scholarly journals Identification of Transcriptional Markers and microRNA–mRNA Regulatory Networks in Colon Cancer by Integrative Analysis of mRNA and microRNA Expression Profiles in Colon Tumor Stroma

Cells ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 1054 ◽  
Author(s):  
Md. Nazim Uddin ◽  
Mengyuan Li ◽  
Xiaosheng Wang
Keyword(s):  
Colon Cancer ◽  
Mirna Expression ◽  
Expression Profiling ◽  
Regulatory Networks ◽  
Tumor Stroma ◽  
Receptor Interaction ◽  
Colon Tumor ◽  
Ppi Network ◽  
Hub Genes ◽  
Mirna Expression Profiling

The aberrant expression of microRNAs (miRNAs) and genes in tumor microenvironment (TME) has been associated with the pathogenesis of colon cancer. An integrative exploration of transcriptional markers (gene signatures) and miRNA–mRNA regulatory networks in colon tumor stroma (CTS) remains lacking. Using two datasets of mRNA and miRNA expression profiling in CTS, we identified differentially expressed miRNAs (DEmiRs) and differentially expressed genes (DEGs) between CTS and normal stroma. Furthermore, we identified the transcriptional markers which were both gene targets of DEmiRs and hub genes in the protein–protein interaction (PPI) network of DEGs. Moreover, we investigated the associations between the transcriptional markers and tumor immunity in colon cancer. We identified 17 upregulated and seven downregulated DEmiRs in CTS relative to normal stroma based on a miRNA expression profiling dataset. Pathway analysis revealed that the downregulated DEmiRs were significantly involved in 25 KEGG pathways (such as TGF-β, Wnt, cell adhesion molecules, and cytokine–cytokine receptor interaction), and the upregulated DEmiRs were involved in 10 pathways (such as extracellular matrix (ECM)-receptor interaction and proteoglycans in cancer). Moreover, we identified 460 DEGs in CTS versus normal stroma by a meta-analysis of two gene expression profiling datasets. Among them, eight upregulated DEGs were both hub genes in the PPI network of DEGs and target genes of the downregulated DEmiRs. We found that three of the eight DEGs were negative prognostic factors consistently in two colon cancer cohorts, including COL5A2, EDNRA, and OLR1. The identification of transcriptional markers and miRNA–mRNA regulatory networks in CTS may provide insights into the mechanism of tumor immune microenvironment regulation in colon cancer.

scholarly journals Genome-wide mRNA and miRNA expression profiling reveal multiple regulatory networks in colorectal cancer

2015 ◽  
Vol 6 (1) ◽  
pp. e1614-e1614 ◽  
Author(s):  
R Vishnubalaji ◽  
R Hamam ◽  
M-H Abdulla ◽  
M A V Mohammed ◽  
M Kassem ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Mirna Expression ◽  
Expression Profiling ◽  
Regulatory Networks ◽  
Genome Wide ◽  
Mirna Expression Profiling

scholarly journals Serum microRNA Expression Profiling in Malaria Patients and Bioinformatic Analysis of Hsa-miR-106b-5p

2021 ◽  
Author(s):  
Jiacong Peng ◽  
Xiaohong Peng ◽  
Ying Wang ◽  
Liping Jiang ◽  
Dayu Li ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Mirna Expression ◽  
Expression Profiling ◽  
Target Genes ◽  
Small Gtpase ◽  
Differentially Expressed ◽  
Ppi Network ◽  
Kegg Analysis ◽  
Significant Difference ◽  
Mirna Expression Profiling

