160. THE POTENTIAL ROLE OF microRNAs IN THE DEVELOPMENT OF THE HUMAN PLACENTA IN EARLY PREGNANCY

2009 ◽  
Vol 21 (9) ◽  
pp. 78
Author(s):  
W. Kong ◽  
R. Nowak ◽  
C. T. Roberts ◽  
J. A. Owens
Keyword(s):  
Gene Expression ◽  
Transcriptional Repression ◽  
Regulatory Networks ◽  
Mirna Gene ◽  
Differentially Expressed ◽  
Molecular Networks ◽  
Placental Development ◽  
Altered Expression ◽  
Differentially Expressed Mirnas ◽  
Pathways Analysis

Placental functional development is characterised by dynamic and co-ordinated changes in expression of genes that drive invasion, differentiation and growth. These changes may arise in part from altered expression of microRNAs (miRNAs) via their regulatory networks. MiRNAs are short, single-stranded, non-coding RNAs involved in the post-transcriptional repression of gene expression. MiRNAs bind to complementary sites in the 3'UTR of target mRNAs to repress or silence translation. MiRNAs have been detected in the mammalian placenta, but their patterns of expression throughout pregnancy have not been systematically characterized. Using microarrays, miRNA gene expression was compared at two stages (6–8 weeks, 10–12 weeks) in early gestation, in chorionic villi of human placentas (term ~40 weeks). Putative and validated targets of differentially expressed miRNAs were extracted from freely accessible databases, miRBase [1], PicTar [2], TargetScan [3] and miRecords [4]. 15 miRNAs were differentially expressed between these gestational ages (p<0.05). 11 of these miRNAs were upregulated in 10–12 week villi and 4 were downregulated. Many of the differentially expressed miRNAs are members of the same polycistronic clusters, suggesting that these miRNAs may be co-expressed. Shared targets of differentially expressed miRNAs from the same clusters were assessed using Ingenuity Pathways Analysis, to search for significantly represented molecular networks. All downregulated miRNAs at 10–12 weeks shared 35 putative targets and fell into 1 of 2 clusters, on chromosome 13 or X. Previously validated targets include PTEN [5], Notch1 [6], VEGFA [7], CDKN2A [8] and DHFR [9] . Six of the upregulated miRNAs at 10–12 weeks are members of 3 clusters on chromosome 19, 9 and X. Networks targeted by these cluster members include PTEN, HIF1α and IL-12 signalling. Together all of these processes are active and important in early placentation and their predicted targeting by differentially expressed miRNAs is consistent with an important role in placental development.

scholarly journals Circulating MicroRNA Profiles Differ between Hyperglycemia and Euglycemia in Coronary Heart Disease Patients

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Yunyao Jiang ◽  
Nan Liu ◽  
Bingjie Xue ◽  
Jincai Hou ◽  
Chengren Lin ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Regulatory Networks ◽  
Rna Binding ◽  
Mirna Gene ◽  
Differentially Expressed ◽  
Circulating Microrna ◽  
Increased Risk ◽  
Differentially Expressed Mirnas ◽  
Cellular Components

Coronary heart disease (CHD) has become one of the leading causes of death and functional impairment in the world. Hyperglycemia is associated with an increased risk of cardiovascular disease. It was speculated that miRNAs in peripheral blood were a primary parameter in discriminating CHD. The biological characteristics of coronary heart disease with hyperglycemia (HCHD) and coronary heart disease with euglycemia (ECHD) were investigated in the study. Circulating miRNAs from 26 HCHD patients and 42 ECHD patients were identified by microarrays. Compared with the healthy patients, 15 and 20 differentially expressed miRNAs were identified in HCHD and ECHD groups, respectively. Gene ontology analysis was carried out by DAVID and functional annotations of the miRNA targets related to ATP binding, cellular components, protein binding, RNA binding, DNA binding, and so on. KEGG database was used for pathway analysis. Eleven pathways were identified in both HCHD and ECHD groups. Furthermore, 13 and 3 pathways were only identified in HCHD or ECHD group, respectively. And then, miRNA-gene regulatory networks were constructed to study the relationship between differentially expressed miRNAs and genes. This suggested that hsa-let-7c-5p and hsa-miR-24-3p might have the most important function for hyperglycemia in coronary heart disease patients.

