Low expression of miR‑532‑3p contributes to cerebral ischemia/reperfusion oxidative stress injury by directly targeting NOX2

Li, Mao; Zuo, Meiling; Wang, Aiping; Tian, Ying; Dong, Li-Chen; Li, Taoming; Kuang, Da‐Bin; Song, Gui-Lin; Yang, Zhong‐Bao

doi:10.3892/mmr.2020.11325

Cited by 20 publications

(17 citation statements)

References 43 publications

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“… 33 miR‑532‑3p downregulation leads to oxidative stress injury following cerebral ischemia/reperfusion by targeting NOX2 directly. 34 In the present study, we also observed that the neuroprotective functions mediated by miR-126a-5p in ischemic brain injury were noticeably antagonized by NOX2 overexpression, suggesting NOX2 overexpression and its upstream regulator miR-126a-5p could synergistically modulate oxidative stress and apoptosis. Our results indicated that upregulated miR-126a-5p could suppress oxidative stress and apoptosis through targeting NOX2 directly.…”

Section: Discussionsupporting

confidence: 76%

MicroRNA-126a-5p Exerts Neuroprotective Effects on Ischemic Stroke via Targeting NADPH Oxidase 2

Yu¹,

Zhou²,

Yang³

et al. 2021

NDT

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Background Ischemic stroke is a destructive cerebrovascular disorder related to oxidative stress; NOX2 is a major source for ROS production; and miR-126a-5p is involved in several diseases, such as abdominal aortic aneurysm. We investigated the role of miR-126a-5p in regulating NOX2 in ischemic stroke. Methods MiR-126a-5p and NOX2 were examined in the brains of rats subjected to cerebral ischemia/reperfusion (I/R) by RT-PCR and Western blot. MiR-126a-5p agomir was delivered to examine the effects of miR-126a-5p on I/R injury. The neurological deficit, infarct volume, and brain water content were evaluated. NOX activity, ROS production, and MDA and SOD levels were detected to assess oxidative stress. H&E staining was used to examine cell state. Apoptosis was evaluated by TUNEL, caspase-3 activity, and cleaved-caspase-3 protein level. The relationship between miR-126a-5p and NOX2 was analyzed by bioinformatics and luciferase reporter assay. MiR-126a-5p mimic, miR-126a-5p inhibitor, or pcDNA-NOX2 were transfected in SH-SY5Y cells to further assess the effects of miR-126a-5p on OGD/R-induced cells injury. Results NOX2 was upregulated and miR-126a-5p was down-regulated in the brains of I/R rats. MiR-126a-5p agomir obviously reduced the neurological deficit, infarct volume, brain water content, oxidative stress, and apoptosis in I/R rats. MiR-126a-5p targeted NOX2 directly and regulated NOX2 negatively. Moreover, miR-126a-5p mimic elevated cell viability and inhibited oxidative stress and apoptosis in OGD/R-treated SH-SY5Y cells, while miR-126a-5p inhibitor had the opposite effects. NOX2 overexpression antagonized the protective effects of miR-126a-5p mimic on OGD/R-induced cell injury. Conclusion MiR-126a-5p is a novel potential target for ischemic stroke therapy due to its protection against cerebral I/R injury via directly targeting NOX2.

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Section: Discussionsupporting

confidence: 76%

MicroRNA-126a-5p Exerts Neuroprotective Effects on Ischemic Stroke via Targeting NADPH Oxidase 2

Yu¹,

Zhou²,

Yang³

et al. 2021

NDT

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“…It was recently reported that the miRNAs were involved in progression of CI/R [ 7 , 15 , 16 ]. In the present study, we found that the progression of CI/R is significantly suppressed by miR-27a-3p mimics.…”

Section: Discussionmentioning

confidence: 99%

“…MicroRNAs (miRNAs) are non-coding RNAs involved in the development of multiple diseases, including CI/R [ 4 – 6 ]. For instance, miR-532-3p downregulation is known to aggravate CI/R injury by targeting NOX2 [ 7 ], and Zuo et al showed that miR-652 could protect against CI/R injury through suppression of NOX2 [ 8 ]. In addition, MiR-27a-3p is reportedly involved in the progression of ischemia/reperfusion (I/R) injury [ 9 ], though the biological function of miR-27a-3p in CI/R remains unclear.…”

