Expression profile of long noncoding RNAs in human cerebral aneurysms: a microarray analysis

Abstract

OBJECTIVE The pathogenesis of cerebral aneurysms (CAs) remains largely unknown. Long noncoding RNAs (lncRNAs) were reported recently to play crucial roles in many physiological and biological processes. Here, the authors compared the gene-expression profiles of CAs and their control arteries to investigate the potential functions of lncRNAs in the formation of CAs. METHODS A prospective case-control study was designed to identify the changes in expression of lncRNAs and mRNAs between 12 saccular CA samples (case group) and 12 paired superficial temporal artery samples (control group). Microarray analysis was performed to investigate the expression of lncRNAs and messenger RNAs (mRNAs), and reverse-transcription quantitative polymerase chain reaction was used to validate the microarray analysis findings. Then, an lncRNA target-prediction program and gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were applied to explore potential lncRNA functions. RESULTS A comparison between the case and control groups revealed that 1518 lncRNAs and 2545 mRNAs were expressed differentially. By using target-prediction program analysis, the authors constructed a complex network consisting of 2786 matched lncRNA-mRNA pairs, in which ine1 mRNA was potentially targeted by one to tens of lncRNAs, and vice versa. The results of further gene ontology and KEGG pathway analyses indicated that lncRNAs were involved mainly in regulating immune/inflammatory processes/pathways and vascular smooth muscle contraction, both of which are known to have crucial pathobiological relevance in terms of CA formation. CONCLUSIONS By comparing CAs with their control arteries, the authors created an expression profile of lncRNAs in CAs and propose here their possible roles in the pathogenesis of CAs. The results of this study provide novel insight into the mechanisms of CA pathogenesis and shed light on developing new therapeutic intervention for CAs in the future.

Keywords: CA = cerebral aneurysm; CCL5 = chemokine ligand 5; GO = gene ontology; KEGG = Kyoto Encyclopedia of Genes and Genomes; RT-qPCR = reverse-transcription quantitative polymerase chain reaction; SAH = subarachnoid hemorrhage; SMC = smooth muscle cell; STA = superficial temporal artery; cerebral aneurysms; inflammation; lncRNA = long non-coding RNA; long noncoding RNA; mRNA = messenger RNA; pathogenesis; vascular disorders; vascular smooth muscle contraction.