Li Jie, Wang Ning, Nie Huan, Wang Shan, Jiang Tongtong, Ma Xuehan, Liu Wenjuan, Tian Kuo
Department of Neurology, The Second Affiliated Hospital of Harbin Medical University, Heilongjiang Province, Harbin, 150081, China.
Mol Neurobiol. 2022 May;59(5):2808-2821. doi: 10.1007/s12035-021-02632-2. Epub 2022 Feb 25.
Much efforts have been made to probe the mechanism underlying ischemic stroke (IS). This study was proposed to uncover the role of long non-coding RNA rhabdomyosarcoma 2 related transcript (RMST) in IS through microRNA-221-3p (miR-221-3p)/phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1)/transforming growth factor-β (TGF-β) axis. Neurological behavioral function, pathological changes in brain tissue, oxidative stress, and inflammation responses in middle cerebral artery occlusion (MCAO) mice were tested. RMST, miR-221-3p, PIK3R1, and TGF-β signaling-related protein expression in brain tissues of MCAO mice were detected. RMST and PIK3R1 were elevated, miR-221-3p was downregulated, and TGF-β pathway was activated in mice after MCAO. Restored miR-221-3p or depleted RMST improved neurological behavioral functions, relieved pathological injury in brain tissue, and repressed oxidative stress and inflammation in mice after MCAO. Depleted PIK3R1 or restored miR-221-3p offsets the negative effects of overexpressed RMST on mice with MCAO. The present work highlights that RMST augments IS through reducing miR-221-3p-mediated regulation of PIK3R1 and activating TGF-β pathway.
人们已经做出了很多努力来探究缺血性中风（IS）的潜在机制。本研究旨在通过微小RNA-221-3p（miR-221-3p）/磷酸肌醇-3-激酶调节亚基1（PIK3R1）/转化生长因子-β（TGF-β）轴揭示长链非编码RNA横纹肌肉瘤2相关转录本（RMST）在缺血性中风中的作用。检测了大脑中动脉闭塞（MCAO）小鼠的神经行为功能、脑组织病理变化、氧化应激和炎症反应。检测了MCAO小鼠脑组织中RMST、miR-221-3p、PIK3R1和TGF-β信号相关蛋白的表达。MCAO后小鼠体内RMST和PIK3R1升高，miR-221-3p下调，TGF-β通路激活。恢复miR-221-3p或敲低RMST可改善MCAO后小鼠的神经行为功能，减轻脑组织病理损伤，抑制氧化应激和炎症反应。敲低PIK3R1或恢复miR-221-3p可抵消过表达RMST对MCAO小鼠的负面影响。目前的研究强调，RMST通过减少miR-221-3p介导的对PIK3R1的调节并激活TGF-β通路来加重缺血性中风。
