The role of a lncRNA (TCONS_00044595) in regulating pineal CLOCK expression after neonatal hypoxia-ischemia brain injury
The role of a lncRNA (TCONS_00044595) in regulating pineal CLOCK expression after neonatal hypoxia-ischemia brain injury
复制标题
lncRNA (TCONS_00044595) 在新生儿缺氧缺血性脑损伤后调节松果体 CLOCK 表达中的作用
DOI：
10.1016/j.bbrc.2020.05.047
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发表时间：
2020-07-12
影响因子：
3.1
通讯作者：
Ding, Xin
中科院分区：
文献类型：
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作者：
Li, Hong;Xu, Li-Xiao;Ding, Xin
新生儿缺氧缺血性脑损伤（hypoxic-ischemic brain damage，HIBD）的一个常见但常被忽视的特征是松果体功能障碍导致的昼夜节律紊乱。我们以前的工作表明，miRNA在HIBD后调节松果体中的关键昼夜节律基因中起重要作用[5，21]。在本研究中，我们试图通过使用RNA-Seq分析新生儿HIBD时松果体长非编码RNA（lncRNA）的表达变化来扩展我们的研究。在验证lncRNA的变化后，我们发现一种lncRNA：TCONS_00044595在松果体中高度富集，并表现出昼夜节律的表达模式。接下来，我们进行了生物信息学分析来预测lncRNA-miRNA调控网络，并鉴定了168种可能靶向lncRNA TCONS_00044595的miRNA。我们进一步验证了一种候选miRNA：miR-182（一种已知的调节松果体Clock表达的因子）和lncRNA TCONS_00044595之间的真正相互作用。最后，我们表明，抑制lncRNA TCONS_00044595减轻了OGD条件下培养的松果体细胞和体内HIBD后松果体中的CLOCK激活。因此，我们的研究揭示了新生儿HIBD后松果体功能障碍的病理生理学新机制。(C)2020爱思唯尔公司All rights reserved.
A common, yet often neglectable, feature of neonatal hypoxic-ischemic brain damage (HIBD) is circadian rhythm disorders resulted from pineal gland dysfunction. Our previous work demonstrated that miRNAs play an important role in regulating key circadian genes in the pineal gland post HIBD [5,21]. In current study, we sought out to extend our investigation by profiling expression changes of pineal long non-coding RNAs (lncRNAs) upon neonatal HIBD using RNA-Seq. After validating lncRNA changes, we showed that one lncRNA: TCONS_00044595 is highly enriched in the pineal gland and exhibits a circadian expression pattern. Next, we performed bioinformatic analysis to predict the lncRNA-miRNA regulatory network and identified 168 miRNAs that potentially targetlncRNA TCONS_00044595. We further validated the bona fide interaction between one candidate miRNA: miR-182, a known factor to regulate pineal Clock expression, and lncRNA TCONS_00044595. Finally, we showed that suppression of lncRNA TCONS_00044595 alleviated the CLOCK activation both in the cultured pinealocytes under OGD conditions and in the pineal gland post HIBD in vivo. Our study thus shed light into novel mechanisms of pathophysiology of pineal dysfunction post neonatal HIBD. (C) 2020 Elsevier Inc. All rights reserved.