Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, China.
Key Laboratory of Neuro-oncology in Liaoning Province, Shenyang, China.
Cell Death Dis. 2019 Jun 5;10(6):441. doi: 10.1038/s41419-019-1631-0.
Long noncoding RNAs, a subgroup of noncoding RNAs, are implicated in ischemic brain injury. The expression levels of Snhg8, miR-384, Hoxa13, and FAM3A were measured in chronic cerebral ischemia-induced HT22 cells and hippocampal tissues. The role of the Snhg8/miR-384/Hoxa13/FAM3A axis was evaluated in chronic cerebral ischemia models in vivo and in vitro. In this study, we found that Snhg8 and Hoxa13 were downregulated, while miR-384 was upregulated in chronic cerebral ischemia-induced HT22 cells and hippocampal tissues. Overexpression of Snhg8 and Hoxa13, and silencing of miR-384, all inhibited chronic cerebral ischemia-induced apoptosis of HT22 cells. Moreover, Snhg8 bound to miR-384 in a sequence-dependent manner and there was a reciprocal repression between Snhg8 and miR-384. Besides, overexpression of miR-384 impaired Hoxa13 expression by targeting its 3'UTR and regulated chronic cerebral ischemia-induced neuronal apoptosis. Hoxa13 bound to the promoter of FAM3A and enhanced its promotor activity, which regulated chronic cerebral ischemia-induced neuronal apoptosis. Remarkably, the in vivo experiments demonstrated that Snhg8 overexpression combined with miR-384 knockdown led to an anti-apoptosis effect. These results reveal that the Snhg8/miR-384/Hoxa13/FAM3A axis plays a critical role in the regulation of chronic cerebral ischemia-induced neuronal apoptosis.
长链非编码 RNA 是一类非编码 RNA，其参与了脑缺血损伤。在慢性脑缺血诱导的 HT22 细胞和海马组织中检测 Snhg8、miR-384、Hoxa13 和 FAM3A 的表达水平。评估了 Snhg8/miR-384/Hoxa13/FAM3A 轴在体内和体外慢性脑缺血模型中的作用。在这项研究中，我们发现 Snhg8 和 Hoxa13 在慢性脑缺血诱导的 HT22 细胞和海马组织中表达下调，而 miR-384 表达上调。Snhg8 和 Hoxa13 的过表达以及 miR-384 的沉默均抑制慢性脑缺血诱导的 HT22 细胞凋亡。此外，Snhg8 以序列依赖性方式与 miR-384 结合，Snhg8 和 miR-384 之间存在相互抑制。此外，miR-384 通过靶向其 3'UTR 抑制 Hoxa13 的表达，调节慢性脑缺血诱导的神经元凋亡。Hoxa13 与 FAM3A 启动子结合并增强其启动子活性，调节慢性脑缺血诱导的神经元凋亡。值得注意的是，体内实验表明 Snhg8 过表达结合 miR-384 敲低可发挥抗凋亡作用。这些结果表明，Snhg8/miR-384/Hoxa13/FAM3A 轴在调节慢性脑缺血诱导的神经元凋亡中起关键作用。
