Microarray Profiling and Co-Expression Network Analysis of LncRNAs and mRNAs in Neonatal Rats Following Hypoxic-ischemic Brain Damage.

Fengyan Zhao,Yi Qu,Ruifeng Lu,Huiqing Wang,Li Zhang,Haiting Liu,Jing Gan,Yi Feng,Junyan Liu,Dezhi Mu

doi:10.1038/srep13850

Fengyan Zhao, Yi Qu + Show 8 more

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https://doi.org/10.1038/srep13850

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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.

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Long noncoding RNAs are currently thought to have vital and wide-raging functions, including mediating local and higher-order epigenetic states and modulating posttranscriptional RNA processing, transport, stabilization, metabolism, and translation[2,3]
At 24 h after HI injury, the animals were executed for microarray analysis of Long noncoding RNAs (lncRNAs) expression
A total of 5,067 lncRNAs was detected in the neonatal rat brain, 322 of which (6.35%) responded to HI brain injury with a fold change of at least 1.5 (P < 0 .05, Fig. 1A,C and Table 1 )

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Introduction

Long noncoding RNAs (lncRNAs) are currently thought to have vital and wide-raging functions, including mediating local and higher-order epigenetic states and modulating posttranscriptional RNA processing, transport, stabilization, metabolism, and translation[2,3]. Previous studies in the adult rat have shown that after stroke, cerebral lncRNA expression profiles are extensively altered and contribute to the stabilization of mRNA expression[11]. Few studies to date have evaluated lncRNA changes in developing brain after HI injury. To the best of our current knowledge, methods for the identification of novel disease-related lncRNAs includes microarray, qRT-PCR, RNA-seq and capture sequencing. We adopted a microarray analysis to detect the lncRNAs expression in developing brain following HIBD. Our results revealed that the expression profile of lncRNAs is dramatically different between HI brains and sham control. Silencing of lncRNA BC088414 attenuated HI injury with decreased levels of Casp[6] and Adrb[2]

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