Microarray Profiling and Co-Expression Network Analysis of LncRNAs and mRNAs in Neonatal Rats Following Hypoxic-ischemic Brain Damage.
Microarray Profiling and Co-Expression Network Analysis of LncRNAs and mRNAs in Neonatal Rats Following Hypoxic-ischemic Brain Damage.
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缺氧缺血性脑损伤后新生大鼠 LncRNA 和 mRNA 的微阵列分析和共表达网络分析
DOI：
10.1038/srep13850
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发表时间：
2015-09-09
影响因子：
4.6
通讯作者：
Mu D
中科院分区：
文献类型：
--
作者：
Zhao F;Qu Y;Liu J;Liu H;Zhang L;Feng Y;Wang H;Gan J;Lu R;Mu D
长链非编码RNA（lncRNA）在细胞内稳态中起着关键作用。然而，很少有人知道他们的作用，在发育中的大鼠大脑缺氧缺血性脑损伤（HIBD）。为了探讨lncRNA在HIBD中的表达和功能，我们利用基因芯片分析了lncRNA在缺氧缺血（HI）脑和假手术对照脑中的表达谱。结果表明，HI组与假手术组的lncRNA含量有显著差异。与假手术对照组相比，共发现322种lncRNA在HI脑中差异表达。其中，BC088414是上调最显著的lncRNA之一。此外，375个编码基因在HI脑和假手术对照之间差异表达。通路和基因本体分析表明，上调的编码基因主要参与创伤、炎症和防御，而下调的转录本主要与神经发生和修复有关。此外，编码非编码共表达网络分析表明，BC088414 lncRNA的表达与乳腺癌相关基因，包括Casp6和Adrb2相关。在PC12细胞中，lncRNA BC088414的沉默导致Casp6和Adrb2的mRNA水平降低，细胞凋亡减少，细胞增殖增加。这些结果表明lncRNA可能通过调节编码基因参与HIBD的发病机制。
Long noncoding RNAs (lncRNAs) play critical roles in cellular homeostasis. However, little is known about their effect in developing rat brains with hypoxic-ischemic brain damage (HIBD). To explore the expression and function of lncRNA in HIBD, we analyzed the expression profiles of lncRNAs in hypoxic-ischemic (HI) brains and sham control using microarray analysis. The results showed a remarkable difference in lncRNA between HI and sham brains. A total of 322 lncRNAs were found to be differentially expressed in HI brains, compared to sham control. Among these, BC088414 was one of the most significantly urpregulated lncRNAs. In addition, 375 coding genes were differentially expressed between HI brains and sham control. Pathway and gene ontology analysis indicated that the upregulated coding genes mostly involved in wounding, inflammation and defense, whereas the downregulated transcripts were largely associated with neurogenesis and repair. Moreover, coding non-coding co-expression network analysis showed that the BC088414 lncRNA expression was correlated with apoptosis-related genes, including Casp6 and Adrb2. Silencing of lncRNA BC088414 in PC12 cells caused reduced mRNA level of Casp6 and Adrb2, decreased cell apoptosis and increased cell proliferation. These results suggested lncRNA might participate in the pathogenesis of HIBD via regulating coding genes.