scholarly journals Identification of the DNA Replication Regulator MCM Complex Expression and Prognostic Significance in Hepatic Carcinoma

2020 ◽  
Vol 2020 ◽  
pp. 1-18
Author(s):  
Ting Cao ◽  
Shi-jie Yi ◽  
Li-xin Wang ◽  
Juan-xia Zhao ◽  
Jiao Xiao ◽  
...  
Keyword(s):  
Cell Lines ◽  
Prognostic Significance ◽  
Interaction Network ◽  
Normal Liver ◽  
Functional Enrichment ◽  
Hepatic Carcinoma ◽  
Positive Correlation ◽  
Normal Hepatocyte ◽  
Mcm Complex ◽  
High Level

Background. The microliposome maintenance (MCM) complex, MCM2-7, is revealed to be involved in multiple cellular processes and plays a key role in the development and progression of human cancers. However, the MCM complex remains poorly elaborated in hepatic carcinoma (HCC). Methods. In the study, we found the mRNA and protein level by bioinformatics. We also explored the prognostic value, genetic alteration, interaction network, and functional enrichment of MCM2-7. The MCM expression and correlation among these MCMs in HCC cell lines were identified by western blot. Results. MCM2-7 was significantly increased in HCC tissues compared to normal liver tissues. The high level of MCM2-7 had a positive correlation with poor prognosis. However, MCM2-7 alterations were not correlated with poor OS. MCMs were both increased in HCC cell lines compared to the normal hepatocyte cell line. Furthermore, the positive correlation was found among MCMs in HCC cell lines. Conclusions. The MCM complex was increased in HCC tissues and cell lines and negatively correlated with prognosis, which might be important biomarkers for HCC.

scholarly journals Identification of Latent Diagnostic Biomarkers and Biological Pathways in Dermatomyositis Based on WGCNA

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Shaxi Ouyang ◽  
Yifang Liu ◽  
Changjuan Xiao ◽  
Qinghua Zeng ◽  
Xun Luo ◽  
...  
Keyword(s):  
Cell Lines ◽  
Differentially Expressed Gene ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Receptor Interaction ◽  
Interferon Α ◽  
Pathway Enrichment Analysis ◽  
Oligoadenylate Synthetase

Introduction. Dermatomyositis (DM) is a chronic autoimmune disease of predominantly lymphocytic infiltration mainly involving the transverse muscle. Its pathogenesis is remaining unknown. This research is designed to probe the latent pathogenesis of dermatomyositis, identify potential biomarkers, and reveal the pathogenesis of dermatomyositis through information biology analysis of gene chips. Methods. In this study, we utilised the GSE14287 and GSE11971 datasets rooted in the Gene Expression Omnibus (GEO) databank, which included a total of 62 DM samples and 9 normal samples. The datasets were combined, and the differentially expressed gene sets were subjected to weighted gene coexpression network analysis, and the hub gene was screened using a protein interaction network from genes in modules highly correlated with dermatomyositis progression. Results. A total of 3 key genes—myxovirus resistance-2 (MX2), oligoadenylate synthetase 1 (OAS1), and oligoadenylate synthetase 2 (OAS2)—were identified in combination with cell line samples, and the expressions of the 3 genes were verified separately. The results showed that MX2, OAS1, and OAS2 were highly expressed in LPS-treated cell lines compared to normal cell lines. The results of pathway enrichment analysis of the genes indicated that all 3 genes were enriched in the cytosolic DNA signalling and cytokine and cytokine receptor interaction signalling pathways; the results of functional enrichment analysis showed that all 3 were enriched in interferon-α response and interferon-γ response functions. Conclusions. This is important for the study of the pathogenesis and objective treatment of dermatomyositis and provides important reference information for the targeted therapy of dermatomyositis.

