Circular RNA circ-FoxO3 attenuates blood-brain barrier damage by inducing autophagy during ischemia/reperfusion

Yang, Zhen-Guo; Huang, Cheng; Wen, Xueyi; Liu, Wenlin; Huang, Xiao-Xiong; Li, Yufeng; Zang, Jiankun; Weng, Zean; Lu, Dan; Tsang, Chi Kwan; Li, Keshen; Xu, Anding

doi:10.1016/j.ymthe.2021.11.004

Cited by 72 publications

(56 citation statements)

References 49 publications

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“…Upregulation of circ-FoxO3 and autophagic flux were detected in brain microvessel endothelial cells in patients with hemorrhagic transformation and in mice models with middle cerebral artery occlusion/reperfusion. In vivo and in vitro studies indicated that circ-FoxO3 alleviated BBB damage principally by autophagy activation via mTORC1 inhibition (Yang et al, 2022 ). These findings suggest that non-coding RNA may have important regulatory potential in the occurrence of hemorrhagic transformation after stroke.…”

Section: Introductionmentioning

confidence: 99%

Differential Expression and Correlation Analysis of Global Transcriptome for Hemorrhagic Transformation After Acute Ischemic Stroke

Han

Zhang

et al. 2022

Front. Neurosci.

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In order to explore the epigenetic characteristics of hemorrhagic transformation (HT) after acute ischemic stroke, we used transcriptome sequencing technology to analyze the global transcriptome expression profile of patients with and without HT after acute ischemic stroke and to study the differential expression of messenger RNA (mRNA), long noncoding RNA (lncRNA), circular RNA (circRNA) and mircoRNA (miRNA) between the two groups. To further explore the role of differentially expressed genes in HT, we annotated the function of differentially expressed genes by using gene ontology (GO) and pathway analysis on the results and showed that there were 1,051 differential expressions of lncRNAs, 2,575 differential expressions of mRNAs, 447 differential expressions of circRNAs and 47 miRNAs in patients with HT compared with non-HT patients. Pathway analysis showed that ubiquitin-mediated proteolysis, MAPK signal pathway, axon guidance, HIF-1 signal pathway, NOD-like receptor signal pathway, beta-alanine metabolism, Wnt signal pathway, sphingolipid signal pathway, neuroactive ligand-receptor interaction, and intestinal immune network used in IgA production play an important role in HT. Terms such as iron homeostasis, defense response, immune system process, DNA conformational change, production of transforming growth factor beta-2, and oxidoreductase activity were enriched in the gene list, suggesting a potential correlation with HT. A total of 261 lncRNA-miRNA relationship pairs and 21 circRNA-miRNA relationship pairs were obtained; additionally, 5 circRNAs and 13 lncRNAs were screened, which can be used as competing endogenous RNA (ceRNA) to compete with miRNA in the co-expression network. Co-expression network analysis shows that these differentially expressed circRNA and lncRNA may play a vital role in HT and provide valuable information for new biomarkers or therapeutic targets.

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Section: Introductionmentioning

confidence: 99%

Differential Expression and Correlation Analysis of Global Transcriptome for Hemorrhagic Transformation After Acute Ischemic Stroke

Han

Zhang

et al. 2022

Front. Neurosci.

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“…In addition, Yu et al showed that Netrin-1, an axonal guidance molecule, enhanced autophagy activity via PI3K pathway depending on UNC5H2 receptor and attenuated BBB impairment induced by ischemic stroke by promoting tight junction function and endothelial survival [ 129 ]. Moreover, recent studies also suggested that endothelial autophagy might contribute to blood-brain barrier protection after ischemic stroke [ 130 , 131 ].…”

Section: Autophagy In Ischemic Strokementioning

confidence: 99%

“… Manipulation of autophagy in brain microvascular endothelial cells after ischemic stroke. Circ-FoxO3 inhibits mTORC1 activity mainly by sequestering mTOR and E2F1, thus promoting autophagy to clear cytotoxic aggregates for improving BBB integrity [ 130 ]. Netrin-1 ameliorates BBB impairment secondary to ischemic stroke by activating PI3K-mediated autophagy depending on UNC5H2 receptor [ 129 ].…”

