Silencing of lncRNA XLOC_035088 Protects Middle Cerebral Artery Occlusion-Induced Ischemic Stroke by Notch1 Signaling

Abstract

Ischemic stroke represents one of the leading causes of mortality worldwide and especially in developing countries. It is crucial for finding effective therapeutic targets that protect the brain against ischemic injury. Long noncoding RNAs (lncRNAs) have emerged as major regulators of neurological diseases, and clarifying their roles in cerebral ischemic injury may provide novel targets for the treatment of ischemic stroke. We aimed to investigate the role of lncRNA-XLOC_035088 in middle cerebral artery occlusion (MCAO)-induced rat brain injury and oxygen-glucose deprivation (OGD)-reperfusion treated hippocampal neurons. In our findings, we found that XLOC_035088 expression was significantly upregulated in OGD-reperfusion treated hippocampal neurons and in different brain regions of MCAO-treated rats. XLOC_035088 silencing protected against MCAO-induced ischemic brain injury in vivo and OGD-induced hippocampal neuronal apoptosis in vitro. Intrahippocampal silencing of XLOC_035088 significantly decreased brain XLOC_035088 expression, reduced brain infarct size, and improved neurological function through inhibiting NOTCH1 following derepression of presenilin 2 (PSEN2). Taken together, this study provides evidence that the lncRNA XLOC_035088/PSEN2/Notch1 axis is involved in the pathogenesis of ischemic brain injury, and presents a promising therapeutic route for ischemic stroke.

Long Non-Coding RNA-Mediated Competing Endogenous RNA Networks in Ischemic Stroke: Molecular Mechanisms, Therapeutic Implications, and Challenges

“…Furthermore, the LncRNA AK038897/miR-26a-5p/death-associated protein kinase 1 (DAPK1), FGD5 antisense RNA 1 (FGD5-AS1)/miRNA-223/insulin-like growth factor (IGF)-1 receptor (IGF1R), tumor-associated LncRNA expressed on chromosome 2 (TALNEC2)/miR-650/apoptotic peptidase activating factor 1 (APAF1), FOXD3-AS1/miR-765/BCL2L13, and RNA imprinted and accumulated in nucleus (Rian)/miR-144-3p/GATA3 axes have been found to attenuate apoptosis after cerebral I/R injury ( Zhang XQ. et al, 2019 ; Wei et al, 2019 ; Lu et al, 2020 ; Yao et al, 2020 ; Chen M. et al, 2021 ; Cao et al, 2021 ).…”