E74-Like Factor 3 Promotes Endometrial Cancer Cell Proliferation, Migration and Invasion via Regulating Mucin 1/Hypoxia-Inducible Factor 1α Pathway

2022 ◽  
Vol 12 (5) ◽  
pp. 926-932
Author(s):  
Xin Guan ◽  
Ning Sun
Keyword(s):  
Cell Proliferation ◽  
Endometrial Cancer ◽  
Western Blot ◽  
Cell Lines ◽  
Hypoxia Inducible Factor ◽  
Migration And Invasion ◽  
Mucin 1 ◽  
Positive Correlation ◽  
Ec Cells ◽  
High Level

High expression of E74-like factor 3 (ELF3) has been reported in type 1 endometrial cancer (EC). Bioinformatics analysis predicted a positive correlation with ELF3 and mucin 1 (MUC1)/hypoxiainducible factor 1α (HIF-1α), a previously identified cancer-promoting pathway. This study focused on the MUC1/HIF-1α-involved action mechanism of ELF3 in EC. ELF3 expression in EC cell lines was measured by RT-qPCR and western blot analysis. Following the expression of ELF3 was silent, cell proliferation was examined using CCK-8 and colony formation assay, cell migration and invasion were observed using wound healing and transwell assays. The effect of ELF1 silencing on MUC1/HIF-1α expression was detected by western blot. Rescue experiments incorporating pcDNA3.1(+)/MUC1 explored the interaction between ELF3 and MUC1/HIF-1α in EC cell proliferation, migration and invasion. ELF3 was found to be expressed at a high level in EC cell lines, and the silencing of it effectively inhibited EC cell proliferation. Moreover, ELF silencing also inhibited the migration and invasion of EC cells. Consistent with the database prediction, a positive correlation between ELF3 and MUC1/HIF-1α was observed. More importantly, MUC1 overexpression abated the promotive effect of ELF3 silencing on EC cell proliferation, migration and invasion. ELF3 promotes EC cell proliferation, migration and invasion by regulating MUC1/HIF-1α pathway. Thus, ELF3 as well as MUC1/HIF-1α pathway may be particle targets in the treatment of EC.

scholarly journals Systematic Functional Annotation and Visualization of Biological Networks

2015 ◽  
Author(s):  
Anastasia Baryshnikova
Keyword(s):  
Biological Networks ◽  
Large Scale ◽  
Functional Organization ◽  
Genetic Interaction ◽  
Interaction Network ◽  
Functional Enrichment ◽  
Functional Structure ◽  
Cancer Drug ◽  
Functional Connections ◽  
High Level

ABSTRACTLarge-scale biological networks map functional connections between most genes in the genome and can potentially uncover high level organizing principles governing cellular functions. These networks, however, are famously complex and often regarded as disordered masses of tangled interactions (“hairballs”) that are nearly impenetrable to biologists. As a result, our current understanding of network functional organization is very limited. To address this problem, I developed a systematic quantitative approach for annotating biological networks and examining their functional structure. This method, named Spatial Analysis of Functional Enrichment (SAFE), detects network regions that are statistically overrepresented for a functional group or a quantitative phenotype of interest, and provides an intuitive visual representation of their relative positioning within the network. By successfully annotating theSaccharomyces cerevisiaegenetic interaction network with Gene Ontology terms, SAFE proved to be sensitive to functional signals and robust to noise. In addition, SAFE annotated the network with chemical genomic data and uncovered a new potential mechanism of resistance to the anti-cancer drug bortezomib. Finally, SAFE showed that protein-protein interactions, despite their apparent complexity, also have a high level functional structure. These results demonstrate that SAFE is a powerful new tool for examining biological networks and advancing our understanding of the functional organization of the cell.

scholarly journals Identification of Aloperine as an anti-apoptotic Bcl2 protein inhibitor in glioma cells

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7652 ◽  
Author(s):  
Zhijie Xu ◽  
Xiang Wang ◽  
Xi Chen ◽  
Shuangshuang Zeng ◽  
Long Qian ◽  
...  
Keyword(s):  
Cell Lines ◽  
Glioma Cells ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Functional Enrichment ◽  
Analysis Tool ◽  
Limited Information ◽  
Human Glioma ◽  
Bcl2 Protein

