scholarly journals MicroRNAs as Diagnostic and Prognostic Biomarkers in Ischemic Stroke—A Comprehensive Review and Bioinformatic Analysis

Cells ◽  
2018 ◽  
Vol 7 (12) ◽  
pp. 249 ◽  
Author(s):  
Ceren Eyileten ◽  
Zofia Wicik ◽  
Salvatore De Rosa ◽  
Dagmara Mirowska-Guzel ◽  
Aleksandra Soplinska ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Blood Coagulation ◽  
Platelet Activation ◽  
Target Genes ◽  
Neurological Diseases ◽  
Mirna Gene ◽  
Bioinformatic Analysis ◽  
Prognostic Biomarkers ◽  
Detection Methods ◽  
Gene Target

Stroke is the second-most common cause of death worldwide. The pathophysiology of ischemic stroke (IS) is related to inflammation, atherosclerosis, blood coagulation, and platelet activation. MicroRNAs (miRNAs) play important roles in physiological and pathological processes of neurodegenerative diseases and progression of certain neurological diseases, such as IS. Several different miRNAs, and their target genes, are recognized to be involved in the pathophysiology of IS. The capacity of miRNAs to simultaneously regulate several target genes underlies their unique value as diagnostic and prognostic markers in IS. In this review, we focus on the role of miRNAs as diagnostic and prognostic biomarkers in IS. We discuss the most common and reliable detection methods available and promising tests currently under development. We also present original results from bioinformatic analyses of published results, identifying the ten most significant genes (HMGB1, YWHAZ, PIK3R1, STAT3, MAPK1, CBX5, CAPZB, THBS1, TNFRSF10B, RCOR1) associated with inflammation, blood coagulation, and platelet activation and targeted by miRNAs in IS. Additionally, we created miRNA-gene target interaction networks based on Gene Ontology (GO) information derived from publicly available databases. Among our most interesting findings, miR-19a-3p is the most widely modulated miRNA across all selected ontologies and might be proposed as novel biomarker in IS to be tested in future studies.

scholarly journals Identification and Insilico Analysis of Retinoblastoma Serum microRNA Profile and Gene Targets towards Prediction of Novel Serum Biomarkers

2013 ◽  
Vol 7 ◽  
pp. BBI.S10501 ◽  
Author(s):  
Madhu Beta ◽  
Nalini Venkatesan ◽  
Madavan Vasudevan ◽  
Umashankar Vetrivel ◽  
Vikas Khetan ◽  
...  
Keyword(s):  
Regulatory Networks ◽  
Target Genes ◽  
Mirna Gene ◽  
Target Prediction ◽  
Fold Change ◽  
Serum Samples ◽  
Gene Target ◽  
Qrt Pcr ◽  
Serum Microrna ◽  
Oncogenic Mirnas

Retinoblastoma (RB) is a malignant tumor of the retina seen in children, and potential non invasive biomarkers are in need for rapid diagnosis and for prognosticating the therapy. This study was undertaken to identify the differentially expressed miRNAs in the serum of children with RB in comparison with the normal age matched serum, to analyze its concurrence with the existing RB tumor miRNA profile, to identify its novel gene targets specific to RB, and to study the expression of a few of the identified oncogenic miRNAs in the advanced stage primary RB patient's serum sample. MiRNA profiling was performed on 14 pooled serum from children with advanced RB and 14 normal age matched serum samples, wherein 21 miRNAs were found to be upregulated (fold change ≥ +2.0, P ≤ 0.05) and 24 to be downregulated (fold change ≤ –2.0, P ≤ 0.05). Furthermore, intersection of 59 significantly deregulated miRNAs identified from RB tumor profiles with that of miRNAs detected in serum profile revealed that 33 miRNAs had followed a similar deregulation pattern in RB serum. Later we validated a few of the miRNAs (miRNA 17-92) identified by microarray in the RB patient serum samples (n = 20) by using qRT-PCR. Expression of the oncogenic miRNAs, miR-17, miR-18a, and miR-20a by qRT-PCR was significant in the serum samples exploring the potential of serum miRNAs identification as noninvasive diagnosis. Moreover, from miRNA gene target prediction, key regulatory genes of cell proliferation, apoptosis, and positive and negative regulatory networks involved in RB progression were identified in the gene expression profile of RB tumors. Therefore, these identified miRNAs and their corresponding target genes could give insights on potential biomarkers and key events involved in the RB pathway.

