Dysregulated long noncoding RNAs in the brainstem of the DBA/1 mouse model of SUDEP

Abstract

Background: Long noncoding RNAs (lncRNAs) play an important role in many neurological diseases. This study aimed to investigate differentially expressed lncRNAs and messenger RNAs (mRNAs) in the susceptibility gaining process of primed DBA/1 mice, a sudden unexpected death in epilepsy (SUDEP) model, to illustrate the potential role of lncRNAs in SUDEP. Methods: The Arraystar mouse lncRNA Microarray V3.0 (Arraystar, Rockville, MD) was applied to identify the aberrantly expressed lncRNAs and mRNAs between primed DBA/1 mice and normal controls. The differences were verified by qRT-PCR. We conducted gene ontology (GO), the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and coexpression analyses to explore the possible function of the dysregulated RNAs. Results: A total of 502 lncRNAs (126 upregulated and 376 downregulated lncRNAs) and 263 mRNAs (141 upregulated and 122 downregulated mRNAs) were dysregulated with P < 0.05 and a fold change over 1.5, among which Adora3 and Gstt4 were possibly related to SUDEP. GO analysis revealed that chaperone cofactor-dependent protein refolding and misfolded protein binding were among the top ten downregulated terms, which pointed to Hspa1a, Hspa2a and their related lncRNAs. KEGG analysis identified 28 upregulated and 10 downregulated pathways. Coexpression analysis showed fifteen dysregulated long intergenic noncoding RNAs (lincRNAs) and three aberrantly expressed antisense lncRNAs, of which AK012034 and NR_040757 are potentially related to SUDEP by regulating LMNB2 and ITPR1, respectively. Conclusions: LncRNAs and their coexpression mRNAs are dysregulated in the priming process of DBA/1 in the brainstem. Some of these mRNAs and lncRNAs may be related to SUDEP, including Adora3, Lmnb2, Hspa1a, Hspa1b, Itrp1, Gstt4 and their related lncRNAs. Further study on the mechanism of lncRNAs in SUDEP is needed.