Objective Aloperine (ALO), an alkaloid isolated from the leaves of Sophora alopecuroides, has been suggested to exhibit anti-inflammatory and anti-tumor properties and is traditionally used to treat various human diseases, including cancer. However, limited information is available about the mechanisms that determine the anti-tumor activities of ALO. Methods Herein, through comprehensive bioinformatics methods and in vitro functional analyses, we evaluated the detailed anti-tumor mechanisms of ALO. Results Using the databases Bioinformatics analysis tool for molecular mechanism of traditional Chinese medicine and PubChem Project, we identified the potential targets of ALO. A protein–protein interaction network was constructed to determine the relationship among these probable targets. Functional enrichment analysis revealed that ALO is potentially involved in the induction of apoptosis. In addition, molecular docking demonstrated that ALO expectedly docks into the active pocket of the Bcl2 protein, suggesting Bcl2 as a direct target of ALO. Moreover, western blot and qPCR analysis showed that ALO downregulated Bcl2 expression in human glioma cell lines, SK-N-AS and U118. Using flow cytometry methods, we further confirmed that ALO significantly promotes apoptosis in SK-N-AS and U118 cell lines, similar to the effect induced by ABT-737, a well-known Bcl2 inhibitor. In addition, Bcl-2 overexpression could rescue ALO-induced Bcl-2 inhibition and suppress pro-apoptotic effects in glioma cells. Conclusion Taken together, these findings suggest that the natural agent ALO effectively enhances apoptosis by acting as a potential Bcl2 inhibitor in human glioma cells.

scholarly journals Over-Expression and Prognostic Significance of FN1, Correlating with Immune Infiltrates in Thyroid Cancer

2021 ◽  
Author(s):  
Qi-Shun Geng ◽  
Zhi-Bo Shen ◽  
Li-Feng Li ◽  
Jie Zhao
Keyword(s):  
Gene Expression ◽  
Thyroid Cancer ◽  
Prognostic Significance ◽  
Interaction Network ◽  
Progression Free Survival ◽  
The Cancer Genome Atlas ◽  
Functional Enrichment ◽  
Clinical Prognosis ◽  
Network Analyses

Abstract Background. Thyroid cancer (THCA) is a malignancy affecting the endocrine system, which currently has no effective treatment due to a limited number of suitable drugs and prognostic markers. Methods. Three Gene Expression Omnibus (GEO) datasets were selected to identify differentially expressed genes (DEGs) between THCA and normal thyroid samples using GEO2R tools of National Center for Biotechnology Information. We identified hub gene FN1 using functional enrichment and protein–protein interaction network analyses. Subsequently, we evaluated the importance of gene expression on clinical prognosis using The Cancer Genome Atlas (TCGA) database and GEO datasets. MEXPRESS was used to investigate the correlation between gene expression and DNA methylation; the correlations between FN1 and cancer immune infiltrates were investigated using CIBERSORT. In addition, we assessed the effect of silencing FN1 expression, using an in vitro cellular model of THCA. Immunohistochemical(IHC) was used to elevate the correlation between CD276 and FN1. Results. FN1 expression was highly correlated with progression-free survival and moderately to strongly correlated with the infiltration levels of M2 macrophages and resting memory CD4 + T cells, as well as with CD276 expression. We suggest promoter hypermethylation as the mechanism underlying the observed changes in FN1 expression, as 20 CpG sites in 507 THCA cases in TCGA database showed a negative correlation with FN1 expression. In addition, silencing FN1 expression suppressed clonogenicity, motility, invasiveness, and expression of CD276 in vitro. The correlation between FN1 and CD276 was further confirmed by immunohistochemical. Conclusion. Our findings show that FN1 expression levels correlate with prognosis and immune infiltration levels in THCA, suggesting that FN1 expression be used as immunity-related biomarker and therapeutic target in THCA.

scholarly journals Histone 2A Family Member J Drives Mesenchymal Transition and Temozolomide Resistance in Glioblastoma Multiforme

Cancers ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 98 ◽  
Author(s):  
Hsun-Hua Lee ◽  
Che-Hsuan Lin ◽  
Hui-Yu Lin ◽  
Chia-Hao Kuei ◽  
Jing-Quan Zheng ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Family Member ◽  
Cell Lines ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Mesenchymal Transition ◽  
Tnf Α ◽  
High Level

