Identification and functional analysis of microRNAs in rats following focal cerebral ischemia injury

Duan, Xianchun; Gan, Jianghua; Peng, Daiyin; Bao, Qiuyu; Xiao, Ling; Wei, Liangbing; Wu, Jian

doi:10.3892/mmr.2019.10073

Cited by 14 publications

(11 citation statements)

References 53 publications

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“…Through using starBase software, we predicted the candidate miRNA targets of GAS5. Among all these predicted targets, six miRNAs were screened out due to their vital roles in regulating cerebral ischemia-reperfusion injury, including miR-34b-3p, 13 miR-485-3p, 16 miR-211-5p, 17 miR-217-5p, 18 miR-874-3p 19 and miR-338-5p. 20 We tested the regulatory relationships between GAS5 and these candidate targets.…”

Section: Resultsmentioning

confidence: 99%

LncRNA GAS5 Silencing Attenuates Oxygen-Glucose Deprivation/Reperfusion-Induced Injury in Brain Microvascular Endothelial Cells via miR-34b-3p-Dependent Regulation of EPHA4

Shen¹,

Wang²,

Xu³

et al. 2021

NDT

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Background:The aim of our study was to explore the role of long non-coding RNA (lncRNA) growth arrest-specific 5 (GAS5) in ischemic stroke using oxygen-glucose deprivation/reperfusion (OGD/R)-induced bEnd.3 cells as in vitro cell model. Methods: Real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot assay were adopted to analyze RNA and protein expression. Cell viability and apoptosis were analyzed by Cell Counting Kit-8 (CCK8) assay and flow cytometry. The levels of nitric oxide (NO) and endothelin-1 (ET-1) in culture supernatant were examined by their matching commercial kits. The intermolecular target interaction was predicted by starBase software and tested by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. Results: OGD/R-induced apoptosis and dysregulation in vascular endocrine system were largely alleviated by the knockdown of GAS5. GAS5 interacted with microRNA-34b-3p (miR-34b-3p), and GAS5 silencing protected bEnd.3 cells from OGD/R-induced injury partly through up-regulating miR-34b-3p. EPH receptor A4 (EPHA4) was a target of miR-34b-3p. GAS5 acted as the molecular sponge of miR-34b-3p to up-regulate EPHA4 in bEnd.3 cells. GAS5 interference protected against OGD/R-induced damage in bEnd.3 cells partly through down-regulating EPHA4. Conclusion: LncRNA GAS5 knockdown protected brain microvascular endothelial cells bEnd.3 from OGD/R-induced injury depending on the regulation of miR-34b-3p/EPHA4 axis.

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Section: Resultsmentioning

confidence: 99%

LncRNA GAS5 Silencing Attenuates Oxygen-Glucose Deprivation/Reperfusion-Induced Injury in Brain Microvascular Endothelial Cells via miR-34b-3p-Dependent Regulation of EPHA4

Shen¹,

Wang²,

Xu³

et al. 2021

NDT

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“…miR-6328 was identified as a rat-specific miRNA derived from intronic regions of chromosome 20 and its functions are unknown ( Clokie et al, 2012 ). On the other hand, the expression of miR-10b-3p , conserved across rodents and humans, is increased in rat brains undergoing stress-induced depression or decreased in rats exposed to cold stress and in regions of brain damage following ischemia ( Zhen et al, 2017 ; Duan et al, 2019 ; Fang et al, 2020 ). Even though no link between miR-10b-3p and epilepsy has been established so far, the 5p strand of miR-10b is linked to epilepsy.…”

Section: Discussionmentioning

confidence: 99%

Enrichment of Circular RNA Expression Deregulation at the Transition to Recurrent Spontaneous Seizures in Experimental Temporal Lobe Epilepsy

