circGNAQ, a circular RNA enriched in vascular endothelium, inhibits endothelial cell senescence and atherosclerosis progression

Wu, Weipeng; Zhou, Meng-Yuan; Liu, Dongliang; Xue, Mei; Shao, Tong; Xu, Ziyang; Xia, Jing; Cai, Meiying; Xu, Shun; Liang, Xin; Mo, Miaohua; Liu, Xinguang; Xiong, Xing‐Dong

doi:10.1016/j.omtn.2021.07.020

Cited by 38 publications

(23 citation statements)

References 53 publications

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“…48 Studies have shown that the expression of astrocyte lamina is significantly increased in the ischemic penumbra of MCAO mice. 49 COL4A is a member of type IV collagen family 50 and the most abundant basal lamina protein, 48 which participates in modulating cellular behaviors during the processes of tissue development, damage, and repair. For example, COL4A1 is considered as a monogenic cause of cerebral small vessel disease, including both ischemic stroke and intracerebral hemorrhage.…”

Section: Discussionmentioning

confidence: 99%

CircOGDH Is a Penumbra Biomarker and Therapeutic Target in Acute Ischemic Stroke

Liu

Zang

et al. 2022

Circulation Research

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Background: Acute ischemic stroke (AIS) is a leading cause of disability and mortality worldwide. Prediction of penumbra existence after AIS is crucial for making decision on reperfusion therapy. Yet a fast, inexpensive, simple, and noninvasive predictive biomarker for the poststroke penumbra with clinical translational potential is still lacking. We aim to investigate whether the CircOGDH (circular RNA derived from oxoglutarate dehydrogenase) is a potential biomarker for penumbra in patients with AIS and its role in ischemic neuronal damage. Methods: CircOGDH was screened from penumbra of middle cerebral artery occlusion mice and was assessed in plasma of patients with AIS by quantitative polymerase chain reaction. Magnetic resonance imaging was used to examine the penumbra volumes. CircOGDH interacted with miR-5112 in primary cortical neurons was detected by fluorescence in situ hybridization, RNA immunoprecipitation, and luciferase reporter assay. ADV-mediated CircOGDH knockdown ameliorated neuronal apoptosis induced by COL4A4 (Gallus collagen, type VI, alpha VI) overexpression. Transmission electron microscope, nanoparticle tracking analysis, and Western blot were performed to confirm exosomes. Results: CircOGDH expression was dramatically and selectively upregulated in the penumbra tissue of middle cerebral artery occlusion mice and in the plasma of 45 patients with AIS showing a 54-fold enhancement versus noncerebrovascular disease controls. Partial regression analysis revealed that CircOGDH expression was positively correlated with the size of penumbra in patients with AIS. Sequestering of miR-5112 by CircOGDH enhanced COL4A4 expression to elevate neuron damage. Additionally, knockdown of CircOGDH significantly enhanced neuronal cell viability under ischemic conditions. Furthermore, the expression of CircOGDH in brain tissue was closely related to that in the serum of middle cerebral artery occlusion mice. Finally, we found that CircOGDH was highly expressed in plasma exosomes of patients with AIS compared with those in noncerebrovascular disease individuals. Conclusions: These results demonstrate that CircOGDH is a potential therapeutic target for regulating ischemia neuronal viability, and is enriched in neuron-derived exosomes in the peripheral blood, exhibiting a predictive biomarker of penumbra in patients with AIS.

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Section: Discussionmentioning

confidence: 99%

CircOGDH Is a Penumbra Biomarker and Therapeutic Target in Acute Ischemic Stroke

Liu

Zang

et al. 2022

Circulation Research

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“…The circular RNA circ_0003204 inhibits the proliferation, migration and tube formation of endothelial cells in atherosclerosis via the miR-370-3p/TGFβR2/phosph-SMAD3 axis [ 21 ]. circGNAQ was reported to inhibit endothelial cell senescence and atherosclerosis progression [ 22 ].However, the potential mechanism of circRNA on endothelium cells was rarely studied.…”