Enhanced platelet activation by prolactin in patients with ischemic stroke

2004 ◽  
Vol 112 (S 1) ◽  
Author(s):  
H Wallaschofski ◽  
M Eigenthaler ◽  
E Hild ◽  
A Kobsar ◽  
A Siegemund ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Platelet Activation

scholarly journals ATRT-03. IDENTIFICATION OF microRNA-BASED PROGNOSTIC BIOMARKERS AND CANDIDATE THERAPEUTIC AGENTS FOR ATYPICAL TERATOID/RHABDOID TUMOR

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii275-iii276
Author(s):  
Yang Zhang ◽  
Jianguo Xu
Keyword(s):  
Target Genes ◽  
Kinase Inhibitor ◽  
Therapeutic Agents ◽  
Rhabdoid Tumor ◽  
Janus Kinase ◽  
Prognostic Biomarkers ◽  
Atypical Teratoid Rhabdoid Tumor ◽  
Overlapping Genes ◽  
Hub Genes ◽  
Atypical Teratoid

Abstract BACKGROUND MicroRNA (miRNA) has been found to be involved in development of many malignant pediatric brain tumors, including atypical teratoid/rhabdoid tumor (AT/RT) that is highly aggressive and carries a dismal prognosis. The current study investigated the potential value of miRNAs and pivotal genes associated with AT/RT using bioinformatics analysis, aiming to identify new prognostic biomarkers and candidate drugs for AT/RT patients. METHODS Differentially expressed miRNAs (DEMs) and genes (DEGs) between AT/RT and normal control samples were obtained from GEO database. The target genes of DEMs were predicted via TargetScanHuman7.2 and miRDB, and then intersected with DEGs. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses of overlapping genes were conducted, followed by construction of protein-protein interaction network. Hub genes were determined by Cytoscape software, and their prognostic values were evaluated using Kaplan-Meier analysis. Connectivity Map database was used to identify latent therapeutic agents. RESULTS A total of 11 DEMs (hsa-miR-1224-5p, hsa-miR-128-3p, hsa-miR-17-5p, hsa-miR-18b-5p, hsa-miR-29c-5p, hsa-miR-329-3p, hsa-miR-379-5p, hsa-miR-433-3p, hsa-miR-488-5p, hsa-miR-656-3p and hsa-miR-885-5p) were screened. By intersecting 3275 predicted target genes and 925 DEGs, we finally identified 226 overlapping genes that were enriched in pathways in cancer and MAPK signaling pathway. Four hub genes (GRIA2, NRXN1, SLC6A1 and SYT1) were significantly associated with the overall survival of AT/RT patients. Candidate drugs included histone deacetylase inhibitor (givinostat), DNA synthesis inhibitor (floxuridine), cyclin-dependent kinase inhibitor (purvalanol) and janus kinase inhibitor (lestaurtinib). CONCLUSION In summary, this study systematically analyzed AT/RT-related miRNAs and pivotal genes to provide novel prognostic biomarkers and potential therapeutic agents.

scholarly journals Sex-Biased lncRNA Signature in Fetal Growth Restriction (FGR)

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 921
Author(s):  
Aleksandra Lipka ◽  
Jan Pawel Jastrzebski ◽  
Lukasz Paukszto ◽  
Karol Gustaw Makowczenko ◽  
Elzbieta Lopienska-Biernat ◽  
...  
Keyword(s):  
Fetal Growth ◽  
Fetal Growth Restriction ◽  
Target Genes ◽  
Active Regions ◽  
Bioinformatic Analysis ◽  
Growth Restriction ◽  
Differentially Expressed ◽  
Circular Rnas ◽  
Differential Analysis ◽  
Protein Coding

