Altered circular RNA expression profiles in the non-ischemic thalamus in focal cortical infarction mice

Li, Fangming; Li, Chuqiao; Li, Xiaoqiang; Li, Yudi; Zhong, Yulan; Li, Ling

doi:10.18632/aging.103424

Cited by 21 publications

(12 citation statements)

References 39 publications

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“…CircRNAs, which are made up of introns or exons and formed through gene rearrangement or non-linear mode of RNA splicing, are widely present in the human cell [ 18 , 19 ]. They are more stable and more conserved compared with the other noncoding RNAs, which lead to potentially be used as new diagnostic molecular biological markers and therapeutic targets [ 20 , 21 ]. Recently, many studies had shown that circRNAs exert the regulation functions in multiple diseases, such as cardiovascular disease [ 22 ], lung cancer [ 23 ], Alzheimer’s disease [ 24 ], and neurological disorders [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

Circular RNA circ_0000423 regulates cartilage ECM synthesis via circ_0000423/miRNA-27b-3p/MMP-13 axis in osteoarthritis

Xie

Xiao

et al. 2022

Aging

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Circular RNA (circRNA) is related to many human diseases including osteoarthritis (OA). Our research purpose was to show that functional circRNAs have a role in the pathogenesis of OA, while also identifying potential circRNA that bind to miRNA-27b-3p. Microarray analysis was used to evaluate the expression of CircRNA in OA and normal cartilage. The role and functional mechanism of Circ_0000423 up-regulation were detected in OA and verified in vitro and in vivo . RNA transfection, qRT-PCR, Western blot analysis, immunofluorescence, and dual-luciferase assays were used to investigate the interaction between Circ_0000423 and miRNA-27b-3p in vitro . The roles of Circ_0000423 were discussed in vivo . Our results discovered 11 down-regulated circRNAs and 101 up-regulated circRNAs between control and OA tissues, and confirmed that Circ_0000423 an increase significantly in OA tissues by evaluating the different circRNAs expressions. Meanwhile, luciferase analysis confirmed Circ_0000423 can be directly targeted by miRNA-27b-3p and act as a miRNA-27b-3p sponge. Circ_0000423 can influence MMP-13 and collagen II expression by targeting miRNA-27b-3p expression as ceRNA in OA. Furthermore, AAV-shRNA-Circ 0000423 intra-articular injection slows the progression of OA by decreasing articular cartilage destruction and erosion, joint surface fibrosis, osteophyte formation, MMP-13 expression, and increasing collagen II expression in the articular cartilage of ACLT-induced OA mice model. These findings confirmed that the Circ_0000423-miRNA-27b-3p-MMP-13 axis could affect the pathogenesis of OA which might lead to a novel target for diagnostic molecular biological indicators and potential OA treatments.

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Section: Discussionmentioning

confidence: 99%

Circular RNA circ_0000423 regulates cartilage ECM synthesis via circ_0000423/miRNA-27b-3p/MMP-13 axis in osteoarthritis

Xie

Xiao

et al. 2022

Aging

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“…Duan and coworkers conducted high-throughput sequencing of whole-brain tissues on the infarcted side 4 days after MCAO in rats [ 47 ]. Li et al [ 48 ] analyzed circRNAs in thalamic tissues on the infarcted side 7 and 14 days after focal cerebral infarction in mice, and the Mehta group used microarrays to detect changes in whole-brain circRNA expression patterns at 6, 12, and 24 h after post-MCAO reperfusion in mice [ 49 ]. Wouters and colleagues demonstrated a clear correlation between stroke severity in the early stages, especially at 24 h of onset, and stroke recovery [ 50 ], and they validated the importance of early stroke injury changes and interventions for stroke management [ 51 ].…”

Section: Discussionmentioning

confidence: 99%

Deep Sequencing of the Rat MCAO Cortexes Reveals Crucial circRNAs Involved in Early Stroke Events and Their Regulatory Networks

Wang

Yang

et al. 2021

Neural Plasticity

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Circular RNAs (circRNAs) are highly enriched in the central nervous system and significantly involved in a range of brain-related physiological and pathological processes. Ischemic stroke is a complex disorder caused by multiple factors; however, whether brain-derived circRNAs participate in the complex regulatory networks involved in stroke pathogenesis remains unknown. Here, we successfully constructed a cerebral ischemia-injury model of middle cerebral artery occlusion (MCAO) in male Sprague-Dawley rats. Preliminary qualitative and quantitative analyses of poststroke cortical circRNAs were performed through deep sequencing, and RT-PCR and qRT-PCR were used for validation. Of the 24,858 circRNAs expressed in the rat cerebral cortex, 294 circRNAs were differentially expressed in the ipsilateral cerebral cortex between the MCAO and sham rat groups. Cluster, GO, and KEGG analyses showed enrichments of these circRNAs and their host genes in numerous biological processes and pathways closely related to stroke. We selected 106 of the 294 circRNAs and constructed a circRNA-miRNA-mRNA interaction network comprising 577 sponge miRNAs and 696 target mRNAs. In total, 15 key potential circRNAs were predicted to be involved in the posttranscriptional regulation of a series of downstream target genes, which are widely implicated in poststroke processes, such as oxidative stress, apoptosis, inflammatory response, and nerve regeneration, through the competing endogenous RNA mechanism. Thus, circRNAs appear to be involved in multilevel actions that regulate the vast network of multiple mechanisms and events that occur after a stroke. These results provide novel insights into the complex pathophysiological mechanisms of stroke.

