Nanoscale Res Lett 2020 Sep 9;15(1):177. Epub 2020 Sep 9.
Clinical Laboratory, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, 314 An shan xin Road, Nan Kai District, Tianjin, 300000, Tianjin, China.
It is unclear about the functional role of microRNA-133a-3p (miR-133a-3p) in intracranial aneurysm (IA). Hence, the aim of the present study was to investigate the regulatory role of miR-133a-3p on the regulation of vascular endothelial injury-induced IA through phosphoserine aminotransferase 1 (PSAT1)/glycogen synthase kinase 3β (GSK3β)/β-catenin signaling pathway. Normal intracranial arteriole tissues and IA tissues were gathered from patients with brain trauma and IA. The expression of miR-133a-3p, PSAT1, GSK3β, and β-catenin in tissues was determined by RT-qPCR and western blot analysis. The endothelial cells (ECs) of the human IA were cultured and treated with miR-133a-3p mimic and si-PSAT1 to determine their functions in endothelial cell migration, apoptosis, and proliferation. The expression of miR-133a-3p, PSAT1, GSK3β, β-catenin, Ki-67, CyclinD1, Bax, and Bcl-2 in ECs were tested by RT-qPCR or western blot analysis. Moreover, IA rat model was established to detect the pathological changes and the expression of miR-133a-3p, PSAT1, GSK3β, β-catenin, VEGF, and MMP-9 in IA tissues in vivo. Expression of miR-133a-3p was related to the number and size of IA. MiR-133a-3p expression was deceased and the PSAT1, GSK3β, and β-catenin expression was raised in IA. Restored miR-133a-3p and depleted PSAT1 alleviated the pathological change; reduced PSAT1, GSK3β, and β-catenin expression in IA; suppressed apoptosis and advanced proliferation and migration of IA ECs, as well as reduced VEGF and MMP-9 expression in IA tissues in vivo. Our study suggests that overexpression of miR-133a-3p or downregulation of PSAT1 restrains endothelial cell damage and advances endothelial cell proliferation via inhibiting the GSK3β/β-catenin pathway in IA. MiR-133a-3p might be a potential candidate marker and therapeutic target for IA.