LncRNA NR2F1-AS1 Inhibits Proliferation and Promotes Apoptosis of Vascular Smooth Muscle Cells via Downregulating AGTR1 to Participate in Intracranial Aneurysm

Abstract

Objective: Intracranial aneurysm (IA) is one of the most lethal cerebrovascular diseases, and vascular smooth muscle cells (VSMCs) abnormal proliferation and apoptosis are important features of IA. Microarray analysis showed that long non-coding RNA (lncRNA) NR2F1-AS1 (nuclear receptor subfamily 2 group F member 1 antisense RNA 1) was upregulated in patients with IA, while angiotensin II receptor type 1 (AGTR1) was downregulated. The purpose of this study was to investigate NR2F1-AS1 effect on regulating VSMC proliferation and apoptosis in IA. Material and Methods: NR2F1-AS1 and AGTR1 expression levels in blood samples of 30 IA patients and 30 healthy controls were determined by RT-qPCR (Reverse Transcription-Quantitative Polymerase Chain Reaction). The correlation between them was calculated by Spearman’s correlation test. Moreover, the VSMCs overexpressing NR2F1-AS1, AGTR1, NR2F1-AS1+AGTR1 were created, and their effects on cell proliferation and apoptosis in vitro were assessed by cell counting kit-8 (CCK-8), clone formation, and flow cytometry. Their effects on NF-κB (nuclear factor kappa-B) signal were further investigated using Western blotting. Results: NR2F1-AS1 expression level increased, while AGTR1 expression level decreased in patients with IA. NR2F1-AS1 overexpression inhibited the proliferation and increased the apoptosis of VSMCs by down-regulating AGTR1. This was followed by the inhibition of the phosphorylation level of IκB and p65 but the promotion of the IκBα expression. Conclusions: LncRNA NR2F1-AS1 downregulates AGTR1 and NF-κB signaling pathway, which inhibits the proliferation of VSMCs and promotes apoptosis, therefore promoting the development of IA.