Section: Introductionmentioning

confidence: 99%

MiR-27a-3p suppresses cerebral ischemia-reperfusion injury by targeting FOXO1

Zhu

et al. 2021

Aging

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Cerebral ischemia-reperfusion (CI/R) injury is a serious complication when treating patients experiencing ischemic stroke. Although the microRNA miR-27a-3p reportedly participates in ischemia/reperfusion (I/R) injury, its actions in CI/R remain unclear. To mimic CI/R in vitro , HT22 cells were subjected to oxygen glucose deprivation/reoxygenation (OGD/R). The results indicate that OGD inhibited growth and induced apoptosis among HT22 cells. The apoptosis was accompanied by increases in activated caspases 3 and 9 and decreases in Bcl-2. Oxidative stress was also increased, as indicated by increases in ROS and malondialdehyde and decreases in glutathione and superoxide dismutase. In addition, OGD induced G1 arrest in HT22 cells with corresponding upregulation of FOXO1 and p27 Kip1, suggesting the cell cycle arrest was mediated by FOXO1/p27 Kip1 signaling. Notably, FOXO1 was found to be the direct target of miR-27a-3p in HT22 cells. MiR-27a-3p was downregulated in OGD/R-treated HT22 cells, and miR-27a-3p mimics partially or entirely reversed all of the in vitro effects of OGD. Moreover, miR-27a-3p agomir significantly alleviated the symptoms of CI/R in vivo in a rat model of CI/R. Thus, MiR-27a-3p appears to suppress CI/R injury by targeting FOXO1.

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“…An in vitro H9C2 cell H/R model was established following the methods of Mao et al to mimic myocardial ischemia reperfusion injury [ 16 ]. When cells grow to a 70% area of a plate, the DMEM culture was removed and cells were washed twice using PBS to remove the residual culture.…”

Section: Methodsmentioning

confidence: 99%

“…Luciferase reporter assay was performed following the methods of Mao et al to observe the interaction between PTEN and miR-129 [ 16 ]. A luciferase reporter gene plasmid (pGL6; Promega Corporation) was constructed and designated as PTEN-WT or PTEN-MU according to the sequence of 3′UTR of PTEN cloned into the plasmid whether it contains the wild-type (WT) binding sites of miR-129-5p“CAAAAAA” or mutant (MUT)“CAAGAAA”.…”

Section: Methodsmentioning

confidence: 99%

miR-129 Attenuates Myocardial Ischemia Reperfusion Injury by Regulating the Expression of PTEN in Rats

Dai

Jiang

et al. 2021

BioMed Research International

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PTEN/AKT signaling plays pivotal role in myocardial ischemia reperfusion injury (MIRI), and miRNAs are involved in the regulation of AKT signaling. This study was designed to investigate the interaction between miR-129 and PTEN in MIRI. A MIRI rat model and a hypoxia reoxygenation (H/R) H9C2 cell model were constructed to simulate myocardial infarction clinically. TTC staining, creatine kinase (CK) activity, TUNEL/Hoechst double staining, Hoechst staining and flow cytometer were used for evaluating myocardial infarction or cell apoptosis. miR-129 mimic transfection experiment and luciferase reporter gene assay were conducted for investigating the function of miR-129 and the interaction between miR-129 and PTEN, respectively. Real-time PCR and western blotting were performed to analyze the gene expression. Compared to the control, MIRI rats presented obvious myocardial infarction, higher CK activity, increased expression of caspase-3 and PTEN, decreased expression of miR-129, and insufficient AKT phosphorylation. Consistently, H/R significantly increased the apoptosis of H9C2 cells, concomitant with the downregulation of miR-129, upregulation of PTEN and caspase-3, and insufficient phosphorylation of AKT, while miR-129 mimic obviously inhibited the expression of PTEN and caspase-3, increased the AKT phosphorylation, and decreased the cell apoptosis. Additionally, miR-129 mimic obviously decreased the relative luciferase activity in H9C2 cells. To our best knowledge, this study firstly found that the low expression of miR-129 accelerates the myocardial cell apoptosis by directly targeting 3 ′ UTR of PTEN. miR-129 is an important biomarker for MIRI, as well as a potential therapy target.

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Low expression of miR‑532‑3p contributes to cerebral ischemia/reperfusion oxidative stress injury by directly targeting NOX2

Cited by 20 publications

References 43 publications

MicroRNA-126a-5p Exerts Neuroprotective Effects on Ischemic Stroke via Targeting NADPH Oxidase 2

MicroRNA-126a-5p Exerts Neuroprotective Effects on Ischemic Stroke via Targeting NADPH Oxidase 2

MiR-27a-3p suppresses cerebral ischemia-reperfusion injury by targeting FOXO1

miR-129 Attenuates Myocardial Ischemia Reperfusion Injury by Regulating the Expression of PTEN in Rats

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