CircRNA_0079586 and circRNA_RanGAP1 are involved in the pathogenesis of intracranial aneurysms rupture by regulating the expression of MPO

Abstract

Several circRNAs have been reported to be dysregulated in human endothelial cells through sponging miRNAs. Previous reports demonstrated that MPO not only contributed to the formation and rupture of cerebral aneurysm but was also correlated with the degenerative remodeling predisposition to saccular intracranial aneurysm wall rupture, although its underlying mechanisms remain to be explored. Microarray screening was performed to compare the differential expression of circRNAs in the endothelial cells collected from UIAs and RIAs patients. Luciferase assays were used to explore the regulatory relationship between circRNAs and miRNAs, and between miRNAs and their target genes. Microarray screening analysis found a batch of up-regulated circRNAs in the endothelial cells harvested from RIAs patients, including circRNA-0079586 and circRNA-RanGAP1. Luciferase assays revealed the suppressive role of miR-183-5p/miR-877-3p in the expression of circRNA-0079586/circRNA-RanGAP1/MPO. And the expression of circRNA-0079586 and circRNA-RanGAP1 was respectively suppressed by the overexpression of miR-183-5p and miR-877-3p. And both the transfection of miR-183-5p and miR-877-3p mimics suppressed the relative expression level of MPO mRNA. The expression of circRNA-0079586, circRNA-RanGAP1 and MPO was significantly activated in the endothelial cells collected from RIAs patients when compared with UIAs patients, whereas the expression of miR-183-5p and miR-877-3p was remarkably suppressed in the endothelial cells collected from RIAs patients when compared with UIAs patients. We further altered the expression of circRNA-0079586 and circRNA-RanGAP1 using siRNA and overexpression in HUVECS, and the expression of circRNA-0079586 and circRNA-RanGAP1 was significantly and negatively correlated with the expression of miR-183-5p and miR-877-3p, but positively correlated with the expression of MPO under different conditions. In this study, we established two MPO-modulating signaling pathways of circRNA_0079586/miR-183-5p/MPO and circRNA_RanGAP1/miR-877-3p/MPO. These two signaling pathways are involved in the pathogenesis of intracranial aneurysms rupture.

Circular RNA hsa_circ_0007990 as a blood biomarker for unruptured intracranial aneurysm with aneurysm wall enhancement

“…Inflammation is a vital pathological mechanism in IA rupture. Differentially expressed circRNAs related to IA have been shown to involve the inflammatory pathways and regulate the inflammatory gene expression through the circRNA-microRNA-mRNA axis ( 17 – 19 ). CircRNA_0079586 and circRNA_RanGAP1 in the endothelial cell of IA tissues were involved in the inflammatory response and IA rupture via miR-183-5p/myeloperoxidase and miR-877-3p/myeloperoxidase, respectively ( 17 ).…”

“…Differentially expressed circRNAs related to IA have been shown to involve the inflammatory pathways and regulate the inflammatory gene expression through the circRNA-microRNA-mRNA axis ( 17 – 19 ). CircRNA_0079586 and circRNA_RanGAP1 in the endothelial cell of IA tissues were involved in the inflammatory response and IA rupture via miR-183-5p/myeloperoxidase and miR-877-3p/myeloperoxidase, respectively ( 17 ). CircLIFR in the IA tissues regulated the proliferation, migration, invasion, and apoptosis of vascular smooth muscle cells via the axis of miR-1299 and kinase insert domain receptor ( 18 ).…”

Transcriptomic Studies on Intracranial Aneurysms

“…In two studies, in addition to vessels, peripheral blood samples were analyzed to investigate potential similarities between aneurysmal expression profiles and blood, searching for biomarkers of IA presence and/or rupture [ 22 , 30 ]. Three other studies comprised in vitro parts, which allowed to verify some findings from the expression analyses in vascular smooth-muscle cells [ 23 , 26 ] or endothelial cells’ cultures [ 31 ].…”

“…From non-coding RNAs, miRNAs were the most investigated class with or without a concomitant profiling of mRNAs [ 8 , 14 , 15 , 16 , 25 , 26 ]. In four studies, expression of lncRNAs was analyzed [ 16 , 17 , 20 , 30 ], and in two, circular RNA (circRNA) [ 22 , 31 ]. When mRNA expression was not directly measured, mRNA target prediction analysis was provided.…”

CircTAOK1 regulates high glucose induced inflammation, oxidative stress, ECM accumulation, and apoptosis in diabetic nephropathy via targeting miR‐142‐3p/SOX6 axis

“…6,7 Besides, circRNA has been reported in various biological processes, such as proliferation, metabolism and differentiation. 8,9 CircRNA TAO kinase 1 (circTAOK1, circ_0003928) has been identified to promote cell apoptosis and inflammation in DN by regulating miR-151-3p and Anxa2 levels. 10 However, the regulatory mechanism of circTAOK1 in DN remains more exploration.…”