Section: Figurementioning

confidence: 99%

Novel Therapeutic Strategies for Ischemic Stroke: Recent Insights into Autophagy

Zhang

Ding

et al. 2022

Oxidative Medicine and Cellular Longevity

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Stroke is one of the leading causes of death and disability worldwide. Autophagy is a conserved cellular catabolic pathway that maintains cellular homeostasis by removal of damaged proteins and organelles, which is critical for the maintenance of energy and function homeostasis of cells. Accumulating evidence demonstrates that autophagy plays important roles in pathophysiological mechanisms under ischemic stroke. Previous investigations show that autophagy serves as a “double-edged sword” in ischemic stroke as it can either promote the survival of neuronal cells or induce cell death in special conditions. Following ischemic stroke, autophagy is activated or inhibited in several cell types in brain, including neurons, astrocytes, and microglia, as well as microvascular endothelial cells, which involves in inflammatory activation, modulation of microglial phenotypes, and blood-brain barrier permeability. However, the exact mechanisms of underlying the role of autophagy in ischemic stroke are not fully understood. This review focuses on the recent advances regarding potential molecular mechanisms of autophagy in different cell types. The focus is also on discussing the “double-edged sword” effect of autophagy in ischemic stroke and its possible underlying mechanisms. In addition, potential therapeutic strategies for ischemic stroke targeting autophagy are also reviewed.

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“…Particularly, circFoxo3 expression was increased in adriamycin-resistant hepatocellular carcinoma tissues and cell lines, and its overexpression enhances hepatocellular carcinoma invasion and growth via the miR-199a-5p/ATP Binding Cassette Subfamily C Member 1 (ABCC1) axis [ 126 ]. Moreover, the role of circFoxo3 in cardiac and neurologic diseases has also been well-explored [ 127 , 128 , 129 , 130 ].…”

Section: Circrnas and Drug Resistance In Pcamentioning

confidence: 99%

Circular RNAs and Drug Resistance in Genitourinary Cancers: A Literature Review

Long

Shi

et al. 2022

Cancers

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In recent years, systematic treatment has made great progress in genitourinary tumors. However, some patients develop resistance to the treatments, resulting in an increase in mortality. Circular RNAs (circRNAs) form a class of non-coding RNAs with high stability and significant clinical relevance. Accumulating evidence indicates that circRNAs play a vital role in cancer development and tumor chemotherapy resistance. This review summarizes the molecular and cellular mechanisms of drug resistance mediated by circRNAs to common drugs used in the treatment of genitourinary tumors. Several circRNAs were identified to regulate the responsiveness to systemic treatments in genitourinary tumors, including chemotherapies such as cisplatin and targeted therapies such as enzalutamide. Canonically, cicrRNAs participate in the competing endogenous RNA (ceRNA) network, or in some cases directly interact with proteins, regulate downstream pathways, and even some circRNAs have the potential to produce proteins or polypeptides. Several cellular mechanisms were involved in circRNA-dependent drug resistance, including autophagy, cancer stem cells, epithelial-mesenchymal transition, and exosomes. The potential clinical prospect of circRNAs in regulating tumor drug resistance was also discussed.

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Circular RNA circ-FoxO3 attenuates blood-brain barrier damage by inducing autophagy during ischemia/reperfusion

Cited by 72 publications

References 49 publications

Differential Expression and Correlation Analysis of Global Transcriptome for Hemorrhagic Transformation After Acute Ischemic Stroke

Differential Expression and Correlation Analysis of Global Transcriptome for Hemorrhagic Transformation After Acute Ischemic Stroke

Novel Therapeutic Strategies for Ischemic Stroke: Recent Insights into Autophagy

Circular RNAs and Drug Resistance in Genitourinary Cancers: A Literature Review

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