Impaired fetal growth is one of the most important causes of prematurity, stillbirth and infant mortality. The pathogenesis of idiopathic fetal growth restriction (FGR) is poorly understood but is thought to be multifactorial and comprise a range of genetic causes. This research aimed to investigate non-coding RNAs (lncRNAs) in the placentas of male and female fetuses affected by FGR. RNA-Seq data were analyzed to detect lncRNAs, their potential target genes and circular RNAs (circRNAs); a differential analysis was also performed. The multilevel bioinformatic analysis enabled the detection of 23,137 placental lncRNAs and 4263 of them were classified as novel. In FGR-affected female fetuses’ placentas (ff-FGR), among 19 transcriptionally active regions (TARs), five differentially expressed lncRNAs (DELs) and 12 differentially expressed protein-coding genes (DEGs) were identified. Within 232 differentially expressed TARs identified in male fetuses (mf-FGR), 33 encompassed novel and 176 known lncRNAs, and 52 DEGs were upregulated, while 180 revealed decreased expression. In ff-FGR ACTA2-AS1, lncRNA expression was significantly correlated with five DEGs, and in mf-FGR, 25 TARs were associated with DELs correlated with 157 unique DEGs. Backsplicing circRNA processes were detected in the range of H19 lncRNA, in both ff- and mf-FGR placentas. The performed global lncRNAs characteristics in terms of fetal sex showed dysregulation of DELs, DEGs and circRNAs that may affect fetus growth and pregnancy outcomes. In female placentas, DELs and DEGs were associated mainly with the vasculature, while in male placentas, disturbed expression predominantly affected immune processes.

scholarly journals The acute transcriptional responses to dietary methionine restriction are triggered by inhibition of ternary complex formation and linked to Erk1/2, mTOR, and ATF4

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kirsten P. Stone ◽  
Sujoy Ghosh ◽  
Jean Paul Kovalik ◽  
Manda Orgeron ◽  
Desiree Wanders ◽  
...  
Keyword(s):  
Stress Response ◽  
Complex Formation ◽  
Ternary Complex ◽  
Target Genes ◽  
Bioinformatic Analysis ◽  
Transcriptional Responses ◽  
Metabolomics Data ◽  
Ternary Complex Formation ◽  
Methionine Restriction

AbstractThe initial sensing of dietary methionine restriction (MR) occurs in the liver where it activates an integrated stress response (ISR) that quickly reduces methionine utilization. The ISR program is regulated in part by ATF4, but ATF4’s prototypical upstream regulator, eIF2α, is not acutely activated by MR. Bioinformatic analysis of RNAseq and metabolomics data from liver samples harvested 3 h and 6 h after initiating MR shows that general translation is inhibited at the level of ternary complex formation by an acute 50% reduction of hepatic methionine that limits formation of initiator methionine tRNA. The resulting ISR is induced by selective expression of ATF4 target genes that mediate adaptation to reduced methionine intake and return hepatic methionine to control levels within 4 days of starting the diet. Complementary in vitro experiments in HepG2 cells after knockdown of ATF4, or inhibition of mTOR or Erk1/2 support the conclusion that the early induction of genes by MR is partially dependent on ATF4 and regulated by both mTOR and Erk1/2. Taken together, these data show that initiation of dietary MR induces an mTOR- and Erk1/2-dependent stress response that is linked to ATF4 by the sharp, initial drop in hepatic methionine and resulting repression of translation pre-initiation.

scholarly journals Effects of Clopidogrel and Aspirin in Combination Versus Aspirin Alone on Platelet Activation and Major Receptor Expression in Patients After Recent Ischemic Stroke

Stroke ◽  
2005 ◽  
Vol 36 (10) ◽  
pp. 2289-2292 ◽  
Author(s):  
Victor L. Serebruany ◽  
Alex I. Malinin ◽  
Wendy Ziai ◽  
Alex N. Pokov ◽  
Deepak L. Bhatt ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Platelet Activation ◽  
Receptor Expression

Abstract WMP30: Circulating MicroRNAs as Potential Novel Diagnostic Biomarkers for Ruptured Intracranial Aneurysm

