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Updated: Sep 24, 2025
Author Spotlight: Establishing a Reliable Distal MCA Occlusion Model in Mice for Stroke Research
Published on: December 15, 2023
CircUSP36 attenuates ischemic stroke injury through the miR-139-3p/SMAD3/Bcl2 signal axis
Jialei Yang1,2, Wanting He1,2, Lian Gu3
1School of Public Health, Guangxi Medical University, 22 Shuangyong Road, Nanning 530021, Guangxi, China.
Insights
Circular RNAs (circUSP36) are decreased in ischemic stroke (IS) patients. circUSP36 protects against IS by regulating the miR-139-3p/SMAD3/Bcl2 pathway, offering a potential therapeutic target.
Area of Science:
- Biochemistry
- Molecular Biology
- Neuroscience
Background:
- Circular RNAs (circRNAs) are crucial in physiological and pathological processes.
- circRNAs offer novel therapeutic strategies for ischemic stroke (IS).
- The specific role of hsa_circ_0045932 (circUSP36) in IS remains largely unknown.
Purpose of the Study:
- To investigate the function and mechanism of circUSP36 in ischemic stroke (IS).
- To explore circUSP36 as a potential therapeutic target for IS.
Main Methods:
- Quantitative analysis of circUSP36 expression in IS patients.
- In vitro studies using oxygen-glucose deprivation/reperfusion (OGD/R) models.
- In vivo studies using adeno-associated virus (AAV)-mediated circUSP36 overexpression in transient middle cerebral artery occlusion (tMCAO) mice.
- RNA antisense purification (RAP) and luciferase reporter assays to identify molecular interactions.
Main Results:
- circUSP36 expression is significantly reduced in IS patients and correlates with disease severity.
- circUSP36 overexpression protects against OGD/R-induced cellular damage in vitro.
- circUSP36 overexpression improves neurological function and motor recovery in tMCAO mouse models.
- circUSP36 acts as a molecular sponge for miR-139-3p, inhibiting its interaction with SMAD3.
- The circUSP36/miR-139-3p/SMAD3 pathway influences apoptosis via Bcl2.
Conclusions:
- circUSP36 plays a protective role in ischemic stroke.
- circUSP36 exerts its neuroprotective effects by modulating the miR-139-3p/SMAD3/Bcl2 signaling axis.
- circUSP36 represents a promising therapeutic target for ischemic stroke treatment.
Abstract:
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.
