CircUSP36 attenuates ischemic stroke injury through the miR-139-3p/SMAD3/Bcl2 signal axis

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 this 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.

A crosstalk between circular RNA, microRNA, and messenger RNA in the development of various brain cognitive disorders

“…The crosstalk between circRNA, miRNA, and mRNA (or proteins) through one or more circRNA–miRNA–mRNA networks indicates the complicated and dynamic mechanisms of brain cognitive disorders including AD (Zhao et al, 2016 ; Lu et al, 2019 ; Yang et al, 2019 ; Zhu et al, 2020 ; Li et al, 2022 ; Pan et al, 2022 ; Xu X. et al, 2022 ), PD (Kumar et al, 2018 ; Feng et al, 2020 ; Wang et al, 2021 ; Liu et al, 2022 ; Zhang et al, 2022 ), TBI (Chen et al, 2019 ; Li H. et al, 2020 ; Huang X. J. et al, 2022 ; Zheng et al, 2022 ), stroke (Bai et al, 2018 ; Han et al, 2018 ; Zhou et al, 2021 ; Guo et al, 2022 ; Huang et al, 2022 ; Xu T. et al, 2022 ; Yang H. et al, 2022 ; Yang J. et al, 2022 ), and POND (Gao et al, 2020 ) ( Table 1 ). In summary, circRNAs act as sponging-like roles in transcription and posttranscription in the novel regulation processes of gene expression.…”

“…Hypoxic pretreated adipose-derived stem cell (ADSC) exosome improves cognitive function by decreasing neuronal damage and shifting microglia from an M1 to M2 phenotype in the hippocampus of AIS via circRps5/miR-124-3p/SIRT7 axes (Yang H. et al, 2022 ). CircUSP36 attenuates ischemic stroke injury through the miR-139-3p/SMAD3/Bcl2 signal axis (Yang J. et al, 2022 ). The ratio of serum circRNA-284 to miR-221 may serve as a diagnostic biomarker of carotid plaque rupture and stroke with an AUC of 0.98 (95% CI: 0.96–1.00) (Bazan et al, 2017 ).…”

Hsa_circ_0008870 suppresses bone formation of growth plate through inhibition of miR-185-3p/ MAPK1 axis in idiopathic short stature

“…Circular RNAs are found in stable forms in human peripheral blood, according to recent studies, and the expression of circRNAs in blood may contain disease-related information ( Memczak et al, 2015 ; Zhang et al, 2020 ; Yang et al, 2022 ). For example, Yang et al discovered that the patients with ischemic stroke had significantly reduced expression of circUSP36 in their peripheral blood, and it alleviated the injury of ischemic stroke injury via miR-139-3p/SMAD3 axis ( Yang et al, 2022 ). circPPM1F is evidently upregulated in peripheral blood of children with type 1 diabetes mellitus, and overexpression of circPPM1F can promote islet injury by enhancing the activation of M1 macrophages ( Zhang et al, 2020 ).…”

Three Dimensional-Arterial Spin Labeling Evaluation of Improved Cerebral Perfusion After Limb Remote Ischemic Preconditioning in a Rat Model of Focal Ischemic Stroke

“…A total of 40 patients aged 50–80 years with acute ischemic stroke (AIS), some of whom received LRP intervention in advance ( Ho et al, 2020 ), underwent MRI sequences including conventional MRI, diffusion-weighted imaging (DWI), magnetic resonance angiography (MRA), and ASL data from January 2020 to December 2020 were reviewed retrospectively. For all the patients, according to different conditions, the corresponding treatment plan should be selected, such as regular treatment, intravenous alteplase treatment (IVT), and endovascular treatment (EVT) ( Yang et al, 2022 ). Patients who received only regular treatment or received both regular treatment and LRP intervention were assigned to regular treatment and regular treatment + LRP groups, respectively.…”