scholarly journals Long Non-coding RNAs and Circular RNAs: Insights Into Microglia and Astrocyte Mediated Neurological Diseases

2021 ◽  
Vol 14 ◽  
Author(s):  
Miaomiao Chen ◽  
Xingning Lai ◽  
Xifeng Wang ◽  
Jun Ying ◽  
Lieliang Zhang ◽  
...  
Keyword(s):  
Ischemia Reperfusion Injury ◽  
Neurological Diseases ◽  
Ischemia Reperfusion ◽  
Circular Rnas ◽  
Messenger Rnas ◽  
Cord Injury ◽  
Competing Endogenous Rnas ◽  
Inflammatory Phenotype ◽  
Neuron Damage ◽  
Non Coding Rnas

Microglia and astrocytes maintain tissue homeostasis in the nervous system. Both microglia and astrocytes have pro-inflammatory phenotype and anti-inflammatory phenotype. Activated microglia and activated astrocytes can contribute to several neurological diseases. Long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), two groups of non-coding RNAs (ncRNAs), can function as competing endogenous RNAs (ceRNAs) to impair the microRNA (miRNA) inhibition on targeted messenger RNAs (mRNAs). LncRNAs and circRNAs are involved in various neurological disorders. In this review, we summarized that lncRNAs and circRNAs participate in microglia dysfunction, astrocyte dysfunction, neuron damage, and inflammation. Thereby, lncRNAs and circRNAs can positively or negatively regulate neurological diseases, including spinal cord injury (SCI), traumatic brain injury (TBI), ischemia-reperfusion injury (IRI), stroke, neuropathic pain, epilepsy, Parkinson’s disease (PD), multiple sclerosis (MS), and Alzheimer’s disease (AD). Besides, we also found a lncRNA/circRNA-miRNA-mRNA regulatory network in microglia and astrocyte mediated neurological diseases. Through this review, we hope to cast light on the regulatory mechanisms of lncRNAs and circRNAs in microglia and astrocyte mediated neurological diseases and provide new insights for neurological disease treatment.

scholarly journals Non-coding RNAs modulate autophagy in myocardial ischemia-reperfusion injury: a systematic review

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Fuwen Huang ◽  
Jingting Mai ◽  
Jingwei Chen ◽  
Yinying He ◽  
Xiaojun Chen
Keyword(s):  
Myocardial Infarction ◽  
Cardiovascular Diseases ◽  
Myocardial Ischemia ◽  
Molecular Mechanisms ◽  
Ischemia Reperfusion Injury ◽  
Heart Function ◽  
Ischemia Reperfusion ◽  
Circular Rnas ◽  
Non Coding Rnas ◽  
Myocardial Ischemia Reperfusion

AbstractThe myocardial infarction is the main cause of morbidity and mortality in cardiovascular diseases around the world. Although the timely and complete reperfusion via Percutaneous Coronary Intervention (PCI) or thrombolysis have distinctly decreased the mortality of myocardial infarction, reperfusion itself may lead to supererogatory irreversible myocardial injury and heart function disorders, namely ischemia-reperfusion (I/R) injury. Extensive studies have indicated that non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs), play important roles in the progress of myocardial I/R injury, which is closely correlative with cardiomyocytes autophagy. Moreover, autophagy plays an important role in maintaining homeostasis and protecting cells in the myocardial ischemia reperfusion and cardiomyocyte hypoxia-reoxygenation (H/R) progress. In this review, we first introduced the biogenesis and functions of ncRNAs, and subsequently summarized the roles and relevant molecular mechanisms of ncRNAs regulating autophagy in myocardial I/R injury. We hope that this review in addition to develop a better understanding of the physiological and pathological roles of ncRNAs, can also lay a foundation for the therapies of myocardial I/R injury, and even for other related cardiovascular diseases.

scholarly journals Circular RNA TTC3 regulates cerebral ischemia-reperfusion injury and neural stem cells by miR-372-3p/TLR4 axis in cerebral infarction

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Bo Yang ◽  
Li’e Zang ◽  
Jingwen Cui ◽  
Linlin Wei
Keyword(s):  
Stem Cells ◽  
Cerebral Ischemia ◽  
Cerebral Infarction ◽  
Neural Stem Cells ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Cerebral Ischemia Reperfusion ◽  
The Impact