Abstract BackgroundMalaria, caused by Plasmodium, is one of the three major infectious diseases that se­riously endangers public health. Resistance to an­ti-malarial drugs and insecticides has made the prevention and control of malar­ia shown little improvement in the last four years. This study aimed to explore the changes in microRNA (miRNA) expression profiling of malaria patient and predict malaria-related miRNA by bioinformatics methods to provide theoretical basis for further verification of the correlation between specific miRNAs and immune regulation of malaria.MethodsSerum of patients infected by Plasmodium falciparum and healthy people from Myanmar border area was collected. miRNA expression profiling was obtained by RT-qPCR. Then the differentially expressed miRNA was screened and target genes were predicted by four miRNA databases (TargetScan, DIANA-microT, miRDB, and miRTarbase) and an intersection of target genes was obtained by Venn analysis. GO and KEGG analysis were performed for the overlapping target genes via Metascape. The results were further visualized by Cytoscape. Finally, Protein-protein interaction (PPI) network of predicted overlapping target genes was built by STRING.ResultsAmong the 341 tested serum miRNAs, 64 were differentially expressed in malaria patients (P<0.05), 27 miRNAs were up-regulated and 37 miRNAs were down-regulated. The miRNA with the most significant difference was hsa-miR-106b-5p (FC=14.871, adjusted.P.value<0.01); GO and KEGG analysis found that its overlapping predicted target gene set was remarkably enriched in biological functions such as GO:0007264~small GTPase mediated signal transduction, GO:0051056~regulation of small GTPase mediated signal transduction, GO:0051020~GTPase binding, GO:0048514~blood vessel morphogenesis(P<0.01) and signal pathway such as hsa04144: Endocytosis, hsa01521:EGFR tyrosine kinase inhibitor resistance, hsa05212:Pancreatic cancer (P<0.01); Besides, a PPI network containing 39 predicted target genes of hsa-miR-106b-5p was constructed, and 5 hub genes VEGFA, STAT3, RACGAP1, OCRL, and RBBP7 have been selected.ConclusionThe bioinformatics analysis results indicated that hsa-miR-106b-5p has a great relationship with malaria, it plays a part in inhibiting the emergence of ARTs resistance in Plasmodium and tumor progression, which may be achieved by regulating vascular morphogenesis, endocytosis, and VEGFA. The underlying mechanism needs to be further elucidated. We believe that this finding will facilitate an in-depth research on the as­sociation between malaria and miRNA.

scholarly journals Genome-wide miRNA expression profiling in potato (Solanum tuberosum L.) reveals TOR-dependent post-transcriptional gene regulatory networks in diverse metabolic pathway

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e10704
Author(s):  
Kexuan Deng ◽  
Huan Yin ◽  
Fangjie Xiong ◽  
Li Feng ◽  
Pan Dong ◽  
...  
Keyword(s):  
Gene Regulatory Networks ◽  
Mirna Expression ◽  
Expression Profiling ◽  
Regulatory Networks ◽  
Large Scale ◽  
Solanum Tuberosum L ◽  
Transcriptional Level ◽  
Promote Cell Proliferation ◽  
Gene Regulatory ◽  
Mirna Expression Profiling

Target of rapamycin (TOR) operates as a hub of the signal transduction that integrates nutrient and energy signaling to promote cell proliferation and growth through mediating the transcriptional and post- transcriptional regulator networks in all eukaryotic species. MicroRNAs (miRNAs) are widespread classes of small, single-stranded, non-coding endogenous RNAs and are widely found in eukaryotes, which play a vital role in regulating gene expression by degrading targeted mRNAs or translational repression at post-transcriptional level. Recent studies found that there were necessarily close connections between miRNA and TOR pathways in mammals. However, there is little information about the interplay between the miRNA and TOR in plants. Thus, the aim of this study was to identify potential TOR-miRNA-mRNA regulatory networks in TOR signaling through global mRNA and microRNA expression profiling in potato. Based on the previous high-throughput transcriptome sequencing and filtering, a total of 2,899 genes were significantly differentially expressed in potato under TOR inhibitors treatment. Pathway analysis revealed that these genes were significantly enriched in multiple metabolic processes. Similarly, in the present study, suppression of TOR resulted in 41 miRNAs up-regulated and 45 down-regulated, revealing that TOR plays a crucial role in the regulation of miRNA regulatory network. Furthermore, integrated mRNA and miRNA expression profiling uncovered that these miRNAs participated in large-scale metabolic process in the TOR signal pathway in potato, such as regulation of autophagy and ubiquitination, and biosynthesis of secondary metabolites. Overall, the results shed new insight into TOR related post-transcriptional gene regulatory networks in potato and suggesting TOR-miRNA-targeting genes relevant networks as a potential genetic resource for potato improvement.

scholarly journals Identification of hub genes in colon cancer via bioinformatics analysis

2020 ◽  
Vol 48 (9) ◽  
pp. 030006052095323
Author(s):  
Jun Liu ◽  
Gui-Li Sun ◽  
Shang-Ling Pan ◽  
Meng-Bin Qin ◽  
Rong Ouyang ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Bioinformatics Analysis ◽  
Expression Profiles ◽  
Organic Anion ◽  
The Cancer Genome Atlas ◽  
Prognostic Indicators ◽  
Venn Diagram ◽  
Receptor Interaction ◽  
Ppi Network ◽  
Hub Genes

