Inhibition of lncRNA NEAT1 protects endothelial cells against hypoxia/reoxygenation‑induced NLRP3 inflammasome activation by targeting the miR‑204/BRCC3 axis.

Abstract

Cardiovascular ischemia/reperfusion (I/R) injury is primarily caused by oxygen recovery after prolonged hypoxia. Previous studies found that the long non coding RNA (lncRNA) nuclear enriched abundant transcript 1 (NEAT1) was involved in cardiovascular pathology, and that NOD-like receptor protein 3 (NLRP3) inflammasome activation-dependent pyroptosis played a key role in cardiovascular I/R injury. The present study aimed to explore the molecular mechanism of I/R pathogenesis in order to provide novel insights for potential future therapies. Cell viability and lactate dehydrogenase enzyme activity assays were used to detect cell injury after human umbilical vein endothelial cells (HUVECs) were subjected to hypoxia/reoxygenation (H/R). The expression of the NEAT1/microRNA (miR)-204/BRCA1/BRCA2-containing complex subunit 3 (BRCC3) axis was examined by reverse transcription-quantitative PCR, and the associations among genes were confirmed by luciferase reporter assays. Western blotting and ELISA were used to measure the level of NLRP3 inflammasome activation-dependent pyroptosis. The results demonstrated that NEAT1, BRCC3 expression and NLRP3 inflammasome activation-dependent pyroptosis were significantly increased in H/R-injured HUVECs, whereas silencing BRCC3 or NEAT1 attenuated H/R-induced injury and pyroptosis. NEAT1 positively regulated BRCC3 expression via competitively binding with miR-204. Moreover, NEAT1 overexpression counteracted miR-204 mimic-induced injury, BRCC3 expression and NLRP3 inflammasome activation-dependent pyroptosis. Taken together, these findings demonstrated that inhibition of lncRNA NEAT1 protects HUVECs against H/R-induced NLRP3 inflammasome activation by targeting the miR-204/BRCC3 axis.