Abstract Background Stroke serves as a prevalent cerebrovascular disorder with severe cerebral ischemia/reperfusion (CIR) injury, in which neural stem cells (NSCs) play critical roles in the recovery of cerebral function. Circular RNAs (circRNAs) have been widely found to participate in stroke and NSC modulation. However, the role of circRNA TTC3 (circTTC3) in the regulation of CIR injury and NSCs remains elusive. Here, we aimed to explore the impact of circTTC3 on CIR injury and NSCs. Methods The middle cerebral artery occlusion/repression (MCAO/R) model was established in C57BL/6J mice. The primary astrocytes were isolated from the cerebellum from C57BL/6J mice. The primary NSCs were obtained from rat embryos. The effect of circTTC3 on CIR injury and NSCs was analyzed by TTC staining, qPCR, Western blot, LDH colorimetric kits, MTT assays, Annexin V-FITC Apoptosis Detection Kit, luciferase reporter gene assays, and others in the system. Results Significantly, the expression of circTTC3 was elevated in the MCAO/R mice and oxygen and glucose deprivation (OGD)-treated astrocytes. The depletion of circTTC3 attenuated cerebral infarction, neurological score, and brain water content. The OGD treatment induced apoptosis and the levels of lactate dehydrogenase (LDH) in the astrocytes, in which circTTC3 depletion reduced this phenotype in the system. Moreover, the depletion of circTTC3 promoted the proliferation and upregulated the nestin and β-tubulin III expression in NSCs. Mechanically, circTTC3 was able to sponge miR-372-3p, and miR-372-3p can target Toll-like receptor 4 (TLR4) in NSCs. The miR-372-3p inhibitor or TLR4 overexpression could reverse circTTC3 depletion-mediated astrocyte OGD injury and NSC regulation. Conclusion Thus, we conclude that circTTC3 regulates CIR injury and NSCs by the miR-372-3p/TLR4 axis in cerebral infarction. Our finding presents new insight into the mechanism by which circTTC3 modulates CIR injury and NSC dysfunction. CircTTC3, miR-372-3p, and TLR4 may serve as potential targets for the treatment of CIR injury during stroke.

Circular RNAs are differentially expressed in liver ischemia/reperfusion injury model

2018 ◽  
Vol 119 (9) ◽  
pp. 7397-7405 ◽  
Author(s):  
Zhiqiang Ye ◽  
Qinglei Kong ◽  
Jianhua Han ◽  
Jingyi Deng ◽  
Miaolue Wu ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Differentially Expressed ◽  
Circular Rnas ◽  
Liver Ischemia ◽  
Injury Model

scholarly journals The TWIST1-centered competing endogenous RNA network promotes proliferation, invasion, and migration of lung adenocarcinoma

Oncogenesis ◽  
2019 ◽  
Vol 8 (11) ◽  
Author(s):  
Wenjie Xia ◽  
Qixing Mao ◽  
Bing Chen ◽  
Lin Wang ◽  
Weidong Ma ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Migration And Invasion ◽  
Circular Rnas ◽  
Messenger Rnas ◽  
Competing Endogenous Rna ◽  
Invasion And Migration ◽  
Non Coding Rnas ◽  
And Migration

Abstract The proposed competing endogenous RNA (ceRNA) mechanism suggested that diverse RNA species, including protein-coding messenger RNAs and non-coding RNAs such as long non-coding RNAs, pseudogenes and circular RNAs could communicate with each other by competing for binding to shared microRNAs. The ceRNA network (ceRNET) is involved in tumor progression and has become a hot research topic in recent years. To date, more attention has been paid to the role of non-coding RNAs in ceRNA crosstalk. However, coding transcripts are more abundant and powerful than non-coding RNAs and make up the majority of miRNA targets. In this study, we constructed a mRNA-mRNA related ceRNET of lung adenocarcinoma (LUAD) and identified the highlighted TWIST1-centered ceRNET, which recruits SLC12A5 and ZFHX4 as its ceRNAs. We found that TWIST1/SLC12A5/ZFHX4 are all upregulated in LUAD and are associated with poorer prognosis. SLC12A5 and ZFHX4 facilitated proliferation, migration, and invasion in vivo and in vitro, and their effects were reversed by miR-194–3p and miR-514a-3p, respectively. We further verified that SLC12A5 and ZFHX4 affected the function of TWIST1 by acting as ceRNAs. In summary, we constructed a mRNA-mRNA related ceRNET for LUAD and highlighted the well-known oncogene TWIST1. Then we verified that SLC12A5 and ZFHX4 exert their oncogenic function by regulating TWIST1 expression through a ceRNA mechanism.

scholarly journals Identification of Non-coding RNA Biomarkers in Stress-induced Depression via Comprehensive Analysis of Competing Endogenous RNA Network

