) in regulating autophagy and apoptosis in human umbilical vein endothelial cells (HUVEC). It was found that PVT1 knockdown accelerates apoptosis and suppresses cellular autophagy. PVT1 functions as a competing endogenous RNA (ceRNA) of miR-15b-5p and miR-424-5p, promoting cellular autophagy and down-regulating apoptosis. This study suggests PVT1 as a potential therapeutic target for cardiovascular disease treatment.