scholarly journals MicroRNA (miRNA) Expression is Regulated by Butyrate-Induced Epigenetic Modulation of Gene Expression in Bovine Cells

2010 ◽  
Vol 3 ◽  
pp. GEG.S6144 ◽  
Author(s):  
Cong-Jun Li ◽  
Robert W. Li ◽  
Theodore H. Elsasser
Keyword(s):  
Gene Expression ◽  
Histone Acetylation ◽  
Mirna Expression ◽  
Gene Networks ◽  
Differentially Expressed ◽  
Cellular Functions ◽  
Differentially Expressed Mirnas ◽  
Pathways Analysis ◽  
Modulation Of Gene Expression ◽  
Epigenetic Modulation

We present evidence that butyrate induced histone acetylation regulates miRNA expression. MicroRNA expression microarray profiling revealed that 35 miRNA transcripts are significantly ( P < 0.05) differentially expressed after cells were treated with 10 mM butyrate. Among them, 11 transcripts are differentially expressed very significantly ( P < 0.01). The functional and pathways analysis using MetaCore analytical suite shows differentially expressed miRNAs targeting some very important gene networks and differentially expressed miRNAs may interfere with butyrate induced modulation of gene expression and cellular functions. The data indicates the complicated interaction between miRNA and histone acetylation forms a highly integrated regulatory mechanism.

scholarly journals X chromosome-dependent disruption of placental regulatory networks in hybrid dwarf hamsters

Genetics ◽  
2021 ◽  
Author(s):  
Thomas D Brekke ◽  
Emily C Moore ◽  
Shane C Campbell-Staton ◽  
Colin M Callahan ◽  
Zachary A Cheviron ◽  
...  
Keyword(s):  
Gene Expression ◽  
X Chromosome ◽  
Regulatory Networks ◽  
Mammalian Species ◽  
Strongly Correlated ◽  
Placental Development ◽  
Substitution Lines ◽  
Genome Wide ◽  
Highly Sensitive ◽  
First And Second Generation

AbstractEmbryonic development in mammals is highly sensitive to changes in gene expression within the placenta. The placenta is also highly enriched for genes showing parent-of-origin or imprinted expression, which is predicted to evolve rapidly in response to parental conflict. However, little is known about the evolution of placental gene expression, or if divergence of placental gene expression plays an important role in mammalian speciation. We used crosses between two species of dwarf hamsters (Phodopus sungorus and Phodopus campbelli) to examine the genetic and regulatory underpinnings of severe placental overgrowth in their hybrids. Using quantitative genetic mapping and mitochondrial substitution lines, we show that overgrowth of hybrid placentas was primarily caused by genetic differences on the maternally inherited P. sungorus X chromosome. Mitochondrial interactions did not contribute to abnormal hybrid placental development, and there was only weak correspondence between placental disruption and embryonic growth. Genome-wide analyses of placental transcriptomes from the parental species and first- and second-generation hybrids revealed a central group of co-expressed X-linked and autosomal genes that were highly enriched for maternally biased expression. Expression of this gene network was strongly correlated with placental size and showed widespread misexpression dependent on epistatic interactions with X-linked hybrid incompatibilities. Collectively, our results indicate that the X chromosome is likely to play a prominent role in the evolution of placental gene expression and the accumulation of hybrid developmental barriers between mammalian species.

scholarly journals Genome-Wide microRNA Profiling Using Oligonucleotide Microarray Reveals Regulatory Networks of microRNAs in Nicotiana benthamiana During Beet Necrotic Yellow Vein Virus Infection

Viruses ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 310 ◽  
Author(s):  
Junying Liu ◽  
Huiyan Fan ◽  
Ying Wang ◽  
Chenggui Han ◽  
Xianbing Wang ◽  
...  
Keyword(s):  
Nicotiana Benthamiana ◽  
Regulatory Networks ◽  
Target Genes ◽  
Tobacco Rattle Virus ◽  
Yellow Vein ◽  
Differentially Expressed ◽  
Virus Induced Gene Silencing ◽  
Developmental Defects ◽  
Differentially Expressed Mirnas ◽  
Species Specific