2020 ◽  
Author(s):  
xuanjun liu ◽  
Lan Yan ◽  
Chun Lin ◽  
Yiliang Zhang ◽  
Haofei Miao ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Comprehensive Analysis ◽  
Differentially Expressed ◽  
Psychiatric Disease ◽  
Circular Rnas ◽  
Messenger Rnas ◽  
Competing Endogenous Rna ◽  
Non Coding Rna ◽  
Non Coding Rnas ◽  
Promising Perspective

Abstract BackgroundDepression is one of the most common psychiatric disease worldwide. Although the research about the pathogenesis of depression have achieved progress, the detailed effect of non-coding RNAs (ncRNAs) in depression are still not clearly elucidated. This study was aimed to identify non-coding RNA biomarkers in stress-induced depression via comprehensive analysis of competing endogenous RNA networkMethodsIn this present study, we acquired RNA expression from RNA seq expression profile in three mice with depressive-like behaviors using chronic restraint stress paradigm and three C57BL/6J wild-type mice as control mice. ResultsA total of 41 differentially expressed circular RNAs (circRNAs) and 181 differentially expressed messenger RNAs (mRNAs) were up-regulated, and 65 differentially expressed circRNAs and 289 differentially expressed mRNAs were down-regulated, which were selected by a threshold of fold change ≥2 and a p-value < 0.05. Gene Ontology was performed to analyze the biological functions, and we predicted potential signaling pathways based on Kyoto Encyclopedia of Genes and Genomes pathway database. In addition, we constructed a circRNA-microRNA (miRNA)-mRNA regulatory network to further identify non-coding RNAs biomarkers. ConclusionsOur findings provide a promising perspective for further research into molecular mechanisms of depression, and targeting circRNA -mediated competing endogenous RNA (ceRNA) network is a useful strategy to early recognize the depression.

scholarly journals Poly(I:C)-Induced Mesenchymal Stem Cells Protect the Kidney Against Ischemia/Reperfusion Injury via the TLR3/PI3K Pathway

2021 ◽  
Vol 8 ◽  
Author(s):  
Tian Chen ◽  
Yamei Jiang ◽  
Shihao Xu ◽  
Yin Celeste Cheuk ◽  
Jiyan Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Renal Function ◽  
Inflammatory Cytokines ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Pi3k Pathway ◽  
Poly I:C ◽  
Inflammatory Phenotype ◽  
Anti Inflammatory

Objective: To investigate the effect and protective mechanism of mesenchymal stem cell subpopulations on acute kidney injury by establishing a mouse model of renal ischemia-reperfusion injury.Methods: Male C57BL/6 mice were randomly divided into five groups, namely, sham-operation group and those treated with normal saline, untreated mesenchymal stem cells, mesenchymal stem cells treated with lipopolysaccharide (LPS, pro-inflammatory phenotype) and mesenchymal stem cells treated with polyinosinic-polycytidylic acid (poly[I:C], anti-inflammatory phenotype) respectively. The renal function, histopathological damage, circulating inflammation levels and antioxidant capacity of mice were evaluated. The PI3 kinase p85 (PI3K) inhibitor was added into the conventional mesenchymal stem cell cultures in vitro to observe its effects on the secretion of anti-inflammatory cytokines.Results: Mesenchymal stem cells treated with poly(I:C) (anti-inflammatory phenotype) could effectively reduce serum creatinine and blood urea nitrogen, attenuate histopathological damage and apoptosis level, decrease the level of circulating pro-inflammatory cytokines and increase the level of circulating anti-inflammatory cytokines, enhance peroxidase activity and reduce malondialdehyde content at each time point. After the addition of the PI3K inhibitor, the mRNA expression and protein secretion of indoleamine 2,3-dioxygenase 1 and heme oxygenase 1 of various mesenchymal stem cells were significantly reduced, and that of mesenchymal stem cells treated with poly(I:C) (anti-inflammatory phenotype) was more obvious.Conclusions: Polyriboinosinic-polyribocytidylic acid (poly[I:C]), a synthetic double-stranded RNA, whose pretreatment induces mesenchymal stem cells to differentiate into the anti-inflammatory phenotype. Anti-inflammatory mesenchymal stem cells induced by poly(I:C) can better protect renal function, alleviate tissue damage, reduce circulating inflammation levels and enhance antioxidant capacity, and achieve stronger anti-inflammatory effects through the TLR3/PI3K pathway.

