IDENTIFICATION OF CIRCULAR RNAS IN CEREBRAL ISCHEMIC STROKE

Cerebral Ischemic Stroke (CIS), caused by insufficient cerebral blood flow and subsequent oxygen deprivation, remains a leading cause of mortality and long-term neurological disability worldwide. Recent literature has highlighted the dysregulation of circular RNAs (circRNAs) in various diseases; however, the specific roles of circRNAs in CIS remain largely unclear and require further investigation.
Given that cardiac and cerebral ischemia share common hypoxia-induced signaling pathways, including oxidative stress and dysregulated cell survival, publicly available RNA sequencing data from patients with ischemic heart disease (IHD) were used as a discovery platform to identify ischemia-associated circRNAs potentially relevant to cerebrovascular ischemic injury. Our analysis identified circCIS as a potential candidate, showing upregulated expression in the ICA-positive patient group compared to the ICA-negative group.
CircCIS, composed of five exons from its host gene, predominantly localizes to the cytoplasm. Interestingly, we found that knockdown of circCIS in hCMEC/D3 cells significantly altered the expression of genes related to antioxidant defense and cell death, and reduced ROS levels. Furthermore, Transcriptome analysis of hCMEC/D3 cells depleted of circCIS indicated that the knockdown of circCIS primarily regulates cell survival and structural remodeling pathways. To explore the underlying mechanisms, we predicted potential miRNA partners and target mRNAs of circCIS.
In conclusion, we demonstrate that circCIS may regulate cell survival and oxidative stress responses in hCMEC/D3 cells through the circRNA/miRNA/mRNA axis, suggesting that circCIS may represent a promising molecular target and diagnostic biomarker for the development of novel therapeutic strategies in cerebrovascular ischemic disease.