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Zhang Xin ◽  
Liu L Ping
Keyword(s):  
Intracranial Aneurysm ◽  
Target Genes ◽  
Bioinformatic Analysis ◽  
Aneurysm Rupture ◽  
Pathological Process ◽  
Differentially Expressed ◽  
Diagnostic Biomarkers ◽  
Ruptured Intracranial Aneurysm ◽  
Novel Biomarkers ◽  
Aneurysm Development

Background and Objective: MicroRNAs have been shown to regulate in several pathological process of intracranial aneurysms. The study aimed to estimate whether miRNAs have the potential to become novel biomarkers for intracranial aneurysm rupture. Materials and methods Forty-five ruptured intracranial aneurysm patients were enrolled according to the inclusion criteria, meanwhile thirty-five healthy individuals were recruited in this study. Differentially expressed plasma miRNA profiles were screened in five pairs of patients and controls in microarray study. Then validation was performed in the rest of the objects using quantitative real-time PCR assays. Results: Fourteen significantly changed miRNAs were screened out from patients with aneurysms compared with healthy controls. More than three thousand target genes related to these disregulated miRNAs were found and bioinformatic analysis revealed that these miRNA were involved in intracranial aneurysm development and rupture. Ultimately four miRNAs from screening profile and one supplementary miRNA were demonstrated to be significantly altered. Conclusion: We demonstrated that several miRNAs were differentially expressed among ruptured aneurysm patients and healthy participants, and plasma miRNAs may be novel diagnostic biomarkers in intracranial aneurysm rupture.

Elevation of MicroRNA-126 Levels in Intracranial Aneurysm and Bioinformatic Analysis of Potential Molecular Mechanisms

2021 ◽  
Vol 11 (4) ◽  
pp. 573-579
Author(s):  
Pan Huang ◽  
Min Xu ◽  
Xiao-Ying He
Keyword(s):  
Intracranial Aneurysm ◽  
Peripheral Blood ◽  
Target Gene ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Kegg Pathway ◽  
Bioinformatic Analysis ◽  
Control Group ◽  
Potential Target ◽  
Fas Signaling

The study is to investigation of microRNA-126 levels in patients with intracranial aneurysm and bioinformatic analysis of the molecular mechanisms involved. A total of 166 patients with ICA who were hospitalized or examined in our hospital from September 2015 to December 2017 were used as the experimental group (ICA group). This group included 120 patients with unruptured intracranial aneurysm (UICA; UICA group) and 46 patients with ruptured intracranial aneurysm (RICA); RICA group). The UICA group was further subdivided into 42 surgical groups (S group) and 78 nonsurgical groups (NS group). Sixty-three normal people without intracranial aneurysms were selected as the control group. RT-PCR was used to quantitatively detect the relative expression of microRNA- 126 in peripheral blood mononuclear cells at the time of admission and immediately after surgery. The UCSC database was used to analyze the gene locus and homology of microRNA-126. The TargetScan database and CoMeTa database were used to predict the potential target genes of microRNA-126. The DAVID database was used to enrich the function of potential target genes of microRNA-126 (GO enrichment) and KEGG pathway enrichment for analysis. The expression level of microRNA-126 in peripheral blood was significantly higher in the ICA group than in the control group (P <0.01), significantly higher in the RICA group than in the UICA group (P <0.05). Expression was also higher in the NS group than in the S group but the difference was nonsignificant (P >0.05). A total of 15 potential target genes including ITGA6, CRK, PCDH7, and ADAM9 were identified through the target gene prediction software and GO analysis and KEGG pathway analysis showed that the function of the microRNA-126 target gene was mainly focused on protein binding and the FAS signaling pathway. In Conclusion the microRNA-126 is up-regulated in ICA patients and affects ICA by regulating multiple target genes in the FAS signaling pathway.

MSC 2021 Virtual E-Abstract

2021 ◽  
Vol 3 (3) ◽  
pp. 36
Author(s):  
Malaysian Stroke Conference
Keyword(s):  
Ischemic Stroke ◽  
Target Genes

1. Key Mirnas And Target Genes For Ischemic Stroke.

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