CircUSP36 attenuates ischemic stroke injury through the miR-139-3p/SMAD3/Bcl2 signal axis.
Jialei YangWanting HeLian GuJianxiong LongLulu ZhuRuirui ZhangZhi ZhaoBingyi XuAruo NanLi SuPublished in: Clinical science (London, England : 1979) (2022)
Circular RNAs (circRNAs) play important roles in a variety of physiological and pathological processes. Researches demonstrated that circRNAs provided novel strategies for the prevention and treatment of IS. However, the biological function of hsa_circ_0045932 (circUSP36) has not been revealed yet. Here, we explored the effect of circUSP36 on IS and its mechanism. In the present study, we found that circUSP36 expression was significantly decreased in the peripheral blood of IS patients and was negatively correlated with the severity, infarct volume and poor prognosis of IS. Functionally, circUSP36 silencing inhibited cellular activity and proliferation and promoted apoptosis after oxygen-glucose deprivation/reperfusion (OGD/R) treatment, while circUSP36 overexpression reversed these cellular phenotypes in vitro. Adeno-associated virus (AAV)-mediated overexpression of circUSP36 attenuates brain injury and neurological deficit and promotes motor function recovery of transient middle cerebral artery occlusion (tMCAO) mice. Subsequently, the RNA antisense purification (RAP) and luciferase reporter assay confirmed that circUSP36 acts as a sponge to adsorb miR-139-3p, and miR-139-3p could bind and inhibit SMAD3 expression. Further rescue experiments showed that both miR-139-3p overexpression and SMAD3 silencing could abolish the antiapoptotic effect of circUSP36. In summary, we reveal for the first time that circUSP36 attenuates ischemic stroke injury through the miR-139-3p/SMAD3/Bcl2 signal axis, which make circUSP36 a potential therapeutic target for IS.
Keyphrases
- poor prognosis
- brain injury
- epithelial mesenchymal transition
- long non coding rna
- cerebral ischemia
- transforming growth factor
- middle cerebral artery
- subarachnoid hemorrhage
- peripheral blood
- end stage renal disease
- cell proliferation
- chronic kidney disease
- transcription factor
- atrial fibrillation
- signaling pathway
- newly diagnosed
- oxidative stress
- prognostic factors
- peritoneal dialysis
- single cell
- heart failure
- crispr cas
- cell death
- high throughput
- genome wide
- replacement therapy
- climate change
- combination therapy
- adipose tissue
- blood glucose
- coronary artery disease
- high fat diet induced
- patient reported outcomes
- acute ischemic stroke
- nucleic acid