Protective effect of DLX6-AS1 silencing against cerebral ischemia/reperfusion induced impairments.
Protective effect of DLX6-AS1 silencing against cerebral ischemia/reperfusion induced impairments.
复制标题
DLX6-AS1沉默对脑缺血/再灌注损伤的保护作用
DOI：
10.18632/aging.104070
复制
发表时间：
2020-11-18
期刊：
影响因子：
--
通讯作者：
Yuan Q
中科院分区：
文献类型：
--
作者：
Hu X;Xiang Z;Zhang W;Yu Z;Xin X;Zhang R;Deng Y;Yuan Q
在本研究中，我们探讨了远端缺失同源异型盒6反义1(DLX6-AS1)在卒中所致脑损伤中的作用。DLX6-AS1在小鼠脑缺血再灌流(I/R)时表达上调，DLX6-AS1表达下调可减轻脑I/R所致的急性损伤和远期神经功能损害。此外，在体内和体外，沉默DLX6-AS1显著减少神经细胞的凋亡。此外，抑制miRNA-149-3p可促进细胞的凋亡，证实DLX6-AS1可以海绵结合miR-149-3p。最后利用TargetScanVert软件预测BOK为miR-149-3P的靶标。在体内和体外，DLX6-AS1的沉默抑制了BOK的表达，而miR-149-3P抑制剂则逆转了这一作用。同时，BOK可促进OGD/R诱导的N2a细胞凋亡。因此，提示DLX6-AS1对miR-149-3p的海绵作用可能通过上调凋亡的BOK活性而导致脑神经元I/R损伤，为卒中损伤的治疗提供了新的途径。
In the present study, we investigated the role of lncRNA mus distal-less homeobox 6 antisense 1 (DLX6-AS1) during cerebral impairment induced by stroke. DLX6-AS1 levels were upregulated during ischemia/reperfusion (I/R) and downregulation of DLX6-AS1 reduced acute injury and ameliorated long-term neurological impairments induced by cerebral I/R in mice. Additionally, silencing of DLX6-AS1 significantly decreased the neuronal apoptosis in vivo and in vitro. Furthermore, inhibition of miRNA-149-3p led to enhance the apoptosis, which confirmed that DLX6-AS1 could sponge miR-149-3p. Finally, BOK was predicted to be the target of miR-149-3p using TargetScanVert software. And the silencing of DLX6-AS1 inhibited BOK expression both in vivo and in vitro, which was reversed by a miR-149-3p inhibitor. At meantime, BOK promoted OGD/R induced apoptosis in N2a cells. Therefore, this suggests that miR-149-3p sponging by DLX6-AS1 may lead to cerebral neuron I/R-induced impairments through upregulation of apoptotic BOK activity, which offers a new approach to the treatment of stroke impairment.
登录
查看更多内容
影响因子：
16
作者：
Cajigas I;Chakraborty A;Swyter KR;Luo H;Bastidas M;Nigro M;Morris ER;Chen S;VanGompel MJW;Leib D;Kohtz SJ;Martina M;Koh S;Ay F;Kohtz JD
通讯作者：
Kohtz JD
影响因子：
9
作者：
Carberry S;D'Orsi B;Monsefi N;Salvucci M;Bacon O;Fay J;Rehm M;McNamara D;Kay EW;Prehn JHM
通讯作者：
Prehn JHM
影响因子：
5
作者：
Zheng, Wen-xia;Cao, Xiao-lu;Hu, Xia-min
通讯作者：
Hu, Xia-min
影响因子：
3.7
作者：
Tan, Yan;Xiao, Di;Wang, Chenhong
通讯作者：
Wang, Chenhong
影响因子：
3.9
作者：
Yan, Tingxu;Sun, Yingying;Jia, Ying
通讯作者：
Jia, Ying