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

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

doi:10.1038/srep13850

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

Sci Rep. 2015 Sep 9:5:13850. doi: 10.1038/srep13850.

Authors

Fengyan Zhao^{1

2}, Yi Qu^{1

2}, Junyan Liu³, Haiting Liu^{1

2}, Li Zhang^{1

2}, Yi Feng^{1

2}, Huiqing Wang^{1

2}, Jing Gan^{1

2}, Ruifeng Lu^{1

2}, Dezhi Mu^{1

2

4}

Affiliations

¹ Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu 610041, China.
² Key Laboratory of Obstetric &Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, Sichuan University, Chengdu 610041, China.
³ Department of Pediatrics, Binzhou Medical University Hospital, Binzhou 256600, China.
⁴ Department of Pediatrics, University of California, San Francisco, CA94143, USA.

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Animals, Newborn
Apoptosis / genetics
Cell Proliferation
Cluster Analysis
Computational Biology / methods
Gene Expression Profiling*
Gene Expression Regulation*
Gene Knockdown Techniques
Gene Ontology
Gene Regulatory Networks*
Hypoxia-Ischemia, Brain / genetics*
Hypoxia-Ischemia, Brain / metabolism
Open Reading Frames
RNA, Long Noncoding / genetics*
RNA, Messenger / genetics*
Rats
Reproducibility of Results
Signal Transduction
Time Factors
Transcriptome*

Substances

RNA, Long Noncoding
RNA, Messenger