Circular RNA <i>TLK1</i> Aggravates Neuronal Injury and Neurological Deficits after Ischemic Stroke via miR-335-3p/TIPARP

Wu, Fangfang; Han, Bing; Wu, Shusheng; Yang, Li; Leng, Shuo; Li, Mingyue; Liao, Jiefeng; Wang, Guangtian; Ye, Qingqing; Zhang, Yuan; Chen, Haifeng; Chen, Xufeng; Ming, Zhong; Xu, Yun; Liu, Qiang; Zhang, Junyi; Yao, Honghong

doi:10.1523/jneurosci.0299-19.2019

Cited by 179 publications

(104 citation statements)

References 61 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Our results also support previous findings that circRNAs can serve as novel diagnostic biomarkers and promising therapeutic targets for IS 26,[36][37][38][39] . In the present study, based on the results of bioinformatic analyses, three of the top ten significantly DE circRNAs were selected for PCR validation in AIS patients and healthy controls.…”

Section: Discussionsupporting

confidence: 91%

“…Recent research has shown that the expression of circTLK1 was significantly upregulated in animal brains and circulating blood from animal models of IS and IS patients. Furthermore, knockdown of circTLK1 significantly reduced infarct volumes, decreased ischemic neuronal damage, and improved neurological deficits 13 . Another study manifested that the expression of circRNA HECTD1 was associated with risk, severity and recurrence of AIS 14 .…”

mentioning

confidence: 89%

See 1 more Smart Citation

Expression profile and bioinformatics analysis of circular RNAs in acute ischemic stroke in a South Chinese Han population

Chen

et al. 2020

Sci Rep

View full text Add to dashboard Cite

Recent studies have found that circular RNAs (circRNAs) play crucial roles not only in the normal growth and the development of different tissues and organs but also in the pathogenesis and progression of various disorders. However, the expression patterns and the function of circRNAs in acute ischemic stroke (AIS) in the South Chinese Han population are unclear. In the present study, RNA sequencing (RNA-seq) data was generated from 3 AIS patients and 3 healthy controls. The circRNAs were detected and identified by CIRI2 and Find_circ software. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analyses were used to detect the expression of circRNAs. Meanwhile, the potential diagnostic value of the selected circRNAs for AIS was assessed by generating receiver operating characteristic (ROC) curve with area under curve (AUC). The bioinformatic analysis of the host genes of differentially expressed (DE) circRNAs was performed by gene ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, KOBAS for pathway analysis and regulatory network analysis. miRNA-circRNA and miRNA-mRNA interactions were predicted by using TargetScan, miRanda and starBase. CircRNA-miRNA-mRNA interaction networks were created with Cytoscape. Our result showed that there were 2270 DE circRNAs between AIS patients and healthy controls. Among them, 659 were found upregulated and 1611 were downregulated. Bioinformatic analysis showed that the DE circRNAs were related to the following biological processes: endocytosis, energy metabolism, apoptosis, FoxO signaling pathway, platelet activation, neurotrophin signaling pathway and VEGF signaling pathway, which may be associated with the pathological of AIS. Three randomly selected circRNAs were successfully validated by qRT-PCR. The results show that hsa_circ_0005548 was significantly upregulated, while hsa_circ_0000607 and hsa_circ_0002465 were significantly downregulated in AIS. Furthermore, the AUC values for hsa_circ_005548, hsa_circ_0000607 and hsa_circ_0002465 were 0.51, 0.75 and 0.69, respectively, suggesting that hsa_circ_0000607 and hsa_circ_0002465 could be potential biomarkers for AIS. In addition, Bcl2 was predicted to be a direct target of miR-337-3p, and hsa_circRNA_0000607 was predicted to act as a sponge for miR-337-3p. Thus, hsa_circ_0000607 may be involved in AIS by regulating the miR-337-3p/ Bcl2 axis. Collectively, our findings indicate that numerous dysregulated circRNAs may play pivotal functional roles in AIS and hsa_circ_0000607 may play a crucial role in the pathogenesis and progression of AIS by regulating the miR-337-3p/Bcl2 axis. Stroke is one of the leading causes of death and a major cause of long-term disability worldwide. Approximately 87% of all stroke cases are ischemic stroke (IS) 1. Although major progress in the diagnosis and treatment of acute ischemic stroke (AIS) has been reported in recent years, the mortality and long-term disability rates of IS are still high. Moreover, recombinant tissue plasminogen activa...

show abstract

Section: Discussionsupporting

confidence: 91%

mentioning

confidence: 89%

Expression profile and bioinformatics analysis of circular RNAs in acute ischemic stroke in a South Chinese Han population

Chen

et al. 2020

Sci Rep

View full text Add to dashboard Cite

show abstract

“…As shown in our previous studies, circular RNA SHOC2 (circSHOC2) ameliorates ischemic damage by regulating the autophagy of neurons. 19 In the present study, the circRNA circUCK2 was upregulated during the acute period after focal ischemia. circUCK2 is expressed in neurons, but its function remains unclear.…”