Objectives This study aimed to investigate hub genes and their prognostic value in colon cancer via bioinformatics analysis. Methods Differentially expressed genes (DEGs) of expression profiles (GSE33113, GSE20916, and GSE37364) obtained from Gene Expression Omnibus (GEO) were identified using the GEO2R tool and Venn diagram software. Function and pathway enrichment analyses were performed, and a protein–protein interaction (PPI) network was constructed. Hub genes were verified based on The Cancer Genome Atlas (TCGA) and Human Protein Atlas (HPA) databases. Results We identified 207 DEGs, 62 upregulated and 145 downregulated genes, enriched in Gene Ontology terms “organic anion transport,” “extracellular matrix,” and “receptor ligand activity”, and in the Kyoto Encyclopedia of Genes and Genomes pathway “cytokine-cytokine receptor interaction.” The PPI network was constructed and nine hub genes were selected by survival analysis and expression validation. We verified these genes in the TCGA database and selected three potential predictors ( ZG16, TIMP1, and BGN) that met the independent predictive criteria. TIMP1 and BGN were upregulated in patients with a high cancer risk, whereas ZG16 was downregulated. The immunostaining results from HPA supported these findings. Conclusion This study indicates that these hub genes may be promising prognostic indicators or therapeutic targets for colon cancer.

scholarly journals Contribution of endothelial cell-derived transcriptomes to the colon cancer based on bioinformatics analysis

2021 ◽  
Vol 18 (6) ◽  
pp. 7280-7300
Author(s):  
Jie Wang ◽  
◽  
Md. Nazim Uddin ◽  
Rehana Akter ◽  
Yun Wu ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Endothelial Cells ◽  
Bioinformatics Analysis ◽  
Immune Cell ◽  
M2 Macrophage ◽  
Colon Tumor ◽  
Ppi Network ◽  
Hub Genes ◽  
Protein Protein Interaction ◽  
Immunosuppressive Cells

<abstract> <p>Colon tumor endothelial cells (CTECs) plays substantial roles to induce immune invasion, angiogenesis and metastasis. Thus, identification of the CTECs-derived transcriptomes could be helpful for colon cancer diagnosis and potential therapy. </p> <sec><title>Methods</title><p> By analysis of CTECs-derived gene expression profiling dataset, we identified differentially expressed genes (DEGs) between CTECs and colon normal endothelial cells (CNECs). In addition, we identified the significant pathways and protein-protein interaction (PPI) network that was significantly associated with the DEGs. Furthermore, we identified hub genes whose expression was significantly associated with prognosis and immune cell infiltrations in colon cancer. Finally, we identified the significant correlations between the prognostic hub genes and immune-inhibitory markers in colon cancer. </p></sec> <sec><title>Results</title><p>We identified 362 DEGs in CTECs relative to the CNECs, including117 up-regulated genes and 245 down-regulated genes in the CTECs. In addition, we identified significantly up-regulated pathways in CTECs that were mainly involved in cancer and immune regulation. Furthermore, we identified hub genes (such as <italic>SPARC, COL1A1, COL1A2</italic> and <italic>IGFBP3</italic>) that are associated with prognosis and immune cells infiltrations in colon cancer. Interestingly, we found that prognosis-associated hub genes (<italic>SPARC, COL1A1, COL1A2</italic> and <italic>IGFBP3</italic>) are positively correlated with immune-inhibitory markers of various immunosuppressive cells, including TAM, M2 macrophage, Tregs and T cell exhaustion. Finally, our findings revealed that prognosis-associated upregulated hub genes are positively correlated with immune checkpoint markers, including PD-L1 and PD-L2 and the immunosuppressive markers including TGFB1 and TGFBR1.</p></sec> <sec><title>Conclusions</title><p>The identification of CTECs-specific transcriptomes may provide crucial insights into the colon tumor microenvironment that mediates the development of colon cancer.</p></sec> </abstract>

scholarly journals Identification of novel MiRNAs and MiRNA expression profiling during grain development in indica rice