Glioblastoma multiforme (GBM) is the most aggressive brain tumor and has a poor prognosis and is poorly sensitive to radiotherapy or temozolomide (TMZ) chemotherapy. Therefore, identifying new biomarkers to predict therapeutic responses of GBM is urgently needed. By using The Cancer Genome Atlas (TCGA) database, we found that the upregulation of histone 2A family member J (H2AFJ), but not other H2AFs, is extensively detected in the therapeutic-insensitive mesenchymal, IDH wildtype, MGMT unmethylated, or non-G-CIMP GBM and is associated with poor TMZ responsiveness independent of radiation. Similar views were also found in GBM cell lines. Whereas H2AFJ knockdown diminished TMZ resistance, H2AFJ overexpression promoted TMZ resistance in a panel of GBM cell lines. Gene set enrichment analysis (GSEA) revealed that H2AFJ upregulation accompanied by the activation of TNF-α/NF-κB and IL-6/STAT3-related pathways is highly predicted. Luciferase-based promoter activity assay further validated that the activities of NF-κB and STAT3 are causally affected by H2AFJ expression in GBM cells. Moreover, we found that therapeutic targeting HADC3 by tacedinaline or NF-κB by ML029 is likely able to overcome the TMZ resistance in GBM cells with H2AFJ upregulation. Significantly, the GBM cohorts harboring a high-level H2AFJ transcript combined with high-level expression of TNF-α/NF-κB geneset, IL-6/STAT3 geneset or HADC3 were associated with a shorter time to tumor repopulation after initial treatment with TMZ. These findings not only provide H2AFJ as a biomarker to predict TMZ therapeutic effectiveness but also suggest a new strategy to combat TMZ-insensitive GBM by targeting the interaction network constructed by TNF-α/NF-κB, IL-6/STAT3, HDAC3, and H2AFJ.

Braf Mutations Are Associated With High Levels of Phosphorylated RKIP in Melanoma Cell Lines: Potential Prognostic Significance

2011 ◽  
Vol 2 (2) ◽  
pp. 189-194 ◽  
Author(s):  
Sara Huerta-Yepez ◽  
S. Ekmekcioglu ◽  
C. M. Rivera-Pazos ◽  
G. Antonio-Andres ◽  
Mario I. Vega ◽  
...  
Keyword(s):  
Cell Lines ◽  
Melanoma Cell ◽  
Prognostic Significance ◽  
Braf Mutations ◽  
Melanoma Cell Lines

scholarly journals Identification of potential biomarkers for abdominal pain in IBS patients by bioinformatics approach

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Zhongyuan Lin ◽  
Yimin Wang ◽  
Shiqing Lin ◽  
Decheng Liu ◽  
Guohui Mo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Irritable Bowel Syndrome ◽  
Abdominal Pain ◽  
Gastrointestinal Disease ◽  
Rectal Mucosa ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Functional Enrichment ◽  
Irritable Bowel ◽  
Potential Biomarkers

Abstract Background Irritable bowel syndrome (IBS) is the most common functional gastrointestinal disease characterized by chronic abdominal discomfort and pain. The mechanisms of abdominal pain, as a relevant symptom, in IBS are still unclear. We aimed to explore the key genes and neurobiological changes specially involved in abdominal pain in IBS. Methods Gene expression data (GSE36701) was downloaded from Gene Expression Omnibus database. Fifty-three rectal mucosa samples from 27 irritable bowel syndrome with diarrhea (IBS-D) patients and 40 samples from 21 healthy volunteers as controls were included. Differentially expressed genes (DEGs) between two groups were identified using the GEO2R online tool. Functional enrichment analysis of DEGs was performed on the DAVID database. Then a protein–protein interaction network was constructed and visualized using STRING database and Cytoscape. Results The microarray analysis demonstrated a subset of genes (CCKBR, CCL13, ACPP, BDKRB2, GRPR, SLC1A2, NPFF, P2RX4, TRPA1, CCKBR, TLX2, MRGPRX3, PAX2, CXCR1) specially involved in pain transmission. Among these genes, we identified GRPR, NPFF and TRPA1 genes as potential biomarkers for irritating abdominal pain of IBS patients. Conclusions Overexpression of certain pain-related genes (GRPR, NPFF and TRPA1) may contribute to chronic visceral hypersensitivity, therefore be partly responsible for recurrent abdominal pain or discomfort in IBS patients. Several synapses modification and biological process of psychological distress may be risk factors of IBS.

