Pathophysiology of Long Non-coding RNAs in Ischemic Stroke.
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ABSTRACT:
SUBMITTER: Ren W
PROVIDER: S-EPMC5884949 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Stroke is one of the leading causes of mortality and disability worldwide. Uncovering the cellular and molecular pathophysiological processes in stroke have been a top priority. Long non-coding (lnc) RNAs play critical roles in different kinds of diseases. In recent years, a bulk of aberrantly expressed lncRNAs have been screened out in ischemic stroke patients or ischemia insulted animals using new technologies such as RNA-seq, deep sequencing, and microarrays. Nine specific lncRNAs, antisense non-coding RNA in the INK4 locus (ANRIL), metastasis-associate lung adenocarcinoma transcript 1 (MALAT1), N1LR, maternally expressed gene 3 (MEG3), H19, CaMK2D-associated transcript 1 (C2dat1), Fos downstream transcript (FosDT), small nucleolar RNA host gene 14 (SNHG14), and taurine-upregulated gene 1 (TUG1), were found increased in cerebral ischemic animals and/or oxygen-glucose deprived (OGD) cells. These lncRNAs were suggested to promote cell apoptosis, angiogenesis, inflammation, and cell death. Our Gene Ontology (GO) enrichment analysis predicted that MEG3, H19, and MALAT1 might also be related to functions such as neurogenesis, angiogenesis, and inflammation through mechanisms of gene regulation (DNA transcription, RNA folding, methylation, and gene imprinting). This knowledge may provide a better understanding of the functions and mechanisms of lncRNAs in ischemic stroke. Further elucidating the functions and mechanisms of these lncRNAs in biological systems under normal and pathological conditions may lead to opportunities for identifying biomarkers and novel therapeutic targets of ischemic stroke.
| S-EPMC5833768 | biostudies-literature
Project description:BackgroundThe problem of ischemic stroke (IS) has become increasingly important in recent years, as it ranks first in the structure of disability and mortality, crowding out other vascular diseases. In this regard, the study of this pathology and the search for new therapeutic and diagnostic tools remains an urgent problem of modern medical science and practice. Long non-coding RNAs (lncRNAs)-based therapeutics and diagnostic tools offer a very attractive area of study. Therefore, this systematic review aims at summarizing current knowledge on promising lncRNAs as biomarkers and therapeutic targets for IS exploring original articles and literature reviews on in vivo, in vitro and ex vivo experiments.MethodsThe current systematic review was performed according to PRISMA guidelines. PubMed, MEDLINE and Google Scholar databases were comprehensively explored to perform the article search.Results34 eligible studies were included and analyzed: 25 focused on lncRNAs-based therapeutics and 9 on lncRNAs-based diagnosis. We found 31 different lncRNAs tested as potential therapeutic and diagnostic molecules in cells and animal model experiments. Among all founded lncRNA-based therapeutics and non-invasive diagnostic tools, nuclear enriched abundant transcript 1 (NEAT1) emerged to be the most investigated and proposed as a potential molecule for IS diagnosis and treatment.ConclusionsOur analysis provides a snapshot of the current scenario regarding the lncRNAs as therapeutic molecules and biomarkers in IS. Different lncRNAs are differently expressed in IS, and some of them can be further evaluated as therapeutic targets and biomarkers for early diagnosis and prognosis or treatment response. However, despite many efforts, none of the selected studies go beyond preclinical studies, and their translation into clinical practice seems to be very premature.
| S-EPMC9508273 | biostudies-literature
Project description:Long non-coding RNAs (lncRNAs) have been evidenced to be associated with the development of multiple diseases. However, the expression pattern and function of lncRNAs in acute ischemic stroke remain unclear. To determine the differential expression of lncRNAs in acute ischemic stroke, we analyzed the expression profile of lncRNAs by high-throughput sequencing analysis. Gene Ontology (GO) and pathway analyses were employed to analyze the gene function and identify enriched pathways of the differentially expressed lncRNAs. We also built an lncRNA-mRNA expression correlation network and verified the interactions of selected lncRNAs in acute ischemic stroke. To further confirm the results of the expression profile, 6 differentially expressed lncRNAs were randomly selected and quantitative RT-PCR (qRT-PCR) performed. We identified 44,578 aberrantly expressed lncRNAs, including 228 upregulated and 16 downregulated lncRNAs. The qRT-PCR results showed that ENSG00000269900, ENSG00000196559, ENSG00000202198, ENSG00000226482, ENSG00000260539 (up), and XLOC_013994_2 (down) were abnormally expressed, which was consistent with the sequencing results. The upregulated expression of lncRNA ENSG00000226482 may activate the adipocytokine signaling pathway, resulting in acute ischemia stroke. In summary, we analyzed the lncRNAs expression profile in acute ischemic stroke patients and identified the functions and enriched metabolic pathways, proposing new insights into the diagnostic and therapeutic biomarkers for this disease.