Beet necrotic yellow vein virus (BNYVV) infections induce stunting and leaf curling, as well as root and floral developmental defects and leaf senescence in Nicotiana benthamiana. A microarray analysis with probes capable of detecting 1596 candidate microRNAs (miRNAs) was conducted to investigate differentially expressed miRNAs and their targets upon BNYVV infection of N. benthamiana plants. Eight species-specific miRNAs of N. benthamiana were identified. Comprehensive characterization of the N. benthamiana microRNA profile in response to the BNYVV infection revealed that 129 miRNAs were altered, including four species-specific miRNAs. The targets of the differentially expressed miRNAs were predicted accordingly. The expressions of miR164, 160, and 393 were up-regulated by BNYVV infection, and those of their target genes, NAC21/22, ARF17/18, and TIR, were down-regulated. GRF1, which is a target of miR396, was also down-regulated. Further genetic analysis of GRF1, by Tobacco rattle virus-induced gene silencing, assay confirmed the involvement of GRF1 in the symptom development during BNYVV infection. BNYVV infection also induced the up-regulation of miR168 and miR398. The miR398 was predicted to target umecyanin, and silencing of umecyanin could enhance plant resistance against viruses, suggesting the activation of primary defense response to BNYVV infection in N. benthamiana. These results provide a global profile of miRNA changes induced by BNYVV infection and enhance our understanding of the mechanisms underlying BNYVV pathogenesis.

scholarly journals Construction of miRNA-target networks using microRNA profiles of CVB3-infected HeLa cells

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Hai Lan Yao ◽  
Mi Liu ◽  
Wen Jun Wang ◽  
Xin Ling Wang ◽  
Juan Song ◽  
...  
Keyword(s):  
Hela Cells ◽  
Regulatory Networks ◽  
Cellular Differentiation ◽  
High Throughput Sequencing ◽  
Target Genes ◽  
Expression Profiles ◽  
Differentially Expressed ◽  
Mirna Regulation ◽  
Cvb3 Infection ◽  
Differentially Expressed Mirnas

AbstractMicroRNAs (miRNAs) play an important role in regulating gene expression in multiple biological processes and diseases. Thus, to understand changes in miRNA during CVB3 infection, specific miRNA expression profiles were investigated at 3 h, 6 h, and 9 h postinfection in HeLa cells by small-RNA high-throughput sequencing. Biological implications of 68 differentially expressed miRNAs were analyzed through GO and KEGG pathways. Interaction networks between 34 known highly differentially expressed miRNAs and targets were constructed by mirDIP and Navigator. The predicted targets showed that FAM135A, IKZF2, PLAG1, ZNF148, PHC3, LCOR and DYRK1A, which are associated with cellular differentiation and transcriptional regulation, were recognized by 8 miRNAs or 9 miRNAs through interactional regulatory networks. Seven target genes were confirmed by RT-qPCR. The results showed that the expression of DYRK1A, FAM135A, PLAG1, ZNF148, and PHC3 were obviously inhibited at 3 h, 6 h, and 9 h postinfection. The expression of LCOR did not show a significant change, and the expression of IKZF2 increased gradually with prolonged infection time. Our findings improve the understanding of the pathogenic mechanism of CVB3 infection on cellular differentiation and development through miRNA regulation, which has implications for interventional approaches to CVB3-infection therapy. Our results also provide a new method for screening target genes of microRNA regulation in virus-infected cells.

scholarly journals Role of miRNAs in Sigmoid Colon Cancer: A Search for Potential Biomarkers

