Chen Shengcai, Wang Mengdie, Yang Hang, Mao Ling, He Quanwei, Jin Huijuan, Ye Zi-Ming, Luo Xue-Ying, Xia Yuan-Peng, Hu Bo
Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Biochem Biophys Res Commun. 2017 Mar 25;485(1):167-173. doi: 10.1016/j.bbrc.2017.02.043. Epub 2017 Feb 12.
Emerging studies have illustrated that LncRNAs TUG1 play critical roles in multiple biologic processes. However, the LncRNA TUG1 expression and function in ischemic stroke have not been reported yet. In this study, we found that LncRNA TUG1 expression was significantly up-regulated in brain ischemic penumbra from rat middle carotid artery occlusion (MCAO) model, while similar results were also observed in cultured neurons under oxygen-glucose deprivation (OGD) insult. Knockdown of TUG1 decreased the ratio of apoptotic cells and promoted cells survival in vitro, which may be regulated by the elevated miRNA-9 expression and decreased Bcl2l11 protein. Furthermore, TUG1 could directly interact with miR-9 and down-regulating miR-9 could efficiently reverse the function of TUG1 on the Bcl2l11 expression. In summary, our result sheds light on the role of LncRNA TUG1 as a miRNA sponge for ischemic stroke, possibly providing a new therapeutic target in stroke.
新兴研究表明,长链非编码RNA TUG1在多种生物学过程中发挥关键作用。然而,长链非编码RNA TUG1在缺血性脑卒中中的表达及功能尚未见报道。在本研究中,我们发现,在大鼠大脑中动脉闭塞(MCAO)模型的脑缺血半暗带中,长链非编码RNA TUG1的表达显著上调,而在氧糖剥夺(OGD)损伤的原代培养神经元中也观察到类似结果。敲低TUG1可降低体外培养细胞的凋亡率并促进细胞存活,这可能是通过上调miRNA-9表达和降低Bcl2l11蛋白水平来调控的。此外,TUG1可直接与miR-9相互作用,下调miR-9可有效逆转TUG1对Bcl2l11表达的影响。总之,我们的研究结果揭示了长链非编码RNA TUG1作为缺血性脑卒中的miRNA海绵的作用,可能为脑卒中提供新的治疗靶点。