Department of Neurosurgery, Centre Hospital of Weihai, Weihai, Shandong, China (mainland).
Department of Gastroenterology, Centre Hospital of Weihai, Weihai, Shandong, China (mainland).
Med Sci Monit. 2019 Feb 11;25:1133-1139. doi: 10.12659/MSM.912204.
BACKGROUND Preliminary microarray data in our laboratory indicated that the novel long noncoding RNA (lncRNA), GASL1, was downregulated in patients with intracranial aneurysms. This study aimed to investigate the expression of lncRNA GASL1 in patients with intracranial aneurysms and its role in the regulation of vascular smooth muscle cell (VSMC) proliferation by transforming growth factor-β1 (TGF-β1). MATERIAL AND METHODS The study included 68 patients with unruptured intracranial aneurysms and 56 healthy volunteers. In both groups, serum levels of TGF-β1 were measured using an enzyme-linked immunoassay (ELISA) and Western blot. Human VSMCs in vitro underwent lncRNA GASL1 overexpression using the insertion of an EcoRI-EcoRI fragment into the pIRSE2 vector. Cell viability and proliferation were measured by a cell counting kit-8 (CCK-8) assay. RNA extraction and quantitative real-time polymerase chain reaction (qRT-PCR) determined GASL1 expression. RESULTS ROC curve analysis showed that downregulation of GASL1 effectively distinguished patients with intracranial aneurysm from healthy controls. Blood GASL1 and TGF-β1 were negatively correlated in patients with intracranial aneurysm but not in healthy people. GASL1 overexpression promoted proliferation of human vascular smooth muscle cells (VSMCs) and downregulated TGF-β1 expression, while exogenous TGF-β1 reduced VSMCs proliferation but showed no effects on GASL1 expression. CONCLUSIONS Expression of the novel lncRNA, GASL1, was downregulated in patients with intracranial aneurysms and regulated the proliferation of VSMCs in vitro by targeting TGF-β1.
我们实验室的初步基因芯片数据表明,新型长链非编码 RNA(lncRNA)GASL1 在颅内动脉瘤患者中下调。本研究旨在探讨 lncRNA GASL1 在颅内动脉瘤患者中的表达及其在转化生长因子-β1(TGF-β1)调节血管平滑肌细胞(VSMC)增殖中的作用。
该研究纳入了 68 例未破裂颅内动脉瘤患者和 56 名健康志愿者。在两组中,均采用酶联免疫吸附试验(ELISA)和 Western blot 法检测 TGF-β1 血清水平。体外通过将 EcoRI-EcoRI 片段插入 pIRSE2 载体来实现 lncRNA GASL1 的过表达。通过细胞计数试剂盒-8(CCK-8)检测细胞活力和增殖。RNA 提取和实时定量聚合酶链反应(qRT-PCR)确定 GASL1 表达。
ROC 曲线分析表明,GASL1 下调可有效区分颅内动脉瘤患者与健康对照者。颅内动脉瘤患者的血 GASL1 和 TGF-β1 呈负相关,但健康人群无此相关性。GASL1 过表达促进了人血管平滑肌细胞(VSMC)的增殖,并下调了 TGF-β1 的表达,而外源性 TGF-β1 则降低了 VSMC 的增殖,但对 GASL1 的表达无影响。
新型 lncRNA GASL1 在颅内动脉瘤患者中表达下调,并通过靶向 TGF-β1 调节体外 VSMC 的增殖。