| S-EPMC7738114 | biostudies-literature
Project description:Objective:Ischemic stroke and myocardial infarction are 2 of the leading causes of mortality. Both conditions are caused by arterial occlusion, resulting in ischemic necrosis of the cells in the cortex and heart. Long non-coding RNAs (lncRNAs) are a group of non-coding RNAs longer than 200 nucleotides without protein-coding potential. Thousands of lncRNAs have been identified but their involvement in ischemic stroke and myocardial infarction has not been studied extensively. Therefore, this study aimed to identify the role of lncRNAs, particularly those that are commonly altered in these two ischemic injuries. Methods:We combined diverse RNA sequencing data obtained from public databases and performed extensive bioinformatics analyses to determine reliable lncRNAs commonly identified from these datasets. Using sequence analysis, we also detected the lncRNAs that may act as microRNA (miRNA) regulators. Results:We found several altered lncRNAs that were common in ischemic stroke and myocardial infarction models. Some of these lncRNAs, including zinc finger NFX1-type containing 1 antisense RNA 1 and small nucleolar RNA host gene 1, were previously reported to be involved in the pathogenesis of each of these models. Interestingly, several lncRNAs had binding sites for miRNAs that were previously reported to be involved in the hypoxic response, suggesting the possible role of these lncRNAs as regulators in ischemic responses. Conclusion:The lncRNAs identified in this study will be useful in determining the regulatory networks in ischemic stroke and myocardial infarction and in identifying potential specific markers for each of these ischemic diseases.
| S-EPMC7521976 | biostudies-literature
Project description:Long non?coding RNAs (lncRNAs) represent potential biomarkers for the diagnosis and treatment of various diseases; however, the role of circulating acute ischemic stroke (AIS)?related lncRNAs remains relatively unknown. The present study aimed to screen crucial lncRNAs for AIS based on the competing endogenous RNA (ceRNA) hypothesis. The expression profile datasets for one mRNA, accession no. GSE16561, and four microRNAs (miRNAs), accession nos. GSE95204, GSE86291, GSE55937 and GSE110993, were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs), lncRNAs (DELs), and miRNAs (DEMs) were identified, and ClusterProfiler was used to interpret the function of the DEGs. Based on the protein?protein interaction (PPI) network and module analyses, hub DEGs were identified. A ceRNA network was established based on miRNA?mRNA or miRNA?lncRNA interaction pairs. In total, 2,041 DEGs and 5 DELs were identified between the AIS and controls samples in GSE16561, and 10 DEMs between at least two of the four miRNA expression profiles. A PPI network was constructed with 1,235 DEGs, among which 20 genes were suggested to be hub genes. The hub genes paxillin (PXN), FYN?proto?oncogene, Src family tyrosine kinase (FYN), ras homolog family member A (RHOA), STAT1, and growth factor receptor?bound protein 2 (GRB2), were amongst the most significantly enriched modules extracted from the PPI network. Functional analysis revealed that these hub genes were associated with inflammation?related signaling pathways. An AIS?related ceRNA network was constructed, in which 4 DELs were predicted to function as ceRNAs for 9 DEMs, to regulate the five identified hub genes; that is, minichromosome maintenance complex component 3 associated protein?antisense RNA 1 (MCM3AP?AS1)/long intergenic non?protein coding RNA 1089 (LINC01089)/hsa?miRNA (miR)?125a/FYN, inositol?tetrakisphosphate 1?kinase?antisense RNA 1 (ITPK1?AS1)/hsa?let?7i/RHOA/GRB2/STAT1, and human leukocyte antigen complex group 27 (HCG27)/hsa?-miR?19a/PXN interaction axes. In conclusion, MCM3AP?AS1, LINC01089, ITPK1?AS1, and HCG27 may represent new biomarkers and underlying targets for the treatment of AIS.
