Work

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

Year: 2025

Type: article

Abstract: 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. • THAP7-AS1 interacts with EIF3A in HUVECs. • THAP7-AS1 promotes EIF3A-mediated expression of ITPR1. • Increased expression of THAP7-AS1/EIF3A/ITPR1 in OGD-treated HUVECs. • Knockdown of THAP7-AS1 alleviates OGD-induced endothelial cell pyroptosis. • Overexpression of ITPR1 weakens the protective effect of TAS1-kd or EIF3A-kd on HUVECs. • Targeting ITPR1 alleviates neurological damage in ischemic stroke mice.

Source: Brain Research Bulletin

DOI: 10.1016/j.brainresbull.2025.111706

Authors: Yini Pan, Hui Chen, Jianhua Xu, Li Zhao, Meifen Yao

Institutions: Jiading District Central Hospital, Shanghai University of Medicine and Health Sciences

Language: English

Topic: Cancer-related molecular mechanisms research

Subfield: Cancer Research

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,280