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The role of a lncRNA (TCONS_00044595) in regulating pineal CLOCK expression after neonatal hypoxia-ischemia brain injury.
Biochemical and Biophysical Research Communications ( IF 3.1 ) Pub Date : 2020-05-22 , DOI: 10.1016/j.bbrc.2020.05.047 Hong Li 1 , Li-Xiao Xu 2 , Jian Yu 1 , Lanlan Tan 1 , Po Miao 1 , Xiaofeng Yang 1 , Qiuyan Tian 2 , Mei Li 2 , Chen-Xi Feng 2 , Yuanyuan Yang 3 , Ning Sha 4 , Xing Feng 1 , Bin Sun 1 , Min Gong 1 , Xin Ding 1
Biochemical and Biophysical Research Communications ( IF 3.1 ) Pub Date : 2020-05-22 , DOI: 10.1016/j.bbrc.2020.05.047 Hong Li 1 , Li-Xiao Xu 2 , Jian Yu 1 , Lanlan Tan 1 , Po Miao 1 , Xiaofeng Yang 1 , Qiuyan Tian 2 , Mei Li 2 , Chen-Xi Feng 2 , Yuanyuan Yang 3 , Ning Sha 4 , Xing Feng 1 , Bin Sun 1 , Min Gong 1 , Xin Ding 1
Affiliation
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.
中文翻译:
lncRNA(TCONS_00044595)在调节新生儿缺氧缺血性脑损伤后松果体CLOCK表达中的作用。
新生儿缺氧缺血性脑损伤(HIBD)的常见但通常可以忽略的特征是松果体功能障碍导致的昼夜节律障碍。我们以前的工作表明,miRNA在HIBD后调节松果体关键昼夜节律基因中起着重要作用[5,21]。在当前的研究中,我们寻求通过使用RNA-Seq对新生HIBD上的松果体长非编码RNA(lncRNA)的表达变化进行分析来扩展我们的研究范围。验证lncRNA的变化后,我们显示了一个lncRNA:TCONS_00044595在松果体中高度富集,并显示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以预测lncRNA-miRNA调控网络,并鉴定了168个可能靶向lncRNA TCONS_00044595的miRNA。我们进一步验证了一种候选miRNA之间的真正相互作用:调控松果体时钟表达的已知因子miR-182和lncRNA TCONS_00044595。最后,我们表明抑制lncRNA TCONS_00044595可以减轻OGD条件下培养的松果细胞和体内HIBD后松果体中CLOCK的激活。因此,我们的研究揭示了新生儿HIBD后松果功能障碍的病理生理新机制。
更新日期:2020-05-22
中文翻译:
lncRNA(TCONS_00044595)在调节新生儿缺氧缺血性脑损伤后松果体CLOCK表达中的作用。
新生儿缺氧缺血性脑损伤(HIBD)的常见但通常可以忽略的特征是松果体功能障碍导致的昼夜节律障碍。我们以前的工作表明,miRNA在HIBD后调节松果体关键昼夜节律基因中起着重要作用[5,21]。在当前的研究中,我们寻求通过使用RNA-Seq对新生HIBD上的松果体长非编码RNA(lncRNA)的表达变化进行分析来扩展我们的研究范围。验证lncRNA的变化后,我们显示了一个lncRNA:TCONS_00044595在松果体中高度富集,并显示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以预测lncRNA-miRNA调控网络,并鉴定了168个可能靶向lncRNA TCONS_00044595的miRNA。我们进一步验证了一种候选miRNA之间的真正相互作用:调控松果体时钟表达的已知因子miR-182和lncRNA TCONS_00044595。最后,我们表明抑制lncRNA TCONS_00044595可以减轻OGD条件下培养的松果细胞和体内HIBD后松果体中CLOCK的激活。因此,我们的研究揭示了新生儿HIBD后松果功能障碍的病理生理新机制。