Section: Discussionmentioning

confidence: 99%

Hsa_circ_0001879 promotes the progression of atherosclerosis by regulating the proliferation and migration of oxidation of low density lipoprotein (ox-LDL)-induced vascular endothelial cells via the miR-6873-5p-HDAC9 axis

Chen

et al. 2021

Bioengineered

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Atherosclerosis (AS) is a typical vascular disease. Emerging evidence has shown that circRNAs play key roles in the progression of AS, but the potential function and underlying mechanism of hsa_circ_0001879 remains unknown. We detected the expression level of hsa_circ_0001879 was determined by qRT-PCR, and the proliferation rate and migration ability of HUVECs were measured by CCK-8 assay and Transwell assay, respectively. Proliferative markers and epithelium mesenchymal transition (EMT) markers were measured through immunoblotting. A dual luciferase activity assay was performed to detect the interaction between circRNAs, miRNAs, and mRNAs. Hsa_circ_0001879 was upregulated in AS patients. Hsa_circ_0001879 inhibited the proliferation and migration ability of Human umbilical vein endothelial cells (HUVECs). Hsa_circ_0001879 directly bound to miR-6873-5p and acted as a sponge. miR-6873-5p-induced HDAC9 mRNA degradation was inhibited by hsa_circ_0001879. Hsa_circ_0001879 decreased the proliferation and migration of HUVECs by inhibiting miR-6873-5p-induced HDAC9 degradation.

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“…circGNAQ. Very recently, Wu et al correlated circGNAQ to the senescence of endothelial cells [288]. The levels of circGNAQ were reduced in senescent endothelial cells, as well as in aorta tissues from aged mice and in human blood samples from old people.…”

Section: Circular Rnas (Circrnas)mentioning

confidence: 99%

“…Further analyses demonstrated that circGNAQ sponges miR-146a-5p, which functionally affects the expression of polo-like kinase2 (PLK2), an enzyme implicated in cell cycle progression. Of interest, mice injected with circGNAQ showed reduced signs of atherosclerosis after the high fat diet [288].…”

Section: Circular Rnas (Circrnas)mentioning

confidence: 99%

MicroRNAs, Long Non-Coding RNAs, and Circular RNAs in the Redox Control of Cell Senescence

et al. 2022

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Cell senescence is critical in diverse aspects of organism life. It is involved in tissue development and homeostasis, as well as in tumor suppression. Consequently, it is tightly integrated with basic physiological processes during life. On the other hand, senescence is gradually being considered as a major contributor of organismal aging and age-related diseases. Increased oxidative stress is one of the main risk factors for cellular damages, and thus a driver of senescence. In fact, there is an intimate link between cell senescence and response to different types of cellular stress. Oxidative stress occurs when the production of reactive oxygen species/reactive nitrogen species (ROS/RNS) is not adequately detoxified by the antioxidant defense systems. Non-coding RNAs are endogenous transcripts that govern gene regulatory networks, thus impacting both physiological and pathological events. Among these molecules, microRNAs, long non-coding RNAs, and more recently circular RNAs are considered crucial mediators of almost all cellular processes, including those implicated in oxidative stress responses. Here, we will describe recent data on the link between ROS/RNS-induced senescence and the current knowledge on the role of non-coding RNAs in the senescence program.

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circGNAQ, a circular RNA enriched in vascular endothelium, inhibits endothelial cell senescence and atherosclerosis progression

Cited by 38 publications

References 53 publications

CircOGDH Is a Penumbra Biomarker and Therapeutic Target in Acute Ischemic Stroke

CircOGDH Is a Penumbra Biomarker and Therapeutic Target in Acute Ischemic Stroke

Hsa_circ_0001879 promotes the progression of atherosclerosis by regulating the proliferation and migration of oxidation of low density lipoprotein (ox-LDL)-induced vascular endothelial cells via the miR-6873-5p-HDAC9 axis

MicroRNAs, Long Non-Coding RNAs, and Circular RNAs in the Redox Control of Cell Senescence

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