Gao Ge, Zhang Yang, Yu Jian, Chen Yu, Gu Daqun, Niu Chaoshi, Fu Xianming, Wei Jianjun
Department of Neurosurgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, 17 Lu' jiang Road, Hefei, 230001, Anhui, People's Republic of China.
Department of Neurosurgery, Anhui Provincial Hospital Affiliated to Anhui Medical University, Hefei, Anhui, People's Republic of China.
Nanoscale Res Lett. 2020 Jun 29;15(1):139. doi: 10.1186/s11671-020-03357-2.
The roles of some long non-coding RNAs (lncRNAs) in intracranial aneurysm (IA) have been investigated in many studies. The aim of this study is to elucidate the mechanism of lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1)/microRNA-143 (miR-143)/vascular endothelial growth factor-A (VEGFA) signal axis in vascular endothelial injury-induced IA. MALAT1, miR-143, and VEGFA expression in IA tissues and normal arterial tissues were detected. Matrix metalloproteinase 9 (MMP-9) in tissues, von Willebrand factor (vWF) in serum and tissues, and endothelin-1 (ET-1) in serum were detected. The modeled IA rats were injected with silenced or overexpressed MALAT1 for detecting vascular endothelial injury. Vascular endothelial cells from patients with IA were abstracted and transfected with silenced or overexpressed MALAT1 to verify the impacts of MALAT1 on cell viability and apoptosis. The connections among MALAT1, miR-143, and VEGFA were verified by online prediction, luciferase activity, and RNA-pull down assays. Overexpression of MALAT1 and VEGFA and poor expression of miR-143 were found in IA tissues. Downregulation of MALAT1 inhibited blood pressure, the expression of ET-1, vWF, and MMP-9, as well as the apoptotic index of vascular endothelial cells of rats with IA. Downregulated MALAT1 inhibited apoptosis and promoted viability of vascular endothelial cells in IA. MALAT1 bound to miR-143 and miR-143 targeted VEGFA. This study suggests that MALAT1 elevates VEGFA expression through competitive binding to miR-143, thereby boosting apoptosis and attenuating viability of vascular endothelial cells in IA.
多项研究已对一些长链非编码RNA（lncRNA）在颅内动脉瘤（IA）中的作用进行了探究。本研究旨在阐明lncRNA转移相关的肺腺癌转录本1（MALAT1）/微小RNA-143（miR-143）/血管内皮生长因子-A（VEGFA）信号轴在血管内皮损伤诱导的IA中的作用机制。检测IA组织和正常动脉组织中MALAT1、miR-143和VEGFA的表达。检测组织中的基质金属蛋白酶9（MMP-9）、血清和组织中的血管性血友病因子（vWF）以及血清中的内皮素-1（ET-1）。对建立IA模型的大鼠注射沉默或过表达的MALAT1以检测血管内皮损伤。提取IA患者的血管内皮细胞并转染沉默或过表达的MALAT1，以验证MALAT1对细胞活力和凋亡的影响。通过在线预测、荧光素酶活性和RNA下拉实验验证MALAT1、miR-143和VEGFA之间的关系。发现IA组织中MALAT1和VEGFA过表达而miR-143表达不足。下调MALAT1可降低IA大鼠的血压、ET-1、vWF和MMP-9的表达以及血管内皮细胞的凋亡指数。下调MALAT1可抑制IA中血管内皮细胞的凋亡并促进其活力。MALAT1与miR-143结合，且miR-143靶向VEGFA。本研究表明，MALAT1通过与miR-143竞争性结合来提高VEGFA的表达，从而促进IA中血管内皮细胞的凋亡并减弱其活力。