Section: Introductionmentioning

confidence: 99%

RETRACTED: Overexpression of circRNA circUCK2 Attenuates Cell Apoptosis in Cerebral Ischemia-Reperfusion Injury via miR-125b-5p/GDF11 Signaling

Chen

Wang

Feng

et al. 2020

Molecular Therapy - Nucleic Acids

View full text Add to dashboard Cite

Circular RNAs (circRNAs) are expressed at high levels in the brain and are involved in various central nervous system diseases. However, the potential role of circRNAs in ischemic stroke-associated neuronal injury remains largely unknown. Herein, we uncovered the function and underlying mechanism of the circRNA UCK2 (circUCK2) in ischemia stroke. The oxygen-glucose deprivation model in HT-22 cells was used to mimic ischemia stroke in vitro . Neuronal viability and apoptosis were determined by Cell Counting Kit-8 (CCK-8) assays and TUNEL (terminal deoxynucleotidyltransferase-mediated deoxyuridine triphosphate nick end labeling) staining, respectively. Middle cerebral artery occlusion was conducted to evaluate the function of circUCK2 in mice. The levels of circUCK2 were significantly decreased in brain tissues from a mouse model of focal cerebral ischemia and reperfusion. Upregulated circUCK2 levels significantly decreased infarct volumes, attenuated neuronal injury, and improved neurological deficits. circUCK2 reduced oxygen glucose deprivation (OGD)-induced cell apoptosis by regulating transforming growth factor β (TGF-β)/mothers against decapentaplegic homolog 3 (Smad3) signaling. Furthermore, circUCK2 functioned as an endogenous miR-125b-5p sponge to inhibit miR-125b-5p activity, resulting in an increase in growth differentiation factor 11 (GDF11) expression and a subsequent amelioration of neuronal injury. Consequently, these findings showed that the circUCK2/miR-125b-5p/GDF11 axis is an essential signaling pathway during ischemia stroke. Thus, the circRNA circUCK2 may serve as a potential target for novel treatment in patients with ischemic stroke.

show abstract

“…It was increased in the mouse brain after tMCAO and knocking down circRNA TLK1 improve neurological deficits and infarct volume in this stroke mouse model. Remarkably, circRNA TLK1 was observed to be also elevated in human patients after ischemic stroke [38].…”

Section: Discussionmentioning

confidence: 99%

Circular RNA expression profile in blood according to ischemic stroke etiology

et al. 2020

View full text Add to dashboard Cite

Background: The discovery of novel biomarkers of stroke etiology would be most helpful in management of acute ischemic stroke patients. Recently, circular RNAs (circRNAs) have been proposed as candidate biomarkers of neurological conditions due to its high stability. circRNAs function as sponges, sequestering miRNAs and are involved in most relevant biological functions. Our aim was to identify differentially expressed circRNAs in acute ischemic stroke patients according to stroke etiology. Methods: A comprehensive expression profile of blood circRNAs was conducted by Arraystar Human circRNA arrays (13,617 probes) on a discovery cohort of 30 stroke patients with different stroke etiologies by TOAST classification. Real-time quantitative PCR (RT-qPCR) was used to validate array results in a cohort of 50 stroke patients. Functional in silico analysis was performed to identify potential interactions with microRNAs (miRNAs) and pathways underlying deregulated circRNAs. Results: A set of 60 circRNAs were found to be upregulated in atherotrombotic versus cardioembolic strokes (foldchange > = 1.5 and p-value ≤ 0.05). Differential expression of hsa_circRNA_102488, originated from UBA52 gene, was replicated in the validation cohort. RNA-binding proteins (RBPs) sites of hsa_circRNA_102488 clustered around AGO2 and FUS proteins. Further functional analysis revealed interactions between deregulated circRNAs and a set of miRNAs involved in stroke-related pathways, such as fatty acid biogenesis or lysine degradation. Conclusion: Different stroke subtypes show specific profiles of circRNAs expression. circRNAs may serve as a new source of biomarkers of stroke etiology in acute ischemic stroke patients.

show abstract

Circular RNA TLK1 Aggravates Neuronal Injury and Neurological Deficits after Ischemic Stroke via miR-335-3p/TIPARP

Cited by 179 publications

References 61 publications

Expression profile and bioinformatics analysis of circular RNAs in acute ischemic stroke in a South Chinese Han population

Expression profile and bioinformatics analysis of circular RNAs in acute ischemic stroke in a South Chinese Han population

RETRACTED: Overexpression of circRNA circUCK2 Attenuates Cell Apoptosis in Cerebral Ischemia-Reperfusion Injury via miR-125b-5p/GDF11 Signaling

Circular RNA expression profile in blood according to ischemic stroke etiology

Contact Info

Product

Resources

About