The selective poly(ADP)ribose-polymerase 1 inhibitor INO1001 reduces spinal cord injury during porcine aortic cross-clamping-induced ischemia/reperfusion injury

2007 ◽  
Vol 33 (5) ◽  
pp. 845-850 ◽  
Author(s):  
Christian Maier ◽  
Angelika Scheuerle ◽  
Balázs Hauser ◽  
Hubert Schelzig ◽  
Csaba Szabó ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Cord Injury

scholarly journals Protein kinase CK2: a potential therapeutic target for diverse human diseases

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Christian Borgo ◽  
Claudio D’Amore ◽  
Stefania Sarno ◽  
Mauro Salvi ◽  
Maria Ruzzene
Keyword(s):  
Protein Kinase ◽  
Ischemia Reperfusion Injury ◽  
Neurological Diseases ◽  
Ischemia Reperfusion ◽  
Human Diseases ◽  
Host Proteins ◽  
Potential Therapeutic Target ◽  
Human Infections ◽  
Kinase Ck2 ◽  
Diabetes And Obesity

AbstractCK2 is a constitutively active Ser/Thr protein kinase, which phosphorylates hundreds of substrates, controls several signaling pathways, and is implicated in a plethora of human diseases. Its best documented role is in cancer, where it regulates practically all malignant hallmarks. Other well-known functions of CK2 are in human infections; in particular, several viruses exploit host cell CK2 for their life cycle. Very recently, also SARS-CoV-2, the virus responsible for the COVID-19 pandemic, has been found to enhance CK2 activity and to induce the phosphorylation of several CK2 substrates (either viral and host proteins). CK2 is also considered an emerging target for neurological diseases, inflammation and autoimmune disorders, diverse ophthalmic pathologies, diabetes, and obesity. In addition, CK2 activity has been associated with cardiovascular diseases, as cardiac ischemia–reperfusion injury, atherosclerosis, and cardiac hypertrophy. The hypothesis of considering CK2 inhibition for cystic fibrosis therapies has been also entertained for many years. Moreover, psychiatric disorders and syndromes due to CK2 mutations have been recently identified. On these bases, CK2 is emerging as an increasingly attractive target in various fields of human medicine, with the advantage that several very specific and effective inhibitors are already available. Here, we review the literature on CK2 implication in different human pathologies and evaluate its potential as a pharmacological target in the light of the most recent findings.

scholarly journals Protective role of ABCA1 in ischemic preconditioning is mediated by downregulation of miR-33-5p and miR-135-5p

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hye Youn Sung ◽  
Eun Nam Choi ◽  
Jihye Han ◽  
Yun Ju Chae ◽  
Sun-Wha Im ◽  
...  
Keyword(s):  
Ischemic Preconditioning ◽  
Mirna Expression ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Artery Occlusion ◽  
Messenger Rnas ◽  
Apoptosis Pathway ◽  
Mrna Ratio ◽  
Abca1 Expression

AbstractIschemic preconditioning (IPC) significantly reduces ischemia–reperfusion injury in the brain by inducing ischemic tolerance. Although emerging evidence suggests that microRNAs (miRNAs) contribute to the pathogenesis of brain ischemia and IPC-induced neuroprotection, the role of miRNAs and their underlying mechanisms are still unclear. IPC was induced in male C57BL/6 mice by brief bilateral common carotid artery occlusion. After 24 h, mice underwent transient middle cerebral artery occlusion followed by 3 h of reperfusion. Expression levels of messenger RNAs (mRNAs) and proteins were examined in the ipsilateral cortex, and mimics and inhibitors of selective miRNAs were transfected into Neuro-2a cells before oxygen–glucose deprivation (OGD). Post-IPC miRNA expression profiling identified neuroprotection-associated changes in miRNA expression in the ipsilateral cortex after ischemic stroke. Among them, miR-33-5p and miR-135b-5p were significantly downregulated by IPC. Inhibition of miR-33-5p and miR-135b-5p expression protected Neuro-2a cells from OGD-induced apoptosis. Inhibition of these two miRNAs significantly increased mRNA and protein levels of ATP-binding cassette subfamily A member 1 (ABCA1), and a binding assay showed that these two miRNAs showed specificity for Abca1 mRNA. Overexpression of ABCA1 decreased the Bax/Bcl2 mRNA ratio and activation of caspase-9 and caspase-3, whereas knockdown of ABCA1 expression increased the Bax/Bcl2 mRNA ratio and the percentage of Neuro-2a cells with a loss of mitochondrial membrane potential after OGD-treatment. In conclusion, ABCA1 expression is regulated by miR-33-5p and miR-135b-5p. Increased ABCA1 expression following IPC exerts a protective influence against cerebral ischemia via suppression of a mitochondria-dependent apoptosis pathway.

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