scholarly journals Stromal hyaluronan accumulation is associated with low immune response and poor prognosis in pancreatic cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kyösti Tahkola ◽  
Maarit Ahtiainen ◽  
Jukka-Pekka Mecklin ◽  
Ilmo Kellokumpu ◽  
Johanna Laukkarinen ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Cell ◽  
Geographical Area ◽  
Prognostic Significance ◽  
Staining Intensity ◽  
Ductal Adenocarcinoma ◽  
Poor Survival ◽  
Negative Prognostic Factor ◽  
High Level ◽  
Immune Cell Score

AbstractHyaluronan (HA) accumulation has been associated with poor survival in various cancers, but the mechanisms for this phenomenon are still unclear. The aim of this study was to investigate the prognostic significance of stromal HA accumulation and its association with host immune response in pancreatic ductal adenocarcinoma (PDAC). The study material consisted of 101 radically treated patients for PDAC from a single geographical area. HA staining was evaluated using a HA-specific probe, and the patterns of CD3, CD8, CD73 and PD-L1 expression were evaluated using immunohistochemistry. HA staining intensity of tumour stromal areas was assessed digitally using QuPath. CD3- and CD8-based immune cell score (ICS) was determined. High-level stromal HA expression was significantly associated with poor disease-specific survival (p = 0.037) and overall survival (p = 0.013) In multivariate analysis, high-level stromal HA expression was an independent negative prognostic factor together with histopathological grade, TNM stage, CD73 positivity in tumour cells and low ICS. Moreover, high-level stromal HA expression was associated with low ICS (p = 0.017). In conclusion, stromal HA accumulation is associated with poor survival and low immune response in PDAC.

scholarly journals Investigation and Functional Enrichment Analysis of the Human Host Interaction Network with Common Gram-Negative Respiratory Pathogens Predicts Possible Association with Lung Adenocarcinoma

2021 ◽  
Vol 28 (1) ◽  
pp. 20-33
Author(s):  
Lydia-Eirini Giannakou ◽  
Athanasios-Stefanos Giannopoulos ◽  
Chrissi Hatzoglou ◽  
Konstantinos I. Gourgoulianis ◽  
Erasmia Rouka ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Cell Junctions ◽  
Respiratory Pathogens ◽  
Gram Negative ◽  
Human Proteins ◽  
Apoptotic Pathways

Haemophilus influenzae (Hi), Moraxella catarrhalis (MorCa) and Pseudomonas aeruginosa (Psa) are three of the most common gram-negative bacteria responsible for human respiratory diseases. In this study, we aimed to identify, using the functional enrichment analysis (FEA), the human gene interaction network with the aforementioned bacteria in order to elucidate the full spectrum of induced pathogenicity. The Human Pathogen Interaction Database (HPIDB 3.0) was used to identify the human proteins that interact with the three pathogens. FEA was performed via the ToppFun tool of the ToppGene Suite and the GeneCodis database so as to identify enriched gene ontologies (GO) of biological processes (BP), cellular components (CC) and diseases. In total, 11 human proteins were found to interact with the bacterial pathogens. FEA of BP GOs revealed associations with mitochondrial membrane permeability relative to apoptotic pathways. FEA of CC GOs revealed associations with focal adhesion, cell junctions and exosomes. The most significantly enriched annotations in diseases and pathways were lung adenocarcinoma and cell cycle, respectively. Our results suggest that the Hi, MorCa and Psa pathogens could be related to the pathogenesis and/or progression of lung adenocarcinoma via the targeting of the epithelial cellular junctions and the subsequent deregulation of the cell adhesion and apoptotic pathways. These hypotheses should be experimentally validated.

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