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“…Finally, it was found that circBBS2 and circPHKA2 were differentially expressed in the blood of AIS patients. Li et al found that a total of 2 659 circRNAs were significantly altered in the ipsilateral thalamus of adult male C57BL/6J mice in the permanent distal MCAO model compared with the sham-operated group (154). Among them, 73 circRNAs were significantly changed at 2 time points after modeling (154).…”

Section: Mehta Et Al Established a Tmcao Model In Male C57bl6jmentioning

confidence: 99%

“…Li et al found that a total of 2 659 circRNAs were significantly altered in the ipsilateral thalamus of adult male C57BL/6J mice in the permanent distal MCAO model compared with the sham-operated group (154). Among them, 73 circRNAs were significantly changed at 2 time points after modeling (154). GO and KEGG analysis showed that circRNAs play an important role in secondary thalamic neurodegeneration and remodeling after focal cortical infarction, suggesting that circRNAs may be therapeutic targets to alleviate secondary distal neurodegeneration after stroke.…”

Section: Mehta Et Al Established a Tmcao Model In Male C57bl6jmentioning

confidence: 99%

A systematic review of the research progress of non-coding RNA in neuroinflammation and immune regulation in cerebral infarction/ischemia-reperfusion injury

Yang

Zeng

et al. 2022

Front. Immunol.

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Cerebral infarction/ischemia-reperfusion injury is currently the disease with the highest mortality and disability rate of cardiovascular disease. Current studies have shown that nerve cells die of ischemia several hours after ischemic stroke, which activates the innate immune response in the brain, promotes the production of neurotoxic substances such as inflammatory cytokines, chemokines, reactive oxygen species and − nitrogen oxide, and mediates the destruction of blood-brain barrier and the occurrence of a series of inflammatory cascade reactions. Meanwhile, the expression of adhesion molecules in cerebral vascular endothelial cells increased, and immune inflammatory cells such as polymorphonuclear neutrophils, lymphocytes and mononuclear macrophages passed through vascular endothelial cells and entered the brain tissue. These cells recognize antigens exposed by the central nervous system in the brain, activate adaptive immune responses, and further mediate secondary neuronal damage, aggravating neurological deficits. In order to reduce the above-mentioned damage, the body induces peripheral immunosuppressive responses through negative feedback, which increases the incidence of post-stroke infection. This process is accompanied by changes in the immune status of the ischemic brain tissue in local and systemic systems. A growing number of studies implicate noncoding RNAs (ncRNAs) as novel epigenetic regulatory elements in the dysfunction of various cell subsets in the neurovascular unit after cerebral infarction/ischemia-reperfusion injury. In particular, recent studies have revealed advances in ncRNA biology that greatly expand the understanding of epigenetic regulation of immune responses and inflammation after cerebral infarction/ischemia-reperfusion injury. Identification of aberrant expression patterns and associated biological effects of ncRNAs in patients revealed their potential as novel biomarkers and therapeutic targets for cerebral infarction/ischemia-reperfusion injury. Therefore, this review systematically presents recent studies on the involvement of ncRNAs in cerebral infarction/ischemia-reperfusion injury and neuroimmune inflammatory cascades, and elucidates the functions and mechanisms of cerebral infarction/ischemia-reperfusion-related ncRNAs, providing new opportunities for the discovery of disease biomarkers and targeted therapy. Furthermore, this review introduces clustered regularly interspaced short palindromic repeats (CRISPR)-Display as a possible transformative tool for studying lncRNAs. In the future, ncRNA is expected to be used as a target for diagnosing cerebral infarction/ischemia-reperfusion injury, judging its prognosis and treatment, thereby significantly improving the prognosis of patients.

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Altered circular RNA expression profiles in the non-ischemic thalamus in focal cortical infarction mice

Cited by 21 publications

References 39 publications

Circular RNA circ_0000423 regulates cartilage ECM synthesis via circ_0000423/miRNA-27b-3p/MMP-13 axis in osteoarthritis

Circular RNA circ_0000423 regulates cartilage ECM synthesis via circ_0000423/miRNA-27b-3p/MMP-13 axis in osteoarthritis

Deep Sequencing of the Rat MCAO Cortexes Reveals Crucial circRNAs Involved in Early Stroke Events and Their Regulatory Networks

A systematic review of the research progress of non-coding RNA in neuroinflammation and immune regulation in cerebral infarction/ischemia-reperfusion injury

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