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3311
Author(s):  
Diego Marques ◽  
Layse Raynara Ferreira-Costa ◽  
Lorenna Larissa Ferreira-Costa ◽  
Ana Beatriz Bezerra-Oliveira ◽  
Romualdo da Silva Correa ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Sigmoid Colon ◽  
Cancer Progression ◽  
Target Genes ◽  
Mirna Gene ◽  
Differentially Expressed ◽  
Sigmoid Colon Cancer ◽  
Colon Tissue ◽  
Aberrant Expression ◽  
Differentially Expressed Mirnas

The aberrant expression of microRNAs in known to play a crucial role in carcinogenesis. Here, we evaluated the miRNA expression profile of sigmoid colon cancer (SCC) compared to adjacent-to-tumor (ADJ) and sigmoid colon healthy (SCH) tissues obtained from colon biopsy extracted from Brazilian patients. Comparisons were performed between each group separately, considering as significant p-values < 0.05 and |Log2(Fold-Change)| > 2. We found 20 differentially expressed miRNAs (DEmiRNAs) in all comparisons, two of which were shared between SCC vs. ADJ and SCC vs. SCH. We used miRTarBase, and miRTargetLink to identify target-genes of the differentially expressed miRNAs, and DAVID and REACTOME databases for gene enrichment analysis. We also used TCGA and GTEx databases to build miRNA-gene regulatory networks and check for the reproducibility in our results. As findings, in addition to previously known miRNAs associated with colorectal cancer, we identified three potential novel biomarkers. We showed that the three types of colon tissue could be clearly distinguished using a panel composed by the 20 DEmiRNAs. Additionally, we found enriched pathways related to the carcinogenic process in which miRNA could be involved, indicating that adjacent-to-tumor tissues may be already altered and cannot be considered as healthy tissues. Overall, we expect that these findings may help in the search for biomarkers to prevent cancer progression or, at least, allow its early detection, however, more studies are needed to confirm our results.

MODELING NONLINEAR GENE REGULATORY NETWORKS FROM TIME SERIES GENE EXPRESSION DATA

2008 ◽  
Vol 06 (05) ◽  
pp. 961-979 ◽  
Author(s):  
ANDRÉ FUJITA ◽  
JOÃO RICARDO SATO ◽  
HUMBERTO MIGUEL GARAY-MALPARTIDA ◽  
MARI CLEIDE SOGAYAR ◽  
CARLOS EDUARDO FERREIRA ◽  
...  
Keyword(s):  
Gene Expression ◽  
Time Series ◽  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
Expression Profiles ◽  
A Priori ◽  
Molecular Networks ◽  
Biological Knowledge ◽  
Vector Autoregressive ◽  
Gene Regulatory

In cells, molecular networks such as gene regulatory networks are the basis of biological complexity. Therefore, gene regulatory networks have become the core of research in systems biology. Understanding the processes underlying the several extracellular regulators, signal transduction, protein–protein interactions, and differential gene expression processes requires detailed molecular description of the protein and gene networks involved. To understand better these complex molecular networks and to infer new regulatory associations, we propose a statistical method based on vector autoregressive models and Granger causality to estimate nonlinear gene regulatory networks from time series microarray data. Most of the models available in the literature assume linearity in the inference of gene connections; moreover, these models do not infer directionality in these connections. Thus, a priori biological knowledge is required. However, in pathological cases, no a priori biological information is available. To overcome these problems, we present the nonlinear vector autoregressive (NVAR) model. We have applied the NVAR model to estimate nonlinear gene regulatory networks based entirely on gene expression profiles obtained from DNA microarray experiments. We show the results obtained by NVAR through several simulations and by the construction of three actual gene regulatory networks (p53, NF-κB, and c-Myc) for HeLa cells.

