Inhibition of <scp>microRNA</scp>‐9‐5p and <scp>microRNA</scp>‐128‐3p can inhibit ischemic stroke‐related cell death in vitro and in vivo

Yan, Qin; Sun, Shouyuan; Yuan, Shuai; Wang, Xiaoqing; Zhang, Zhenchang

doi:10.1002/iub.2357

Cited by 25 publications

(18 citation statements)

References 30 publications

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“…We also observed that upregulation of miR-124 by ago-miR-124 protected neurons against apoptotic cell death and improved behavioral performance by decreasing DAPK1 and apoptosisrelated proteins, including caspase-3 and cleaved caspase-3. A previous report by Yan et al (2020) demonstrated that miR-124 expression was significantly increased after OGD (Yan et al, 2020). This differs from our findings, possibly due to the use of primary cultured neurons vs. the N2a cells used by Yan et al (2020).…”

Section: Discussioncontrasting

confidence: 99%

“…A previous report by Yan et al (2020) demonstrated that miR-124 expression was significantly increased after OGD (Yan et al, 2020). This differs from our findings, possibly due to the use of primary cultured neurons vs. the N2a cells used by Yan et al (2020). Although the specific reason for the difference is unclear, our results were confirmed by the PIT-stroke model.…”

Section: Discussioncontrasting

confidence: 95%

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miR-124 Alleviates Ischemic Stroke-Induced Neuronal Death by Targeting DAPK1 in Mice

et al. 2021

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BackgroundIschemic stroke induces neuronal cell death and causes brain dysfunction. Preventing neuronal cell death after stroke is key to protecting the brain from stroke damage. Nevertheless, preventative measures and treatment strategies for stroke damage are scarce. Emerging evidence suggests that microRNAs (miRNAs) play critical roles in the pathogenesis of central nervous system (CNS) disorders and may serve as potential therapeutic targets.MethodsA photochemically induced thrombosis (PIT) mouse model was used as an ischemic stroke model. qRT-PCR was employed to assess changes in miRNAs in ischemic lesions of PIT-stroke mice and primary cultured neurons subjected to oxygen-glucose deprivation (OGD). 2,3,5-triphenyltetrazolium chloride (TTC) staining was performed to evaluate brain infarction tissues in vivo. TUNEL staining was employed to assess neuronal death in vitro. Neurological scores and motor coordination were investigated to evaluate stroke damage, including neurological deficits and motor function.ResultsIn vivo and in vitro results demonstrated that levels of miR-124 were significantly decreased following stroke, whereas changes in death-associated protein kinase 1 (DAPK1) levels exhibited the converse pattern. DAPK1 was identified as a direct target of miR-124. N-methyl-D-aspartate (NMDA) and OGD-induced neuronal death was rescued by miR-124 overexpression. Upregulation of miR-124 levels significantly improved PIT-stroke damage, including the overall neurological function in mice.ConclusionWe demonstrate the involvement of the miR-124/DAPK1 pathway in ischemic neuronal death. Our results highlight the therapeutic potential of targeting this pathway for ischemic stroke.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussioncontrasting

confidence: 95%

miR-124 Alleviates Ischemic Stroke-Induced Neuronal Death by Targeting DAPK1 in Mice

et al. 2021

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“…Data were expressed as mean AE standard deviation, and analyzed using one-way ANOVA, followed by Tukey's multiple comparisons test, **p < 0.01. fluid of stroke patients, and repression of miR-128 can reduce cell death and infarct volume. 22 miR-128 expression in patients with acute ischemic stroke is elevated with the aggravation of this disease. 23 Neurons are first directly affected by insufficient blood flow due to their inherent high energy requirements.…”

Section: Discussionmentioning

confidence: 97%

RETRACTED: Mechanism of ARPP21 antagonistic intron miR‐128 on neurological function repair after stroke

Chai

Zheng

2021

Ann Clin Transl Neurol

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Objective: Stroke is a cerebrovascular disorder that often causes neurological function defects. ARPP21 is a conserved host gene of miR-128 controlling neurodevelopmental functions. This study investigated the mechanism of ARPP21 antagonistic intron miR-128 on neurological function repair after stroke. Methods: Expressions of ARPP21 and miR-128 in stroke patients were detected. The mouse neurons and astrocytes were cultured in vitro and treated with oxygenglucose deprivation (OGD). The OGD-treated cells were transfected with pc-ARPP21 and miR-128 mimic. The proliferation of astrocytes, and the apoptosis of neurons and astrocytes were detected, and inflammatory factors of astrocytes were measured. The binding relationship between miR-128 and CREB1 was verified. The rat model of middle cerebral artery occlusion (MCAO) was established. ARPP21 expression in model rats was detected. The effects of pc-ARPP21 on neuron injury, brain edema volume, and cerebral infarct in rats were observed. Results: ARPP21 expression was downregulated and miR-128 expression was upregulated in stroke patients. pc-ARPP21 facilitated the proliferation of astrocytes and inhibited apoptosis of neurons and astrocytes, and reduced inflammation of astrocytes. miR-128 mimic could reverse these effects of pc-ARPP21 on neurons and astrocytes. miR-128 targeted CREB1 and reduced BDNF secretion. In vitro experiments confirmed that ARPP21 expression was decreased in MCAO rats, and pc-ARPP21 promoted neurological function repair after stroke. Conclusion: ARPP21 upregulated CREB1 and BDNF expressions by antagonizing miR-128, thus inhibiting neuronal apoptosis and promoting neurological function repair after stroke. This study may offer a novel target for the management of stroke.

