Long non-coding RNA THAP7-AS1 interacts with EIF3A and enhances ITPR1 to enhance endoplasmic reticulum stress and endothelial cell pyroptosis in ischemic stroke

THAP7-AS1 is a newly discovered long non-coding RNA (lncRNA) whose biological roles in human physiological and pathological processes remain elusive. This study explores the functional impacts of THAP7-AS1 and its interacting molecular cascades in human umbilical vein endothelial cell damage in the context of ischemic stroke. We observed that THAP7-AS1 interacted with EIF3A in human umbilical vein endothelial cells through a combination of RNA-IP, pull-down assays, and immunofluorescence staining assays. Knockdown of either THAP7-AS1 or EIF3A led to a significant reduction in ITPR1 expression, a key regulator of Ca^{2 +} signaling and pyroptosis. In ischemic stroke models induced by oxygen-glucose deprivation (OGD), THAP7-AS1 was upregulated alongside EIF3A and ITPR1, promoting endothelial cell pyroptosis and endoplasmic reticulum (ER) stress. Knockdown of THAP7-AS1 or EIF3A alleviated OGD-induced pyroptosis and ER stress, while overexpression of ITPR1 exacerbated these conditions. In vivo, inhibition of ITPR1 with Xestospongin C reduces brain infarction and pyroptosis markers in stroke mice. These results suggest that the THAP7-AS1/EIF3A/ITPR1 axis plays a crucial role in ischemic stroke, contributing to endothelial cell dysfunction through pyroptosis and ER stress. Targeting this pathway may offer therapeutic potential for stroke-related endothelial injury.