The role of miR-182 in regulating pineal CLOCK expression after hypoxia-ischemia brain injury in neonatal rats
The role of miR-182 in regulating pineal CLOCK expression after hypoxia-ischemia brain injury in neonatal rats
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miR-182对新生大鼠缺氧缺血性脑损伤后松果体CLOCK表达的调节作用
DOI：
10.1016/j.neulet.2015.02.026
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发表时间：
2015-03-30
影响因子：
2.5
通讯作者：
Feng, Xing
中科院分区：
文献类型：
--
作者：
Ding, Xin;Sun, Bin;Feng, Xing
昼夜节律紊乱是新生儿缺氧缺血性脑损伤（HIBD）引起的一种常见神经功能缺损。然而，对其潜在机制知之甚少。我们先前的研究显示，新生儿HIBD后，松果体中的时钟基因在蛋白质水平而非mRNA水平上显著升高。为了研究生物钟基因的转录后调控机制，我们使用高通量芯片筛选新生儿HIBD后松果体中miRNA水平的变化。在表达显著下调的miRNA中，我们鉴定了一种靶向Clock的3 '-非翻译区（3'-UTR）的miRNA（miR 182），该基因是Clock基因的关键组成部分，并且在原代培养的松果体细胞中在氧-葡萄糖剥夺后调节CLOCK表达中起关键作用。因此，我们的研究结果提供了新的见解的治疗目标的研究新生儿缺氧缺血性脑损伤后的昼夜节律紊乱。(C)2015爱思唯尔爱尔兰有限公司版权所有。
Circadian rhythm disorder is a common neurological deficit caused by neonatal hypoxic-ischemic brain damage (HIBD). However, little is known about its underlying mechanisms. Our previous studies revealed a significant elevation of clock genes at the protein, but not mRNA, levels in the pineal gland after neonatal HIBD. To investigate the mechanisms of post-transcriptional regulation on clock genes, we screened changes of miRNA levels in the pineal gland after neonatal HIBD using high-throughput arrays. Within the miRNAs whose expression was significantly down-regulated, we identified one miRNA (miR182) that targeted the 3'-untranslated region (3'-UTR) of Clock, a key component of clock genes, and played a crucial role in regulating CLOCK expression after oxygen-glucose deprivation in primarily cultured pinealocytes. Our findings therefore provide new insight on studies of therapeutic targets for circadian rhythm disturbance after neonatal HIBD. (C) 2015 Elsevier Ireland Ltd. All rights reserved.