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

Frontiers in Immunology, Год журнала: 2022, Номер 13

Опубликована: Окт. 7, 2022

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

Язык: Английский

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Click chemistry extracellular vesicle/peptide/chemokine nanocarriers for treating central nervous system injuries

Acta Pharmaceutica Sinica B, Год журнала: 2022, Номер 13(5), С. 2202 - 2218

Опубликована: Июнь 10, 2022

Central nervous system (CNS) injuries, including stroke, traumatic brain injury, and spinal cord are essential causes of death long-term disability difficult to cure, mainly due the limited neuron regeneration glial scar formation. Herein, we apply extracellular vesicles (EVs) secreted by M2 microglia improve differentiation neural stem cells (NSCs) at injured site, simultaneously modify them with vascular targeting peptide (DA7R) cell recruiting factor (SDF-1) on their surface via copper-free click chemistry recruit NSCs, inducing neuronal differentiation, serving as nanocarriers site (Dual-EV). Results prove that Dual-EV could target human umbilical endothelial (HUVECs), promote NSCs in vitro. Furthermore, 10 miRNAs found be upregulated Dual-M2-EVs compared Dual-M0-EVs bioinformatic analysis, further NSC experiment flow cytometry reveals among these miRNAs, miR30b-3p, miR-222-3p, miR-129-5p, miR-155-5p may exert effect differentiate into neurons. In vivo experiments show achieve improved accumulation ischemic area stroke model mice, potentiate recruitment, increase neurogenesis. This work provides new insights for treatment after CNS injuries well endogenous cells, EV/peptide/chemokine related improving health.

Язык: Английский

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LncRNA XIST regulates breast cancer stem cells by activating proinflammatory IL-6/STAT3 signaling

Oncogene, Год журнала: 2023, Номер 42(18), С. 1419 - 1437

Опубликована: Март 15, 2023

Abstract Aberrant expression of XIST, a long noncoding RNA (lncRNA) initiating X chromosome inactivation (XCI) in early embryogenesis, is common feature breast cancer (BC). However, the roles post-XCI XIST carcinogenesis remain elusive. Here we identify as key regulator stem cells (CSCs), which exhibit aldehyde dehydrogenase positive (ALDH + ) epithelial- (E) and CD24 lo CD44 hi mesenchymal-like (M) phenotypes. variably expressed across spectrum BC subtypes, doxycycline (DOX)-inducible knockdown (KD) markedly inhibits spheroid/colony forming capacity, tumor growth tumor-initiating potential. This phenotype attributed to impaired E-CSC luminal E- M-CSC activities triple-negative (TN) BC. Gene profiling unveils that KD most significantly affects cytokine-cytokine receptor interactions, leading suppressed proinflammatory cytokines IL-6 IL-8 ALDH - bulk cells. Exogenous IL-6, but not IL-8, rescues reduced sphere-forming capacity proportion E-CSCs TN upon KD. functions nuclear sponge for microRNA let-7a-2-3p activate production from cells, acts paracrine fashion on display elevated cell surface (IL6R) expression. promotes CSC self-renewal via STAT3 activation factors including c-MYC, KLF4 SOX9. Together, this study supports novel role by derepressing let-7 controlled signaling promote self-renewal.

Язык: Английский

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Rho/ROCK Pathway and Noncoding RNAs: Implications in Ischemic Stroke and Spinal Cord Injury

International Journal of Molecular Sciences, Год журнала: 2021, Номер 22(21), С. 11573 - 11573

Опубликована: Окт. 26, 2021

Ischemic strokes (IS) and spinal cord injuries (SCI) are major causes of disability. RhoA is a small GTPase protein that activates downstream effector, ROCK. The up-regulation the RhoA/ROCK pathway contributes to neuronal apoptosis, neuroinflammation, blood-brain barrier dysfunction, astrogliosis, axon growth inhibition in IS SCI. Noncoding RNAs (ncRNAs), such as microRNAs (miRNAs) long noncoding (lncRNAs), were previously considered be non-functional. However, they have attracted much attention because play an essential role regulating gene expression physiological pathological conditions. There growing evidence ROCK inhibitors, fasudil VX-210, can reduce injury SCI animal models clinical trials. Recently, it has been reported miRNAs decreased SCI, while lncRNAs increased. Inhibiting Rho/ROCK with alleviates oxidative stress, Further studies required explore significance ncRNAs establish new strategies for preventing treating these devastating diseases.

