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.

目前尚不清楚 microRNA-133a-3p (miR-133a-3p) 在颅内动脉瘤 (IA) 中的功能作用。因此，本研究的目的是探讨 miR-133a-3p 通过磷酸丝氨酸转氨酶 1 (PSAT1)/糖原合酶激酶 3β (GSK3β)/β-连环蛋白信号传导对血管内皮损伤诱导的 IA 的调节作用途径。正常颅内小动脉组织和IA组织取自脑外伤和IA患者。通过 RT-qPCR 和蛋白质印迹分析测定组织中 miR-133a-3p、PSAT1、GSK3β 和 β-catenin 的表达。培养人 IA 的内皮细胞 (EC)，并用 miR-133a-3p 模拟物和 si-PSAT1 处理，以确定它们在内皮细胞迁移、凋亡和增殖中的功能。miR-133a-3p、PSAT1、GSK3β、β-连环蛋白、Ki-67、通过 RT-qPCR 或蛋白质印迹分析检测 EC 中的 CyclinD1、Bax 和 Bcl-2。建立IA大鼠模型,检测体内IA组织的病理变化及miR-133a-3p、PSAT1、GSK3β、β-catenin、VEGF、MMP-9的表达。miR-133a-3p的表达与IA的数量和大小有关。IA 中 MiR-133a-3p 表达下降，PSAT1、GSK3β 和 β-catenin 表达升高。恢复 miR-133a-3p 和耗尽 PSAT1 可减轻病理变化；IA 中 PSAT1、GSK3β 和 β-catenin 表达降低；抑制 IA EC 的凋亡、促进 IA EC 的增殖和迁移，并降低 IA 组织中 VEGF 和 MMP-9 的表达。我们的研究表明，IA 中 miR-133a-3p 的过表达或 PSAT1 的下调可通过抑制 GSK3β/β-catenin 通路来抑制内皮细胞损伤并促进内皮细胞增殖。MiR-133a-3p 可能是 IA 的潜在候选标记物和治疗靶点。