Long Non-coding RNAs as Promising Therapeutic Approach in Ischemic Stroke: a Comprehensive Review

Wolska, Marta; Jarosz-Popek, Joanna; Junger, Eva; Wicik, Zofia; Porshoor, Tahmina; Sharif, Lucia; Czajka, Pamela; Postuła, Marek; Mirowska‐Guzel, Dagmara; Członkowska, Anna; Eyileten, Ceren

doi:10.1007/s12035-020-02206-8

Cited by 35 publications

(21 citation statements)

References 99 publications

(114 reference statements)

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“…Previous studies have predominantly focused on elucidating changes in protein levels after cerebral ischemia ( Feng et al, 2017 ; Lee et al, 2017 ). In recent years, studies have increasingly focused on the key role of non-coding RNAs in ischemia ( Tiedt and Dichgans, 2018 ; Wolska et al, 2020 ). As a major component of non-coding RNAs, miRNAs in the CNS play important roles in neurogenesis, development, and maintenance of neuronal phenotype ( Kaur et al, 2013 ; Yapijakis, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

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: Discussionmentioning

confidence: 99%

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

et al. 2021

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“…In the last decades, non-coding RNAs including long non-coding RNAs (lncRNAs) and miRNAs have become promising therapeutic targets in ischemic stroke. 28 , 29 In the present study, we explored the role and underlying molecular mechanism of miR-195-5p in cerebral I/R injury, expecting to provide novel insights into stroke treatment. We found that low expression levels of miR-195-5p were closely associated with cerebral I/R injury both in vivo and in vitro.…”

Section: Discussionmentioning

confidence: 99%

MiR-195-5p Ameliorates Cerebral Ischemia-Reperfusion Injury by Regulating the PTEN-AKT Signaling Pathway

Ren¹,

Wang²,

Guo³

2021

NDT

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Background MiR-195-5p has been shown to play crucial roles in tumor inhibition, but its biological functions in cerebral ischemia-reperfusion (I/R) injury are unclear. Methods To mimic cerebral I/R injury, mice were induced by transient middle cerebral artery occlusion (MCAO). Human brain microvascular endothelial cells (HBMVECs) were treated with oxygen-glucose deprivation (OGD) to mimic I/R injury in vitro. The expression of miR-195-5p and PTEN was detected by qRT-PCR or Western blot. Cell viability was evaluated by CCK-8 assay. Cell apoptosis was detected by flow cytometer. Cell death was detected using specific lactate dehydrogenase (LDH) cytotoxicity kit. Infarct volume in mice brains was evaluated by TTC staining. Histopathological analysis was performed by HE staining and TUNEL staining. The interaction between miR-195-5p and PTEN was determined by TargetScan and luciferase reporter assay. Results MiR-195-5p was significantly downregulated and PTEN was upregulated during cerebral I/R injury both in vitro and in vivo. Overexpression of miR-195-5p efficiently enhanced cell viability, while reduced LDH release and apoptotic rate of OGD-treated HBMVECs in vitro. MiR-195-5p could negatively regulate the expression of PTEN by directly binding to its 3′-UTR. Overexpression of PTEN obviously attenuated the protective effect of miR-195-5p mimics on cell viability, LDH release and apoptosis in OGD-treated HBMVECs. Meanwhile, overexpression of miR-195-5p increased the expression levels of p-AKT in OGD-treated HBMVECs, while this effect was reversed by overexpression of PTEN. Moreover, overexpression of miR-195-5p efficiently ameliorated brain injury of mice after MCAO treatment in vivo. Conclusion Overexpression of miR-195-5p ameliorated cerebral I/R injury by regulating the PTEN-AKT signaling pathway, providing a potential therapeutic target for cerebral I/R injury.

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“…The majority of lncRNAs that have been identified and characterized have been in diseases. This include cancers (Jin et al, 2020;Teppan et al, 2020;Zhou et al, 2020;Katsushima et al, 2021), diabetes (Taheri et al, 2020;Xu E. et al, 2020;Ismail et al, 2021), cardiovascular diseases (Fang et al, 2020;Meng et al, 2020;Yeh et al, 2020) and ischemic stroke (Gan et al, 2021;Wolska et al, 2021). In this section, we will focus on angiogenic lncRNAs enriched in disease and their epigenetic functions.…”

Section: Angiogenic Lncrnas In Diseasementioning

confidence: 99%

Epigenetic Regulation of the Vascular Endothelium by Angiogenic LncRNAs

2021

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The functional properties of the vascular endothelium are diverse and heterogeneous between vascular beds. This is especially evident when new blood vessels develop from a pre-existing closed cardiovascular system, a process termed angiogenesis. Endothelial cells are key drivers of angiogenesis as they undergo a highly choreographed cascade of events that has both exogenous (e.g., hypoxia and VEGF) and endogenous regulatory inputs. Not surprisingly, angiogenesis is critical in health and disease. Diverse therapeutics target proteins involved in coordinating angiogenesis with varying degrees of efficacy. It is of great interest that recent work on non-coding RNAs, especially long non-coding RNAs (lncRNAs), indicates that they are also important regulators of the gene expression paradigms that underpin this cellular cascade. The protean effects of lncRNAs are dependent, in part, on their subcellular localization. For instance, lncRNAs enriched in the nucleus can act as epigenetic modifiers of gene expression in the vascular endothelium. Of great interest to genetic disease, they are undergoing rapid evolution and show extensive inter- and intra-species heterogeneity. In this review, we describe endothelial-enriched lncRNAs that have robust effects in angiogenesis.

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Long Non-coding RNAs as Promising Therapeutic Approach in Ischemic Stroke: a Comprehensive Review

Cited by 35 publications

References 99 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

MiR-195-5p Ameliorates Cerebral Ischemia-Reperfusion Injury by Regulating the PTEN-AKT Signaling Pathway

Epigenetic Regulation of the Vascular Endothelium by Angiogenic LncRNAs

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