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

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,...

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Autores principales: Chen, Deng, Zhu, Lina, Lin, Xin, Zhou, Dong, Liu, Ling
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8369804/
https://www.ncbi.nlm.nih.gov/pubmed/34404356
http://dx.doi.org/10.1186/s12864-021-07921-7
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author Chen, Deng
Zhu, Lina
Lin, Xin
Zhou, Dong
Liu, Ling
author_facet Chen, Deng
Zhu, Lina
Lin, Xin
Zhou, Dong
Liu, Ling
author_sort Chen, Deng
collection PubMed
description 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12864-021-07921-7.
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spelling pubmed-83698042021-08-18 Dysregulated long noncoding RNAs in the brainstem of the DBA/1 mouse model of SUDEP Chen, Deng Zhu, Lina Lin, Xin Zhou, Dong Liu, Ling BMC Genomics Research Article 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12864-021-07921-7. BioMed Central 2021-08-17 /pmc/articles/PMC8369804/ /pubmed/34404356 http://dx.doi.org/10.1186/s12864-021-07921-7 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research Article
Chen, Deng
Zhu, Lina
Lin, Xin
Zhou, Dong
Liu, Ling
Dysregulated long noncoding RNAs in the brainstem of the DBA/1 mouse model of SUDEP
title Dysregulated long noncoding RNAs in the brainstem of the DBA/1 mouse model of SUDEP
title_full Dysregulated long noncoding RNAs in the brainstem of the DBA/1 mouse model of SUDEP
title_fullStr Dysregulated long noncoding RNAs in the brainstem of the DBA/1 mouse model of SUDEP
title_full_unstemmed Dysregulated long noncoding RNAs in the brainstem of the DBA/1 mouse model of SUDEP
title_short Dysregulated long noncoding RNAs in the brainstem of the DBA/1 mouse model of SUDEP
title_sort dysregulated long noncoding rnas in the brainstem of the dba/1 mouse model of sudep
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8369804/
https://www.ncbi.nlm.nih.gov/pubmed/34404356
http://dx.doi.org/10.1186/s12864-021-07921-7
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