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.
Highlights
Abbreviations HUVECs Human umbilical endothelial cells IA Intracranial aneurysm RIAs Ruptured intracranial aneurysms UIAs Unruptured intracranial aneurysms wall shear stress (WSS) Wall shear stress TF Turbulent flow
In terms of how wall shear stress (WSS) causes aneurysm rupture, it is strongly believed that the absolute value of WSS alone may not be used to reasonably forecast the onset of aneurysm rupture, because it does not involve any type of directional information
Physiological researches have revealed that the endothelial cells of blood capillaries can respond to the changes in the direction as well as magnitude of WSS, and such responses may cause the onset of aneurysm re-modeling and additional growth and rupture of the aneurysm[7,14,15]
Summary
Abbreviations HUVECs Human umbilical endothelial cells IA Intracranial aneurysm RIAs Ruptured intracranial aneurysms UIAs Unruptured intracranial aneurysms WSS Wall shear stress TF Turbulent flow. While large size aneurysms have been thought to be associated with a higher risk of rupture, latest researches have shown that a lot of ruptured aneurysms are small in d imensions[8]. Physiological researches have revealed that the endothelial cells of blood capillaries can respond to the changes in the direction as well as magnitude of WSS, and such responses may cause the onset of aneurysm re-modeling and additional growth and rupture of the aneurysm[7,14,15]. CircRNA CDR1as is significantly overexpressed in tumor tissues, while the silencing of CDR1as hinders the development of tumors by targeting miRNA-720
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