et al. 2021

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Mesial temporal lobe epilepsy (mTLE) is a common form of epilepsy and is characterized by recurrent spontaneous seizures originating from the temporal lobe. The majority of mTLE patients develop pharmacoresistance to available anti-epileptic drugs (AEDs) while exhibiting severe pathological changes that can include hippocampal atrophy, neuronal death, gliosis and chronic seizures. The molecular mechanisms leading to mTLE remain incompletely understood, but are known to include defects in post-transcriptional gene expression regulation, including in non-coding RNAs (ncRNAs). Circular RNAs (circRNAs) are a class of recently rediscovered ncRNAs with high levels of expression in the brain and proposed roles in diverse neuronal processes. To explore a potential role for circRNAs in epilepsy, RNA-sequencing (RNA-seq) was performed on hippocampal tissue from a rat perforant pathway stimulation (PPS) model of TLE at different post-stimulation time points. This analysis revealed 218 differentially expressed (DE) circRNAs. Remarkably, the majority of these circRNAs were changed at the time of the occurrence of the first spontaneous seizure (DOFS). The expression pattern of two circRNAs, circ_Arhgap4 and circ_Nav3, was further validated and linked to miR-6328 and miR-10b-3p target regulation, respectively. This is the first study to examine the regulation of circRNAs during the development of epilepsy. It reveals an intriguing link between circRNA deregulation and the transition of brain networks into the state of spontaneous seizure activity. Together, our results provide a molecular framework for further understanding the role and mechanism-of-action of circRNAs in TLE.

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“…As a member of the miR-183 gene cluster, the normal expression of miR-183-5p is important for nervous system function ( 30 ). A previous study has revealed that 17 miRNAs, including miR-183-5p, were downregulated in infarcted brain areas following focal cerebral ischemia in rats according to microRNA sequencing compared with healthy tissues ( 31 ). The results of the present study demonstrated decreased levels of miR-183-5p in MCAO models of cerebral ischemia injury and OGD-treated N2A cells compared with those in the respective control groups.…”

Section: Discussionmentioning

confidence: 99%

miR‑183‑5p attenuates cerebral ischemia injury by negatively regulating PTEN

Zhu

Zhou

et al. 2020

Mol Med Rep

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cerebral ischemia is a common cerebrovascular disease caused by the occlusion of a cerebral blood vessel. Micrornas (mirnas/mirs) are emerging regulators of various human diseases, including cerebral ischemia. upregulation of mir-183-5p has been reported to alleviate liver injury induced by ischemia-reperfusion (i/r). However, the effect of mir-183-5p on cerebral ischemia injury remains unknown. The present study evaluated the effects of mir-183-5p on ischemia injury using ischemic models of mouse brains exposed to transient middle cerebral artery occlusion and neuro-2a (n2a) neuroblastoma cells exposed to oxygen-glucose-deprivation (oGd) and subsequently reoxygenated. ischemia was evaluated in mice using neurological function scores, cerebral edema, 2,3,5-triphenyltetrazoliumchloride, nissl and Fluoro-Jade B staining assays. in addition, mir-183-5p expression, n2a cell viability and the expression levels of apoptosis-associated proteins were detected by quantitative Pcr, cell counting Kit-8 assay, flow cytometry and western blotting. The association between mir-183-5p and phosphatase and tensin homolog (PTEN) was also confirmed by a luciferase reporter assay. The results revealed that mir-183-5p expression was decreased and brain damage was increased in ischemic mice compared with the sham group. additionally, mir-183-5p levels were reduced, and apoptosis was increased in n2a cells exposed to ischemia compared with the control group. Following transfection with agomir-183-5p, cerebral ischemic injury and apoptosis levels were reduced in the in vivo i/r stroke model and oGd-induced n2a cells. in addition, PTen was determined to be a target of mir-183-5p following elucidation of a direct binding site. overexpression of PTen reversed the mir-183-5p-induced n2a cell apoptosis inhibition and survival after oGd. The results of the present study suggested that mir-183-5p reduced ischemic injury by negatively regulating PTen, which may aid the development of a novel therapeutic strategy for cerebral ischemia.

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Identification and functional analysis of microRNAs in rats following focal cerebral ischemia injury

Cited by 14 publications

References 53 publications

LncRNA GAS5 Silencing Attenuates Oxygen-Glucose Deprivation/Reperfusion-Induced Injury in Brain Microvascular Endothelial Cells via miR-34b-3p-Dependent Regulation of EPHA4

LncRNA GAS5 Silencing Attenuates Oxygen-Glucose Deprivation/Reperfusion-Induced Injury in Brain Microvascular Endothelial Cells via miR-34b-3p-Dependent Regulation of EPHA4

Enrichment of Circular RNA Expression Deregulation at the Transition to Recurrent Spontaneous Seizures in Experimental Temporal Lobe Epilepsy

miR‑183‑5p attenuates cerebral ischemia injury by negatively regulating PTEN

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