Molecular Background of BCP-ALL Cases with an Early Switch to Monocytic Lineage

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3562-3562
Author(s):  
Karel Fišer ◽  
Lucie Slámová ◽  
Alena Dobiášová ◽  
Júlia Starková ◽  
Eva Froňková ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Transcription Factors ◽  
B Cell ◽  
Differentially Expressed ◽  
Lineage Commitment ◽  
Altered Expression ◽  
B Lineage ◽  
And Control ◽  
Monocytic Lineage

Abstract We identified a subset of BCP-ALL with switch towards the monocytic lineage within the first month of treatment (swALL)[Slámová et al Leukemia 2014]. During the switch cells gradually lose CD19 and CD34 expression and acquire CD33 and CD14 positivity. We proved clonal relatedness of switched monocytic blasts with the diagnostic leukemic cells based on identical Ig-TCR rearrangements. SwALL cases are not associated with MLL or BCR/ABL1 aberrancies and lack any known genetic markers of lineage ambiguity (detected by FISH or MLPA). We analyzed transcriptomes of swALL samples at diagnosis (n=4) and at d8 (n=4) where the immunophenotypic switching was already apparent as well as control BCP-ALL (n=4). RNA was isolated form either FACS sorted cells or whole BM when blasts constituted >80% of cells. For RNA-Seq we used Illumina HiSeq 2000 paired-end or single end sequencing. Raw sequencing data were analyzed using adapted protocol from Anders at al [Anders et al Nature Protocols 2013] and custom scripts. For methylome analysis we used Enhanced Reduced Representation Bisulfite Sequencing (ERRBS)[Akalin et al PLoS Genetics 2012]. ERRBS quantitatively measures DNA methylation at ~3M CpGs genome-wide. Samples from swALL at diagnosis (n=7) and at d8 (n=4) and control BCP-ALL (n=4) were processed. Analysis was performed according to [Akalin et al Genome Biology 2012] and followed with custom analysis in R statistical language. Comparison (generalized exact binomial test) of transcriptomes of B-lineage blasts from diagnosis between swALLs and control BCP-ALLs revealed a number of differentially expressed genes. Among 300 most significantly differentially expressed were KLF4, CEBPD, CLEC12A and CLEC12B (upregulated in swALL) and ANXA5, VPREB1, CD9 and IGHG3 (downregulated in swALL). Hierarchical clustering separated not only swALL and control BCP-ALL, but also swALL cells before and during the monocytic switch. Changes in gene expression during lineage switch included downregulation of ITGA6, Id2, EBF1, CD19, CD34, FLT3, MYB, CD79a, BCR, PAX5, GATA3 and TCF3 genes and upregulation of S100A10, AIF1, CD14, CD33, LGALS1, RNF130 and MNDA. When comparing all three cell types (swALL B cell and monocytic blasts and control BCP-ALL blasts) we concentrated on 1) immunophenotype switch markers and 2) lineage related transcription factors (TF): 1) Both markers typical for B cell blasts (CD19, CD34) decreased during the switch. However while CD19 was expressed in swALL at diagnosis at same levels as in control BCP-ALL, CD34 was overexpressed in swALL compared to BCP-ALL at diagnosis. Both monocytic markers (CD33, CD14) increased their expression during the switch. CD14 showed no difference between swALL and control BCP-ALL at diagnosis. However CD33 was interestingly upregulated in swALL already at diagnosis and continued to rise during the switch. SwALL had therefore deregulated expression of lineage commitment markers already at diagnosis favoring stemness marker CD34 and myeloid marker CD33. 2) B lineage commitment related TFs (EBF1, TCF3, PAX5) were expressed in B lineage blasts in both swALL and control BCP-ALL. However they were all downregulated during the switch. On the other hand myeloid lineage related transcription factor CEBPA is overexpressed in diagnostic B lineage blasts in swALL compared to control BCP-ALL cases. Similarly CEBPD is overexpressed in swALL and its expression further rises during the switch. Other hematopoietic TFs upregulated in swALL cases include KLF4, NANOG and GATA3. To confirm some of the epigenetic markers of swALL cases (demethylation of CEBPA promoter) and to widen epigenetic screening we used ERRBS. While some of the upregulated genes had expectedly hypomethylated promoters in swALL (CEBPA, GATA3) other genes (TCF3, PAX5) had demethylated promoters in all cases. While the whole DNA methylation picture is still a challenge to draw both omics method could clearly separate swALL cases from control BCP-ALL using principal component analysis. In summary we show that immunophenotypic shift is associated with gene expression changes of surface markers, lineage specific transcription factors and other genes. Some of the genes have altered expression already at diagnosis. Expression of some key lineage genes is differentially regulated by DNA methylation. Supported by: GAUK 914613, GAČR P301/10/1877, UNCE 204012, IGA NT13462-4 Disclosures No relevant conflicts of interest to declare.

