RESEARCH ARTICLEOpen AccessGenome-wide microRNA changes in humanintracranial aneurysmsDehua Liu1†, Liang Han1†, Xiao Wu2, Xinjian Yang3, Qunye Zhang2*and Fan Jiang2*AbstractBackground: Intracranial aneurysms are pathological dilatations of the cerebral artery, while rupture of intracranialaneurysms causes life-threatening subarachnoid hemorrhage. The molecular mechanisms of pathogenesis ofintracranial aneurysms are poorly understood. MicroRNAs have fundamental roles in modulating vascular biologyand disease. In the present study, we carried out a genome-wide characterization on expressions of microRNAs, andperformed integrative analyses in conjunction with changes of the transcriptome in human intracranial aneurysms.Methods: Genome-wide microRNA screening was performed in 6 intracranial aneurysmal samples and 6 normalsuperficial temporal arteries. Each case and control pair was individually matched with gender, age (±5 years), andhigh blood pressure history. Microarray analysis was performed using Agilent Human miRNA arrays.Results: As compared to normal arteries, we identified 157 microRNAs that were differentially expressed in theaneurysmal tissue (P< 0.05 and fold change ≥2), including 72 upregulated and 85 downregulated. The changedmicroRNAs included endothelium-enriched microRNAs such as members of the let-7 family, miR-17, miR-23b,miR-126, hsa-miR-24-1 and miR-222, and vascular smooth muscle-enriched miRNAs such as miR-143 and miR-145.Moreover, miR-1, miR-10a, miR-125b, and miR-26a, which were implicated in modulating vascular smooth musclecell functions such as proliferation, apoptosis and shift of phenotype, were also changed. In contrast, microRNAsinvolved in monocyte and macrophage functions, such as miR-155, miR-146a, miR-223, and miR-124a, were notsignificantly changed. Bioinformatic analysis revealed that the changed microRNAs were associated with severalbiological processes related to aneurysm formation, including inflammation, dysregulation of extracellular matrix,smooth muscle cell proliferation, programmed cell death, and response to oxidative stress. Interestingly, we foundthat a subset of the potential microRNA target genes belonged to the protein translation machinery, includingvarious eukaryotic translation initiation factors and ribosomal proteins, and this finding was highly correlated withour previous transcriptome data showing that multiple genes of the ribosomal proteins and translation initiationand elongation factors were significantly downregulated in human intracranial aneurysms.Conclusions: Our results support that dysregulated microRNAs may have a pathogenic role in intracranialaneurysms. Disruption of the protein translation process may have a pathogenic role in the development ofintracranial aneurysms.Keywords: Intracranial aneurysm, microRNA, Microarray, Human, Cerebral vascular disease, System biology,Transcriptome, Protein translation machinery* Correspondence: maogou1974@gmail.com; fjiang@sdu.edu.cn†Equal contributors2Key Laboratory of Cardiovascular Remodeling and Function Research, QiluHospital, 107 Wenhuaxi Road, Jinan 250012, Shandong Province, ChinaFull list of author information is available at the end of the article© 2014 Liu et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the CreativeCommons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, andreproduction in any medium, provided the original work is properly credited. The Creative Commons Public DomainDedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article,unless otherwise stated.Liu et al. BMC Neurology 2014, 14:188http://www.biomedcentral.com/1471-2377/14/188