BMC Genomics ◽  
2012 ◽  
Vol 13 (1) ◽  
pp. 264 ◽  
Author(s):  
Ying Lan ◽  
Ning Su ◽  
Yi Shen ◽  
Rongzhi Zhang ◽  
Fuqing Wu ◽  
...  
Keyword(s):  
Mirna Expression ◽  
Expression Profiling ◽  
Indica Rice ◽  
Grain Development ◽  
Mirna Expression Profiling

scholarly journals Identification of Novel Hub Genes Through Expression Profiles Analysis in Adrenocortical Carcinoma

2020 ◽  
Author(s):  
Chenhe Yao ◽  
Xiaoling Zhao ◽  
Xuemeng Shang ◽  
Binghan Jia ◽  
Shuaijie Dou ◽  
...  
Keyword(s):  
Adrenocortical Carcinoma ◽  
Expression Profiling ◽  
Molecular Mechanisms ◽  
Cross Validation ◽  
Expression Profiles ◽  
Ppi Network ◽  
Hub Genes ◽  
Tumor Association ◽  
Prediction Of Prognosis ◽  
Geo Database

Abstract Background: Adrenocortical carcinoma (ACC) is a heterogeneous and rare malignant tumor associated with a poor prognosis. The molecular mechanisms of ACC remain elusive and more accurate biomarkers for the prediction of prognosis are needed.Methods: In this study, integrative profiling analyses were performed to identify novel hub genes in ACC to provide promising targets for future investigation. Three gene expression profiling datasets in the GEO database were used for the identification of overlapped differentially expressed genes (DEGs) following the criteria of adj.P.Value<0.05 and |log2 FC|>0.5 in ACC. Novel hub genes were screened out following a series of processes: the retrieval of DEGs with no known associations with ACC on Pubmed, then the cross-validation of expression values and significant associations with overall survival in the GEPIA2 and starBase databases, and finally the prediction of gene-tumor association in the GeneCards database.Results: Four novel hub genes were identified and two of them, TPX2 and RACGAP1, were positively correlated with the staging. Interestingly, co-expression analysis revealed that the association between TPX2 and RACGAP1 was the strongest and that the expression of HOXA5 was almost completely independent of that of RACGAP1 and TPX2. Furthermore, the PPI network consisting of four novel genes and seed genes in ACC revealed that HOXA5, TPX2, and RACGAP1 were all associated with TP53. Conclusions: This study identified four novel hub genes (TPX2, RACHAP1, HXOA5 and FMO2) that may play crucial roles in the tumorigenesis and the prediction of prognosis of ACC.

scholarly journals Left-Sided Colorectal Cancer Distinct in Indigenous African Patients Compared to Other Ethnic Groups in South Africa.

2021 ◽  
Author(s):  
M. McCabe ◽  
C. Penny ◽  
P. Magangane ◽  
S. Mirza ◽  
Y. Perner
Keyword(s):  
Colorectal Cancer ◽  
South Africa ◽  
Ethnic Groups ◽  
Mirna Expression ◽  
Expression Profiling ◽  
Expression Patterns ◽  
Molecular Characteristics ◽  
Anatomical Site ◽  
Molecular Features ◽  
Mirna Expression Profiling

Abstract Introduction: A large proportion of indigenous African (IA) colorectal cancer (CRC) patients in South Africa are young (<50years), with no unique histopathological or molecular characteristics. Anatomical site as well as microsatellite instability (MSI) status have shown to be associated with different clinicopathological and molecular features. This study aimed to ascertain key histopathological and miRNA expression patterns in microsatellite stable (MSS) and low-frequency MSI (MSI-L) patients, to provide insight into the mechanism of the disease. Methods: A retrospective cohort (2011-2015) of MSS/MSI-L CRC patient samples diagnosed at Charlotte Maxeke Johannesburg Academic Hospital was analyzed. Samples were categorized by site [Right colon cancer (RCC) versus left (LCC)], ethnicity [IA versus other ethnic groups (OEG)] and MSI status (MSI-L vs MSS). T-test, Fischer’s exact and Chi-square tests were conducted. Additional miRNA expression profiling was performed on IA patient samples. Results: IA patients with LCC demonstrated an increased prevalence in males, sigmoid colon, signet-ring-cell morphology, MSI-L with BAT25/26 marker instability and advanced disease association. MiRNA expression profiling revealed unique clustering, with dysregulation of let-7 and miRNA-125. Conclusion: This study revealed distinct histopathological features for LCC, and suggests BAT25/26, miRNAs let-7a-5p and miRNA-125a/b-5p as negative prognostic markers in African CRC patients. Larger confirmatory studies are recommended.

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