CircRNA CTNNB1 (circCTNNB1) ameliorates cerebral ischemia/reperfusion injury by sponging miR-96-5p to up-regulate scavenger receptor class B type 1 (SRB1) expression

Abstract

Emerging studies show that circRNA catenin beta 1 (circCTNNB1) plays a critical role in cancer. However, the expression and function of circCTNNB1 in cerebral ischemia/reperfusion injury (IRI) have not been reported. The present study discovered that circCTNNB1 and scavenger receptor class B type 1 (SRB1) expression levels were significantly down-regulated in mouse astrocytes (mAS) treated with oxygen glucose deprivation and reperfusion (OGD/R), and similar results were observed in a mouse middle cerebral artery occlusion model. Overexpression of circCTNNB1 alleviated cell apoptosis, oxidative stress and the inflammatory response induced by OGD/R in vitro . Up-regulation of circCTNNB1 increased SRB1 expression levels to protect mAS cells from OGD/R-induced damage. CircCTNNB1 and SRB1 interacted with miR-96-5p, and the overexpression of miR-96-5p efficiently reversed the function of circCTNNB1 in OGD/R-treated mAS cells. CircCTNNB1 protected against cerebral ischemia-reperfusion injury by up-regulating SRB1 in vivo . In conclusion, our findings suggest that circCTNNB1 acts as a competitive endogenous RNA for miR-96-5p to alleviate cerebral IRI, which provides novel evidence that circCTNNB1 and SRB1 may be biomarkers and therapeutic targets for cerebral IRI.

Circular RNAs: Promising Treatment Targets and Biomarkers of Ischemic Stroke

“…Moreover, pro-inflammatory factors in the cells were suppressed, mitigating the inflammatory response. Therefore, circCTNNB1 mitigates post-stroke oxidative stress and inflammatory response through the miR-96–5p/SRB1 axis [ 59 ].…”

Circular RNAs in organ injury: recent development

“…Traumatic brain injury circLphn3 downregulated Improved BBB integrity and promoted inflammatory response [43] circLrp1b downregulated Inhibits inflammatory response [45] circHtra1 upregulated Inhibits cell proliferation and promotes cell apoptosis [46] Ischemia/reperfusion injury circCTNNB1 downregulated Improves BBB integrity and promotes cell proliferation [50] circFOXO3 upregulated Promotes autophagy and maintains BBB integrity [51] circCCDC9 downregulated Improves BBB integrity [52] circUCK2 downregulated Inhibits cell proliferation and promotes cell apoptosis [53] circCDC14A upregulated Promotes cell proliferation and migration [56] circUSP36 downregulated Inhibits cell apoptosis and promoted cell proliferation [31] Spinal cord Spinal cord injury circHIPK3 downregulated Inhibits cell proliferation and promotes cell apoptosis [60] circRNA_7079 upregulated Promotes inflammatory response [63] circRNA_2960 upregulated Promotes inflammatory response and inhibits cell apoptosis [65] Visceral organ…”

CircCRIM1/microRNA‐141‐3p/thioredoxin‐binding protein axis mediates neuronal apoptosis after cerebral ischemia‐reperfusion

“…CircTLK1 aggravates neuronal injury and neurological deficits after ischemic stroke via miR‐335‐3p/TIPARP 7 . Furthermore, circCTNNB1 is reported to ameliorate CIR injury by sponging miR‐96‐5p to upregulate SRB1 expression 10 . Therefore, studying the latent molecular mechanisms of circRNA will help to discover therapeutic targets or strategies for CIR.…”

“…7 Furthermore, circCTNNB1 is reported to ameliorate CIR injury by sponging miR-96-5p to upregulate SRB1 expression. 10 Therefore, studying the latent molecular mechanisms of circRNA will help to discover therapeutic targets or strategies for CIR. CircCRIM1 is a circRNA derived from exons 2, 3, and 4 of CRIM1 gene.…”