Язык: Английский

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Identification of programmed cell death-related gene signature and associated regulatory axis in cerebral ischemia/reperfusion injury

Frontiers in Genetics, Год журнала: 2022, Номер 13

Опубликована: Авг. 4, 2022

Background: Numerous studies have suggested that programmed cell death (PCD) pathways play vital roles in cerebral ischemia/reperfusion (I/R) injury. However, the specific mechanisms underlying during I/R injury yet to be completely clarified. There is thus a need identify PCD-related gene signatures and associated regulatory axes injury, which should provide novel therapeutic targets against Methods: We analyzed transcriptome of brain tissue samples from mice subjected middle artery occlusion/reperfusion (MCAO/R) matched controls, identified differentially expressed genes related three types PCD(apoptosis, pyroptosis, necroptosis). next performed functional enrichment analysis constructed competing endogenous RNA (ceRNA) networks. also conducted hub nodes key axes. Results: Fifteen were identified. Functional showed they particularly with corresponding biological processes, inflammatory response, reactive oxygen species metabolic processes. The apoptosis-related ceRNA network was constructed, included 24 long noncoding RNAs (lncRNAs), 41 microRNAs (miRNAs), 4 messenger (mRNAs); necroptosis-related 16 lncRNAs, 20 miRNAs, 6 mRNAs; pyroptosis-related 15 18 mRNAs. Hub each seven total, namely, lncRNA Malat1/miR-181a-5p/Mapt, Malat1/miR-181b-5p/Mapt, Neat1/miR-181a-5p/Mapt, Neat1/miR-181b-5p/Mapt for network; Neat1/miR-181a-5p/Tnf Malat1/miR-181c-5p/Tnf lncRNAMalat1/miR-181a-5p both Conclusion: results this study supported hypothesis these PCD (apoptosis, necroptosis, PANoptosis) crosstalk among them might involved ischemic stroke regulating above This may offer new insights into potential neuroprotection.

Язык: Английский

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Emodin Regulates lncRNA XIST/miR-217 Axis to Protect Myocardial Ischemia-Reperfusion Injury

Oxidative Medicine and Cellular Longevity, Год журнала: 2023, Номер 2023, С. 1 - 9

Опубликована: Янв. 31, 2023

This study is aimed at investigating the effect of emodin on myocardial ischemia-reperfusion injury (MIRI) and mechanism.Eighty healthy adult male SD rats (weighing 230-250 g) were utilized to establish I/R model, which randomly divided into five groups (16 in each group): sham operation group, group (I/R group), +NC +XIST group. The contents CK, CK-MB, LDH, HBDH serum determined by ELISA kit. LDH was detected assay, SOD xanthine oxidase method, MDA thiobarbituric acid method. relative expression XIST miR-217 evaluated RT-qPCR. Western blot applied detect protein expression. Flow cytometry cardiomyocyte apoptosis.Myocardial infarction area obviously increased model rats, while decreased rats. In addition, cardiac enzymes (CK, HBDH) apoptosis MIRI apoptosis. ROS levels raised activities declined markedly overexpression reversed protective infarction, oxidative stress, directly regulated miR-217, si-XIST inhibited H/R-induced damage cardiomyocytes via inhibiting miR-217.Emodin protected both vitro vivo lncRNA upregulate miR-217.