| S-EPMC7453507 | biostudies-literature
Project description:Bone remodeling is uncoupled in the multiple myeloma (MM) bone marrow niche, resulting in enhanced osteoclastogenesis responsible of MM-related bone disease (MMBD). Several studies have disclosed the mechanisms underlying increased osteoclast formation and activity triggered by the various cellular components of the MM bone marrow microenvironment, leading to the identification of novel targets for therapeutic intervention. In this regard, recent attention has been given to non-coding RNA (ncRNA) molecules, that finely tune gene expression programs involved in bone homeostasis both in physiological and pathological settings. In this review, we will analyze major signaling pathways involved in MMBD pathophysiology, and report emerging evidence of their regulation by different classes of ncRNAs.
| S-EPMC7549375 | biostudies-literature
Project description:Large-scale analyses of mammalian transcriptomes have identified a significant number of different RNA molecules that are not translated into protein. In fact, the use of new sequencing technologies has identified that most of the genome is transcribed, producing a heterogeneous population of RNAs which do not encode for proteins (ncRNAs). Emerging data suggest that these transcripts influence the development of cardiovascular disease. The best characterized non-coding RNA family is represented by short highly conserved RNA molecules, termed microRNAs (miRNAs), which mediate a process of mRNA silencing through transcript degradation or translational repression. These microRNAs (miRNAs) are expressed in cardiovascular tissues and play key roles in many cardiovascular pathologies, such as coronary artery disease (CAD) and heart failure (HF). Potential links between other ncRNAs, like long non-coding RNA, and cardiovascular disease are intriguing but the functions of these transcripts are largely unknown. Thus, the functional characterization of ncRNAs is essential to improve the overall understanding of cellular processes involved in cardiovascular diseases in order to define new therapeutic strategies. This review outlines the current knowledge of the different ncRNA classes and summarizes their role in cardiovascular development and disease.
| S-EPMC3821599 | biostudies-literature
Project description:Epilepsy is a common neurologic disorder. The underlying pathological processes include synaptic strength, inflammation, ion channels, and apoptosis. Acting as epigenetic factors, non-coding RNAs (ncRNAs) participate in the regulation of pathophysiologic processes of epilepsy and are dysregulated during epileptogenesis. Aberrant expression of ncRNAs are observed in epilepsy patients and animal models of epilepsy. Furthermore, ncRNAs might also be used as biomarkers for diagnosis and the prognosis of treatment response in epilepsy. In this review, we will summarize the role of ncRNAs in the pathophysiology of epilepsy and the putative utilization of ncRNAs as diagnostic biomarkers and therapeutic targets.
| S-EPMC5554344 | biostudies-literature
Project description:Non-coding RNAs (ncRNAs) have critical role in the pathophysiology as well as recovery after ischemic stroke. ncRNAs, particularly microRNAs, and the long non-coding RNAs (lncRNAs) are critical for angiogenesis and neuroprotection, and they have been suggested to be therapeutic, diagnostic and prognostic tools in cerebrovascular diseases, including stroke. Moreover, exosomes have been considered as nanocarriers capable of transferring various cargos, such as lncRNAs and miRNAs to recipient cells, with prominent inter-cellular roles in the mediation of neuro-restorative events following strokes and neural injuries. In this review, we summarize the pathogenic role of ncRNAs and exosomal ncRNAs in the stroke.
| S-EPMC8222190 | biostudies-literature
Project description:Acute myocardial infarction (AMI) is a life?threatening disease and seriously influences patient quality of life. Long non?coding RNAs (lncRNAs), an emerging class of non?coding genes, have attracted attention in research, however, whether lncRNAs serve a function in acute ischemic hypoxia remains to be elucidated. In the present study, an lncRNA microarray was used to analyze differential lncRNA expression in acute ischemic hypoxia. A total of 323 lncRNAs were identified, 168 of which were upregulated and 155 of which were downregulated. Gene Ontology and Pathway analyses were also used to identify the potential functions of dysregulated lncRNAs; it was predicted that these dysregulated lncRNAs may contribute to the initiation of AMI. It was demonstrated that an lncRNA termed sloyfley may influence acute ischemic hypoxia through its neighboring gene Peg3, which has been linked to brain ischemia hypoxia. In summary, the present study identified numerous lncRNAs, which may provide further opportunities for the development of novel therapeutic strategies.
| S-EPMC6297740 | biostudies-literature