Dataset Information

MRNA, lncRNA, and circRNA expression profiles in a new aortic dissection murine modelinduced by hypoxia and Ang II

ABSTRACT: Background and aims: Aortic dissection (AD) is a cardiovascular emergency with degeneration of the aortic media. Mounting evidence indicates obstructive sleep apnea (OSA) as an independent risk factor for AD development with unknown mechanisms. This study aims to establish a stable murine model of OSA-related AD (OSA-AD) and uncover the potential changes in gene transcripts in OSA-AD. Materials and methods: ApoE-/- mice were exposed to the chronic intermittent hypoxia (CIH) system combined with Ang II administration to establish the OSA-AD model. Pathological staining was performed to exhibit the physiological structure of the mouse aorta. The SBC mouse ceRNA microarray was used to identify significantly differentially expressed (DE) mRNAs, DE long-non-coding RNAs (DElncRNAs), and DE circular RNAs (DEcircRNAs) in OSA-AD tissues. Subsequently, bioinformatics analysis, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genome (KEGG), and protein–protein interaction (PPI) analyses, was performed to evaluate the function of the significantly differentially expressed transcripts (DETs). The hub genes were confirmed using quantitative real-time polymerase chain reaction (qRT-PCR). Results: ApoE-/- mice exposed to CIH and Ang II showed a high ratio of aortic accident (73.33%) and significant aortic diameter dilatation (1.96 ± 0.175 mm). A total of 1,742 mRNAs, 2,625 lncRNAs, and 537 circRNAs were identified as DETs (LogFC ≥ 1.5 or ≤ –1.5, P < 0.05). GO and KEGG analyses demonstrated that the differentially expressed mRNAs (DEmRNAs) were most enriched in cell proliferation, migration, apoptosis, inflammation, and hypoxia-related terms, which are closely related to aortic structural homeostasis. The PPI network contained 609 nodes and 934 connections, the hub genes were highlighted with the CytoHubba plugin and confirmed by qRT-PCR in AD tissues. KEGG pathway analysis revealed that the cis-regulated genes of DElncRNAs and circRNAs-host genes were enriched in aortic structural homeostasis-related pathways. Conclusion: Our findings help establish a de novo OSA-AD animal model using ApoE-/- mice. Many DEmRNAs, DElncRNAs, and DEcircRNAs were screened for the first time in OSA-AD tissues. Our findings provide useful bioinformatics data for understanding the molecular mechanism of OSA-AD and developing potential therapeutic strategies for OSA-AD.

ORGANISM(S): Mus musculus

PROVIDER: GSE215935 | GEO | 2022/11/16

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Background: Microglia plays complex and crucial roles in multiple sclerosis (MS). This study aimed to explore the biological significance of microglia-associated genes in experimental autoimmune encephalomyelitis (EAE) . Methods: Differentially expressed genes (DEGs) were screened with six machine learning (ML) methods, which were also utilized to validate the microglia-associated DEGs in three public databases. ceRNA and Protein–protein interaction (PPI) network analyses were utilized to identify the interaction of the 6 novel biomarkers with other molecules. Then, CIBERSORT and single-sample gene set enrichment analysis (ssGSEA) were employed to quantify the relative abundance of each immune cell infiltration, respectively. qRT-PCR was performed to test the expression of key DEGs in murine models. Results: A total of 247 DEmRNA, 499 DElncRNAs and 269 DEcircRNAs were identified. With screening strategy of five ML algorithms, 6 DEmRNAs were obtained including NGP, HIST1H2BJ, PBLD1, MBLN3, CD180 and F10. Then the 6 DEmRNAs were used as a multigene signature to construct models to differentiate EAE from normal microglia, and AUC value for each model was greater than 0.8. The diagnostic value of these 6 DEmRNAs were identified and further verified by qRT-PCR. Then, differential expression for five out of these 6 DEmRNAs, namely NGP, HIST1H2BJ, PBLD1, MBLN3, and F10 were confirmed. Using PPI analysis, DEmRNAs frequently interacting with transcription factors (TFs), potential drugs and RBPs were identified. With immune cell infiltration analyses, we found EAE microglia presented high levels of immune infiltration, especially Nature Killer (NK) cells and CD8+ T cells. We also reported circRNA (circRNA_00638) was predicted to bind to 76 RBPs. Conclusions: We identified and validated 6 novel microglia related genes and developed a multigene signature with ML methods to confirm their ability to accurately diagnose and characterize biological alterations in EAE microglia. The six key DEmRNAs might also be latent targets for immunoregulatory therapy.

Dataset Information

MRNA, lncRNA, and circRNA expression profiles in a new aortic dissection murine modelinduced by hypoxia and Ang II

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets