The Role of Micrornas in Regulating Redox Modulation in Bipolar Disorder

2017 ◽  
Vol 41 (S1) ◽  
pp. S119-S119
Author(s):  
H. Kim ◽  
K. Tyryshkin ◽  
N. Elmi ◽  
V. Oliviera ◽  
A. Andreazza ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Transcription Factors ◽  
In Silico ◽  
Target Genes ◽  
In Silico Analysis ◽  
Machine Learning Algorithms ◽  
Validation Dataset ◽  
Control Group ◽  
Redox Modulation ◽  
Validation Experiment

IntroductionAlterations in redox modulation are consistently reported in bipolar disorder (BD). MicroRNAs are targeted regulators of gene expression.Objectives and aimsWe aimed to examine if microRNAs that target redox modulators can discriminate between BD and healthy controls.MethodsData from brains of individuals with and without BD were obtained from Array Collection datasets. MicroRNAs targeting redox modulators were assessed for their ability to discriminate BD from the control group using machine-learning algorithms. Methylation of microRNAs, expression of their transcription factors and redox targets were assessed with ANCOVA with FDR correction. For validation, we acquired plasma samples belonging to 2 families of individuals with and without BD (n = 9). Plasma microRNAs were sequenced using the Ion Total RNA Sequencing Kit (Thermo Fisher Scientific), and microRNAs identified from the in silico analysis were examined in the validation dataset.ResultsWe identified 5 miRNAs (hsa-miR-299, hsa-miR-125a, hsa-miR-145, hsa-miR-30b, hsa-miR424) that were common in two of the four in silico datasets. Target genes glutathione peroxidase 4, ATP5A1, ATP5G1, NDUFS1, NDUFC2, and catalase were expressed at different levels between BD and the control group. Furthermore, our results showed that transcription factors CTCF and USF1 might control the expression of hsa-miR-145, while methylation differences were not found. Finally, hsa-miR-30b was significantly increased in the plasma of patients with BD compared to controls in the validation experiment.ConclusionsOur study demonstrates that microRNAs may have an important role in the initiation of redox changes in BD.Disclosure of interestThe authors have not supplied their declaration of competing interest.

In silico analysis and prediction of transcription factors of the proteins interacting with astrocyte elevated gene-1

2021 ◽  
Vol 92 ◽  
pp. 107478
Author(s):  
Sushmitha Sriramulu ◽  
Suman K. Nandy ◽  
Harsha Ganesan ◽  
Antara Banerjee ◽  
Surajit Pathak
Keyword(s):  
Transcription Factors ◽  
In Silico ◽  
In Silico Analysis ◽  
Silico Analysis

scholarly journals Characterization and risk association of polymorphisms in Aurora kinases A, B and C with genetic susceptibility to gastric cancer development

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Aner Mesic ◽  
Marija Rogar ◽  
Petra Hudler ◽  
Nurija Bilalovic ◽  
Izet Eminovic ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Transcription Factors ◽  
In Silico ◽  
In Silico Analysis ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Mitotic Kinases ◽  
Genes Encoding ◽  
Silico Analysis ◽  
Control Study

Abstract Background Single nucleotide polymorphisms (SNPs) in genes encoding mitotic kinases could influence development and progression of gastric cancer (GC). Methods Case-control study of nine SNPs in mitotic genes was conducted using qPCR. The study included 116 GC patients and 203 controls. In silico analysis was performed to evaluate the effects of polymorphisms on transcription factors binding sites. Results The AURKA rs1047972 genotypes (CT vs. CC: OR, 1.96; 95% CI, 1.05–3.65; p = 0.033; CC + TT vs. CT: OR, 1.94; 95% CI, 1.04–3.60; p = 0.036) and rs911160 (CC vs. GG: OR, 5.56; 95% CI, 1.24–24.81; p = 0.025; GG + CG vs. CC: OR, 5.26; 95% CI, 1.19–23.22; p = 0.028), were associated with increased GC risk, whereas certain rs8173 genotypes (CG vs. CC: OR, 0.60; 95% CI, 0.36–0.99; p = 0.049; GG vs. CC: OR, 0.38; 95% CI, 0.18–0.79; p = 0.010; CC + CG vs. GG: OR, 0.49; 95% CI, 0.25–0.98; p = 0.043) were protective. Association with increased GC risk was demonstrated for AURKB rs2241909 (GG + AG vs. AA: OR, 1.61; 95% CI, 1.01–2.56; p = 0.041) and rs2289590 (AC vs. AA: OR, 2.41; 95% CI, 1.47–3.98; p = 0.001; CC vs. AA: OR, 6.77; 95% CI, 2.24–20.47; p = 0.001; AA+AC vs. CC: OR, 4.23; 95% CI, 1.44–12.40; p = 0.009). Furthermore, AURKC rs11084490 (GG + CG vs. CC: OR, 1.71; 95% CI, 1.04–2.81; p = 0.033) was associated with increased GC risk. A combined analysis of five SNPs, associated with an increased GC risk, detected polymorphism profiles where all the combinations contribute to the higher GC risk, with an OR increased 1.51-fold for the rs1047972(CT)/rs11084490(CG + GG) to 2.29-fold for the rs1047972(CT)/rs911160(CC) combinations. In silico analysis for rs911160 and rs2289590 demonstrated that different transcription factors preferentially bind to polymorphic sites, indicating that AURKA and AURKB could be regulated differently depending on the presence of particular allele. Conclusions Our results revealed that AURKA (rs1047972 and rs911160), AURKB (rs2241909 and rs2289590) and AURKC (rs11084490) are associated with a higher risk of GC susceptibility. Our findings also showed that the combined effect of these SNPs may influence GC risk, thus indicating the significance of assessing multiple polymorphisms, jointly. The study was conducted on a less numerous but ethnically homogeneous Bosnian population, therefore further investigations in larger and multiethnic groups and the assessment of functional impact of the results are needed to strengthen the findings.

scholarly journals MicroRNA-based regulation of genomics and transcriptomics of inflammatory cytokines in COVID-19

2021 ◽  
Author(s):  
Manoj Khokhar ◽  
Sojit Tomo ◽  
Purvi Purohit
Keyword(s):  
Transcription Factors ◽  
Inflammatory Response ◽  
In Silico ◽  
Wide Spectrum ◽  
Interaction Network ◽  
In Silico Analysis ◽  
Enrichment Analysis ◽  
Microarray Dataset ◽  
Therapeutic Strategies ◽  
Protein Protein Interaction

Background: Coronavirus disease 2019 is characterized by the elevation of a wide spectrum of inflammatory mediators which are associated with poor disease outcomes. We aimed at an in-silico analysis of regulatory microRNA and their transcription factors (TF) for these inflammatory genes that may help to devise potential therapeutic strategies in the future. Methods: The cytokine regulating immune-expressed genes (CRIEG) were sorted from literature and GEO microarray dataset and their co-differentially expressed miRNA and transcription factors were predicted from publicly available databases. Enrichment analysis was done through mienturnet, MiEAA, and Gene Ontology, and pathways predicted by KEGG and Reactome pathways. The functional and regulatory features were analyzed and visualized through Cytoscape. Results: Sixteen CRIEG were observed to have a significant protein-protein interaction network. The ontological analysis revealed significantly enriched pathways for biological processes, molecular functions, and cellular components. The search performed in the miRNA database yielded 10 miRNAs that are significantly involved in the regulation of these genes and their transcription factors. Conclusion: An In-Silico representation of a network involving miRNAs, CRIEGs, and TF which take part in the inflammatory response in COVID-19 has been elucidated. These regulatory factors may have potentially critical roles in the inflammatory response in COVID-19 and may be explored further for the development of targeted therapeutic strategies and mechanistic validation.

scholarly journals FRUITFULL Is a Repressor of Apical Hook Opening in Arabidopsis thaliana

2020 ◽  
Vol 21 (17) ◽  
pp. 6438
Author(s):  
Miriam Führer ◽  
Angelika Gaidora ◽  
Peter Venhuizen ◽  
Jedrzej Dobrogojski ◽  
Chloé Béziat ◽  
...  
Keyword(s):  
Arabidopsis Thaliana ◽  
In Silico ◽  
Target Genes ◽  
Growth Promotion ◽  
In Silico Analysis ◽  
Regulatory Elements ◽  
Suitable Model ◽  
Differential Growth ◽  
Apical Hook ◽  
Growth Transitions

Plants adjust their architecture to a constantly changing environment, requiring adaptation of differential growth. Despite their importance, molecular switches, which define growth transitions, are largely unknown. Apical hook development in dark grown Arabidopsis thaliana (A. thaliana) seedlings serves as a suitable model for differential growth transition in plants. Here, we show that the phytohormone auxin counteracts the light-induced growth transition during apical hook opening. We, subsequently, identified genes which are inversely regulated by light and auxin. We used in silico analysis of the regulatory elements in this set of genes and subsequently used natural variation in gene expression to uncover correlations between underlying transcription factors and the in silico predicted target genes. This approach uncovered that MADS box transcription factor AGAMOUS-LIKE 8 (AGL8)/FRUITFULL (FUL) modulates apical hook opening. Our data shows that transient FUL expression represses the expression of growth stimulating genes during early phases of apical hook development and therewith guards the transition to growth promotion for apical hook opening. Here, we propose a role for FUL in setting tissue identity, thereby regulating differential growth during apical hook development.

scholarly journals Chondroitin sulfate degradation and eicosanoid metabolism pathways are impaired in focal segmental glomerulosclerosis: Experimental confirmation of an in silico prediction

Bioimpacts ◽  
2019 ◽  
Vol 9 (2) ◽  
pp. 89-95
Author(s):  
Shiva Kalantari ◽  
Mohammad Naji ◽  
Mohsen Nafar ◽  
Hootan Yazdani-Kachooei ◽  
Nasrin Borumandnia ◽  
...  
Keyword(s):  
Chondroitin Sulfate ◽  
Focal Segmental Glomerulosclerosis ◽  
In Silico ◽  
Target Genes ◽  
In Silico Analysis ◽  
Non Invasive ◽  
Segmental Glomerulosclerosis ◽  
Eicosanoid Metabolism ◽  
Cox 2 ◽  
Primary Glomerular Disease

Introduction: Focal segmental glomerulosclerosis (FSGS), the most common primary glomerular disease, is a diverse clinical entity that occurs after podocyte injury. Although numerous studies have suggested molecular pathways responsible for the development of FSGS, many still remain unknown about its pathogenic mechanisms. Two important pathways were predicted as candidates for the pathogenesis of FSGS in our previous in silico analysis, whom we aim to confirm experimentally in the present study. Methods: The expression levels of 4 enzyme genes that are representative of "chondroitin sulfate degradation" and "eicosanoid metabolism" pathways were investigated in the urinary sediments of biopsy-proven FSGS patients and healthy subjects using real-time polymerase chain reaction (RT-PCR). These target genes were arylsulfatase, hexosaminidase, cyclooxygenase-2 (COX-2), and prostaglandin I2 synthase. The patients were sub-divided into 2 groups based on the range of proteinuria and glomerular filtration rate and were compared for variation in the expression of target genes. Correlation of target genes with clinical and pathological characteristics of the disease was calculated and receiver operating characteristic (ROC) analysis was performed. Results: A combined panel of arylsulfatase, hexosaminidase, and COX-2 improved the diagnosis of FSGS by 76%. Hexosaminidase was correlated with the level of proteinuria, while COX-2 was correlated with interstitial inflammation and serum creatinine level in the disease group. Conclusion: Our data supported the implication of these target genes and pathways in the pathogenesis of FSGS. In addition, these genes can be considered as non-invasive biomarkers for FSGS.

scholarly journals Novel mutation in the gonadotropin-releasing hormone receptor (GNRHR) gene in a patient with normosmic isolated hypogonadotropic hypogonadism

2012 ◽  
Vol 56 (8) ◽  
pp. 540-544 ◽  
Author(s):  
Daiane Beneduzzi ◽  
Ericka B. Trarbach ◽  
Ana Claudia Latronico ◽  
Berenice Bilharinho de Mendonca ◽  
Letícia F. G. Silveira
Keyword(s):  
In Silico ◽  
Novel Mutation ◽  
Hypogonadotropic Hypogonadism ◽  
In Silico Analysis ◽  
Control Group ◽  
Coding Region ◽  
Novel Variant ◽  
Gonadotropin Releasing Hormone Receptor ◽  
Inactivating Mutation ◽  
Silico Analysis

We report a novel GNRHR mutation in a male with normosmic isolated hypogonadotropic hypogonadism (nIHH). The coding region of the GNRHR gene was amplified and sequenced. Three variants p.[Asn10Lys;Gln11Lys]; [Tyr283His] were identified in the GNRHR coding region in a male with sporadic complete nIHH. The three variants were absent in the controls (130 normal adults). Familial segregation showed that the previously described p.Asn10Lys and p.Gln11Lys are in the same allele, in compound heterozygozity with the novel variant p.Tyr283His. The p.[Asn10Lys;Gln11Lys] are known inactivating mutations. The p.Tyr283His affects a well-conserved residue, and in silico analysis suggested it is a deleterious variant. We describe a novel GNRHR mutation in a male with nIHH. Absence of the mutation in the control group, conservation among species, in silico analysis, and familial segregation suggest that p.Tyr283His, which was identified in compound heterozygozity with the p.[Asn10Lys;Gln11Lys] variants, is an inactivating mutation. Arq Bras Endocrinol Metab. 2012;56(8):540-4

scholarly journals Transforming Growth Factor Beta has Dual Effects on MMP9 and uPA Expression in HTR-8/SVneo Human Trophoblastic Cell Line

2019 ◽  
Vol 24 (1) ◽  
pp. 26-37
Author(s):  
Sandra Susana Novoa Herran ◽  
Mariela Castelblanco ◽  
Myriam Sanchez-Gomez ◽  
Adriana Umaña Pérez
Keyword(s):  
Transcription Factors ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
In Silico ◽  
Transforming Growth Factor ◽  
In Silico Analysis ◽  
Negative Regulator ◽  
Trophoblast Invasion ◽  
Trophoblastic Cell ◽  
Growth Factor Beta

Invasion of trophoblast into endometrium is vital for successful pregnancy development. MMP9 and uPA are key proteases in this process, but it is still not clear the regulation of its expression by Transforming Growth Factor Beta (TGF-β), known negative regulator of trophoblast invasion. We evaluated the effect of TGF-β on the transcriptional expression of uPA and MMP9 over time, in HTR- /SVneo trophoblast cells cultured with or without 0.5 % fetal bovine serum, via RT qPCR. The involved transcription factors and signaling pathways were analyzed in silico, using Proscan, Enrich, PCViz and WikiPathway. Results showed that that TGF-β regulates the expression of uPA and MMP9. Serum modified the nature of TGF-β’s effects on uPA expression, from negative without serum to positive with it, showing opposite effects on MMP9 expression. In silico analysis evidenced different transcription factors for each protease, some belonging to TGF-β ssignaling pathway, and crosstalk with MAPK and Wnt/β-catenin pathways. The TGF-β ddual role is discussed proposing that serum affects the cellular context. Transcriptional regulation of MMP9 and uPA by TGF-β is differential and depends on serum presence and evaluation time.

scholarly journals A clinical and in-silico analysis of hsa-miR-21 and Growth Differentiation factor-15 expression in Diabetic Nephropathy

2021 ◽  
Author(s):  
Riddhi Girdhar Agarwal ◽  
Purvi Purohit ◽  
Manoj Khokhar ◽  
Anupama Modi ◽  
Nitin Kumar Bajpai ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Transcription Factors ◽  
In Silico ◽  
Clinical Chemistry ◽  
In Silico Analysis ◽  
Healthy Controls ◽  
Ppi Network ◽  
Renal Disorder ◽  
Stage Renal Disease ◽  
Silico Analysis

Abstract Background: Diabetic Nephropathy (DN), a microvascular complication, is a major cause of end-stage renal disease (ESRD). GDF-15 and hsa-miR-21 are closely associated with endothelial dysfunction and inflammation.Methods: In-silico analysis was used to identify GDF-15 and insulin related protein-protein interaction (PPI) network and a common set of GDF-15 regulating transcription factors. Common targeting miRNA of GDF-15 regulating transcription factors were investigated in miRNet and TargetScan. Further, 30 type 2 DN patients and 30 healthy controls were included for clinical chemistry analysis, to analyze serum GDF-15 levels by ELISA and to evaluate the fold change expression (FCE) of circulating hsa-miR-21 by RT-PCR.Results: In the PPI network of IRS1, IRS2, INSR, IGF1R, INS, AKT1, PPARG, CEBPB, EGR1, TP53, KLF4, ATF3, GDF15, TWIST2, the common nodes between insulin and GDF-15 were identified. MicroRNA-21 was bioinformatically observed to directly target GDF-15 downregulating transcription factors KLF4, TP-53, and CEBPB. Serum GDF-15 was nearly ten (10) folds higher in DN patients (p˂0.0001) as compared to healthy controls. A positive and significant correlation of serum GDF-15 was found with HbA1c, HOMA-IR, serum urea and serum creatinine. The FCE of hsa-miR-21 was 9.18 folds higher in DN patients. Conclusion: Raised serum GDF-15 and circulating hsa-miR-21 can serve as clinically important therapeutic targets and biomarkers of progressive renal disorder.

Sign in / Sign up

Export Citation Format

Share Document