Dataset Information

MicroRNA/mRNA profiling and regulatory network of intracranial aneurysm.

ABSTRACT: BACKGROUND: Intracranial aneurysm (IA) is one of the most lethal forms of cerebrovascular diseases characterized by endothelial dysfunction, vascular smooth muscle cell phenotypic modulation, inflammation and consequently loss of vessel cells and extracellular matrix degradation. Besides environmental factors, genetics seem to be a very important factor in the genesis of this disease. Previous mRNA expression studies revealed a large number of differentially expressed genes between IA and control tissue. However, microRNAs (miRNA), small non-coding RNAs which are post-transcriptional regulators of gene expression, have been barely studied. Studying miRNAs could provide a hypothetical mechanism underlying rupture of IA. METHODS: A microarray study was carried out to determine difference in microRNAs and mRNA between patients' IA tissues and controls. Quantitative RT-PCR assay compared the expression level between two groups (14 IA domes vs. 14 controls) were used for validation. Validated miRNAs were analyzed using Ingenuity Pathway Analysis (IPA) to identify the networks and pathways. RESULTS: 18 miRNAs were confirmed by qPCR to be robustly down-regulated in 14 ruptured IA patients including hsa-mir-133b, hsa-mir-133a, hsa-mir-1, hsa-mir-143-3p, hsa-mir-145-3p, hsa-mir-145-5p, hsa-mir-455-5p, hsa-mir-143-5p, hsa-mir-23b-3p etc., of which 11 miRNAs are clusters: hsa-mir-1/has-mir-133a, hsa-mir-143/hsa-mir-145, hsa-mir-23b/hsa-mir-24-1, and hsa-mir-29b-2/hsa-mir-29c. 12 predicted functions were generated using IPA which showed significant associations with migration of phagocytes, proliferation of mononuclear leukocytes, cell movement of mononuclear leukocytes, cell movement of smooth muscle cells etc. CONCLUSION: These data support common disease mechanisms that may be under miRNA control and provide exciting directions for further investigations aimed at elucidating the miRNA mechanisms and targets that may yield new therapies for IA.

SUBMITTER: Jiang Y

PROVIDER: S-EPMC3849943 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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MicroRNA/mRNA profiling and regulatory network of intracranial aneurysm.

Jiang Yugang Y Zhang Mingming M He Hua H Chen Jia J Zeng Hua H Li Jia J Duan Ranhui R

BMC medical genomics 20130930

<h4>Background</h4>Intracranial aneurysm (IA) is one of the most lethal forms of cerebrovascular diseases characterized by endothelial dysfunction, vascular smooth muscle cell phenotypic modulation, inflammation and consequently loss of vessel cells and extracellular matrix degradation. Besides environmental factors, genetics seem to be a very important factor in the genesis of this disease. Previous mRNA expression studies revealed a large number of differentially expressed genes between IA and ...[more]

PMID: 24079748

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Project description:Intracranial aneurysm (IA) is a severe clinical condition of primary concern and currently, there is no effective therapeutic reagent. The present study aimed to investigate the molecular mechanism of IA via bioinformatic analysis. Various gene expression profiles (GSE26969) were downloaded from the Gene Expression Omnibus database, including 3 IA and 3 normal superficial temporal artery samples. Firstly, the limma package in R language was used to identify differentially expressed genes (DEGs; P?value <0.01 and |log2 FC|?1). Secondly, the database for annotation, visualization and integrated discovery software was utilized to perform pathway and functional enrichment analyses (false discovery rate ?0.05). Finally, protein?protein interaction (PPI) network and sub?network clustering analyses were performed using the biomolecular interaction network database and ClusterONE software, respectively. Following this, a transcription factor regulatory network was identified from the PPI network. A total of 1,124 DEGs were identified, of which 989 were upregulated and 135 downregulated. Pathway and functional enrichment analyses revealed that the DEGs primarily participated in RNA splicing, functioning of the spliceosome, RNA processing and the mRNA metabolic process. Following PPI network analysis, 1 hepatocyte nuclear factor (HNF) 4A (transcription factor)?centered regulatory network and 5 DEG?centered sub?networks were identified. On analysis of the transcription factor regulatory network, 6 transcription factors (HNF6, HNF4A, E2F4, YY1, H4 and H31T) and a regulatory pathway (HNF6?HNF4?E2F4) were identified. The results of the present study suggest that activating transcription factor?5, Jun proto?oncogene, activator protein?1 transcription factor subunit, HNF6, HNF4 and E2F4 may participate in IA progression via vascular smooth muscle cell apoptosis, inflammation, vessel wall remodeling and damage and the tumor necrosis factor?? signaling pathway. However, further experimental studies are required to validate these predictions.

Dataset Information

MicroRNA/mRNA profiling and regulatory network of intracranial aneurysm.

Publications

MicroRNA/mRNA profiling and regulatory network of intracranial aneurysm.

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