Язык: Английский

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Emerging Role of LncRNAs in Ischemic Stroke—Novel Insights into the Regulation of Inflammation

Journal of Inflammation Research, Год журнала: 2021, Номер Volume 14, С. 4467 - 4483

Опубликована: Сен. 1, 2021

Abstract: As a crucial kind of pervasive gene, long noncoding RNAs (lncRNAs) are abundant and key players in brain function as well numerous neurological disorders, especially ischemic stroke. The mechanisms underlying stroke include angiogenesis, autophagy, apoptosis, cell death, neuroinflammation. Inflammation plays vital role the pathological process stroke, systemic inflammation affects patient's prognosis. Although great deal research has illustrated that various lncRNAs closely relevant to regulate neuroinflammation microglial activation specific interactional relationships between have not been described clearly. This review aimed summarize therapeutic effects action on ischemia by regulating activation. In addition, we emphasize potential modulate inhibiting activating signaling pathways, such microRNAs, NF‐κB ERK. Keywords: RNA, microglia,

Язык: Английский

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Integrated Bioinformatics and Validation of lncRNA-Mediated ceRNA Network in Myocardial Ischemia/Reperfusion Injury

Journal of Immunology Research, Год журнала: 2022, Номер 2022, С. 1 - 13

Опубликована: Сен. 21, 2022

Background. Myocardial ischemia/reperfusion (MI/R) injury is a common pathology in ischemia heart disease. Long noncoding RNAs (lncRNAs) are significant regulators related to many conditions. This study aimed at exploring the molecule mechanism of lncRNA-mediated competing endogenous RNA (ceRNA) network MI/R. Methods. The dataset profiles MI/R and normal tissues (GSE130217 GSE124176) were obtained from GEO database. Integrated bioinformatics performed screen out differentially expressed genes (DEGs). Thereafter, an ceRNA was constructed by starBase GO annotations KEGG pathway analysis conducted action pathways DEGs A model hypoxia/reoxygenation- (H/R-) treated HL-1 cell verify expression lncRNAs through qRT-PCR. Results. 2406 expressed- (DE-) mRNAs, 70 DE-lncRNAs, 156 DE-miRNAs acquired. These construct network, subnetwork including lncRNA Xist/miRNA-133c/mRNA (Slc30a9) out. functional enrichment analyses revealed that involved might functions oxidative stress calcium signaling pathway. Xist reduced under H/R conditions, followed increased level miRNA-133c, thus downregulating Slc30a9. Conclusion. In sum, identified which included Xist/miR-133c/Slc30a9 axis contribute better understanding pathogenesis development offer novel targeted therapy way.

Язык: Английский

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XIST in Brain Cancer

Clinica Chimica Acta, Год журнала: 2022, Номер 531, С. 283 - 290

Опубликована: Апрель 26, 2022

Язык: Английский

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CircUSP39/miR-362-3p/TRAF3 Axis Mediates Hypoxia/Reoxygenation-Induced Cardiomyocyte Oxidative Stress, Inflammation, and Apoptosis

International Heart Journal, Год журнала: 2023, Номер 64(2), С. 263 - 273

Опубликована: Март 30, 2023

Accumulating evidence suggested that aberrantly regulated circular RNA (circRNA) is a critical contributor to cardiovascular diseases, including acute myocardial infarction (AMI). However, the role and molecular mechanism of circUSP39 in AMI development remain unclear.Candidate circRNAs were screened from Gene Expression Omnibus (GEO) database (GSE160717) analyzed using GEO2R tool. Hypoxia/reoxygenation (H/R) -induced AC16 cells used investigate function H/R injury cardiomyocytes. Quantitative real-time PCR (qRT-PCR) was employed test levels H/R-induced cells. Cell Counting Kit-8, enzyme-linked immunosorbent assay, flow cytometry, western blot (WB) assay determine cell viability, oxidative stress, inflammatory factor levels, apoptosis. immunoprecipitation, pull-down, dual-luciferase reporter conducted validate interactions between circRNA ubiquitin-specific peptidase 39 (circUSP39), miR-362-3p, tumor necrosis receptor-associated 3 (TRAF3).In cells, expression TRAF3 upregulated whereas miR-362-3p downregulated. CircUSP39 silencing markedly enhanced viability superoxide dismutase activity but mitigated malondialdehyde level, secretion factors (IL-6, TNF-α, IL-1β, MCP-1), apoptosis expedited by sponging increase TRAF3.CircUSP39 could facilitate cardiomyocyte inflammation, miR-362-3p/TRAF3 axis, elucidating it might be therapeutic target for AMI.

Язык: Английский

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