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“… 39 Recent studies have revealed that miR-9-3p was significantly upregulated in cerebrospinal fluid of stroke patients compared with that of normal subjects. 12 , 14 , 40 However, the role and specific mechanisms of miR-375 in I/R-induced injury in the brain remains unclear. In agreement with a previous study finding that miR-9-3p was significantly elevated in the cerebrospinal fluid of stroke patients, 40 our study found that miR-9-3p was significantly upregulated in the I/R model, both in vitro and in vivo.…”

Section: Discussionmentioning

confidence: 99%

“… 12 , 14 , 40 However, the role and specific mechanisms of miR-375 in I/R-induced injury in the brain remains unclear. In agreement with a previous study finding that miR-9-3p was significantly elevated in the cerebrospinal fluid of stroke patients, 40 our study found that miR-9-3p was significantly upregulated in the I/R model, both in vitro and in vivo. Studies on embryonic stem cells imply that miR-9 plays a key role in neural fate determination in mammalian brain development.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-9-3p Aggravates Cerebral Ischemia/Reperfusion Injury by Targeting Fibroblast Growth Factor 19 (FGF19) to Inactivate GSK-3β/Nrf2/ARE Signaling

Zhou¹,

Yang²,

Chu³

et al. 2021

NDT

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Purpose MicroRNAs (miRNAs) are emerging as essential regulators in the development of cerebral ischemia/reperfusion (I/R) injury. This study aimed to explore the regulation of miR-9-3p on FGF19-GSK-3β/Nrf2/ARE signaling in cerebral I/R injury. Materials and Methods A mouse model with I/R injury was constructed by middle cerebral artery occlusion (MCAO) and an HT22 cell model was established by oxygen-glucose deprivation/reperfusion (OGD/R). The expression of miR-9-3p was detected by RT-qPCR. Protein expression of fibroblast growth factor 19 (FGF19), cleaved caspase-3, and GSK-3β signaling-related proteins (p-GSK-3β and Nrf2) were detected by Western blot. Cell viability was assessed by MTT assay. Oxidative stress was detected by commercial kits. The target of miR-9-3p was predicted by TargetScan and confirmed by luciferase reporter assay. The effects of miR-9-3p on GSK-3β/Nrf2/ARE signaling were assessed by rescue experiments. Results MiR-9-3p was significantly upregulated in brain tissues of MCAO/R-treated mice and OGD/R-treated HT22 cells. Downregulation of miR-9-3p attenuated infarct volume and neurological outcomes of MCAO/R-treated mice in vivo and OGD/R-induced cell injury and oxidative stress in vitro, while overexpression of miR-9-3p showed the opposite effects. MiR-9-3p directly bound to the 3′-untranslated region of FGF19 and negatively regulated its expression. Inhibition of miR-9-3p enhanced GSK-3β/Nrf2/ARE signaling-mediated antioxidant response, while this effect was partially eliminated by FGF19 or Nrf2 silencing. Conclusion Our study suggests that inhibition of miR-9-3p protects against cerebral I/R injury through activating GSK-3β/Nrf2/ARE signaling-mediated antioxidant responses by targeting FGF19, providing a potential therapeutic target for ischemic stroke.

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Inhibition of microRNA‐9‐5p and microRNA‐128‐3p can inhibit ischemic stroke‐related cell death in vitro and in vivo

Cited by 25 publications

References 30 publications

miR-124 Alleviates Ischemic Stroke-Induced Neuronal Death by Targeting DAPK1 in Mice

miR-124 Alleviates Ischemic Stroke-Induced Neuronal Death by Targeting DAPK1 in Mice

RETRACTED: Mechanism of ARPP21 antagonistic intron miR‐128 on neurological function repair after stroke

MicroRNA-9-3p Aggravates Cerebral Ischemia/Reperfusion Injury by Targeting Fibroblast Growth Factor 19 (FGF19) to Inactivate GSK-3β/Nrf2/ARE Signaling

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