scholarly journals Gene expression profiling in whole blood of patients with coronary artery disease

2010 ◽  
Vol 119 (8) ◽  
pp. 335-343 ◽  
Author(s):  
Chiara Taurino ◽  
William H. Miller ◽  
Martin W. McBride ◽  
John D. McClure ◽  
Raya Khanin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Gene Expression Profiling ◽  
Whole Blood ◽  
Expression Profiling ◽  
Gene Expression Analysis ◽  
Differentially Expressed ◽  
Differentially Expressed Mirnas ◽  
Artery Disease

Owing to the dynamic nature of the transcriptome, gene expression profiling is a promising tool for discovery of disease-related genes and biological pathways. In the present study, we examined gene expression in whole blood of 12 patients with CAD (coronary artery disease) and 12 healthy control subjects. Furthermore, ten patients with CAD underwent whole-blood gene expression analysis before and after the completion of a cardiac rehabilitation programme following surgical coronary revascularization. mRNA and miRNA (microRNA) were isolated for expression profiling. Gene expression analysis identified 365 differentially expressed genes in patients with CAD compared with healthy controls (175 up- and 190 down-regulated in CAD), and 645 in CAD rehabilitation patients (196 up- and 449 down-regulated post-rehabilitation). Biological pathway analysis identified a number of canonical pathways, including oxidative phosphorylation and mitochondrial function, as being significantly and consistently modulated across the groups. Analysis of miRNA expression revealed a number of differentially expressed miRNAs, including hsa-miR-140-3p (control compared with CAD, P=0.017), hsa-miR-182 (control compared with CAD, P=0.093), hsa-miR-92a and hsa-miR-92b (post- compared with pre-exercise, P<0.01). Global analysis of predicted miRNA targets found significantly reduced expression of genes with target regions compared with those without: hsa-miR-140-3p (P=0.002), hsa-miR-182 (P=0.001), hsa-miR-92a and hsa-miR-92b (P=2.2×10−16). In conclusion, using whole blood as a ‘surrogate tissue’ in patients with CAD, we have identified differentially expressed miRNAs, differentially regulated genes and modulated pathways which warrant further investigation in the setting of cardiovascular function. This approach may represent a novel non-invasive strategy to unravel potentially modifiable pathways and possible therapeutic targets in cardiovascular disease.

scholarly journals СONSECUTIVE INTEGRATION OF AVAILABLE MICROARRAY DATA FOR ANALYSIS OF DIFFERENTIAL GENE EXPRESSION IN HUMAN PLACENTA

2021 ◽  
Vol 14 (1) ◽  
pp. 38-45
Author(s):  
O. Lykhenko ◽  
Keyword(s):  
Gene Expression ◽  
Differential Gene Expression ◽  
Differentially Expressed Genes ◽  
Human Placenta ◽  
Normal Pregnancy ◽  
Integrative Analysis ◽  
Differentially Expressed ◽  
Second Trimester ◽  
Placental Development ◽  
Differential Gene

The purpose of the study was to provide the pipeline for processing of publicly available unprocessed data on gene expression via integration and differential gene expression analysis. Data collection from open gene expression databases, normalization and integration into a single expression matrix in accordance with metadata and determination of differentially expressed genes were fulfilled. To demonstrate all stages of data processing and integrative analysis, there were used the data from gene expression in the human placenta from the first and second trimesters of normal pregnancy. The source code for the integrative analysis was written in the R programming language and publicly available as a repository on GitHub. Four clusters of functionally enriched differentially expressed genes were identified for the human placenta in the interval between the first and second trimester of pregnancy. Immune processes, developmental processes, vasculogenesis and angiogenesis, signaling and the processes associated with zinc ions varied in the considered interval between the first and second trimester of placental development. The proposed sequence of actions for integrative analysis could be applied to any data obtained by microarray technology.

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