scholarly journals Blocking of EGFR Signaling Is a Latent Strategy for the Improvement of Prognosis of HPV-Induced Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Jianfa Qiu ◽  
Feifei Hu ◽  
Tingting Shao ◽  
Yuqiang Guo ◽  
Zongmao Dai ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Molecular Mechanisms ◽  
Interaction Network ◽  
Critical Factor ◽  
Enrichment Analysis ◽  
Head And Neck Carcinoma ◽  
Hpv Infection ◽  
Human Interaction ◽  
Hpv E7 ◽  
Significant Difference

Human papillomavirus (HPV) is a double-stranded DNA (dsDNA) virus, and its high-risk subtypes increase cancer risks. However, the mechanism of HPV infection and pathogenesis still remain unclear. Therefore, understanding the molecular mechanisms and the pathogenesis of HPV are crucial in the prevention of HPV-related cancers. In this study, we analyzed cervix squamous cell carcinoma (CESC) and head and neck carcinoma (HNSC) combined data to investigate various HPV-induced cancer common features. We showed that epidermal growth factor receptor (EGFR) was downregulated in HPV-positive (HPV+) cancer, and that HPV+ cancer patients exhibited better prognosis than HPV-negative (HPV−) cancer patients. Our study also showed that TP53 mutation rate is lower in HPV+ cancer than in HPV− cancer and that TP53 can be modulated by HPV E7 protein. However, there was no significant difference in the expression of wildtype TP53 in both groups. Subsequently, we constructed HPV-human interaction network and found that EGFR is a critical factor. From the network, we also noticed that EGFR is regulated by HPV E7 protein and hsa-miR-944. Moreover, while phosphorylated EGFR is associated with a worse prognosis, EGFR total express level is not significantly correlated with prognosis. This indicates that EGFR activation will induce a worse outcome in HPV+ cancer patients. Further enrichment analysis showed that EGFR downstream pathway and cancer relative pathway are diversely activated in HPV+ cancer and HPV− cancer. In summary, HPV E7 protein downregulates EGFR that downregulates phosphorylated EGFR and inhibit EGFR-related pathways which in turn and consequently induce better prognosis.

scholarly journals Blocking of EGFR Signaling is a Latent Strategy for the Improvement of Prognosis of HPV Induced Cancer

2020 ◽  
Author(s):  
Jianfa Qiu ◽  
Feifei Hu ◽  
Tingting Shao ◽  
Yuqiang Guo ◽  
Zongmao Dai ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Structure Prediction ◽  
Molecular Mechanisms ◽  
Interaction Network ◽  
Hpv Infection ◽  
Human Interaction ◽  
Hpv E7 ◽  
Significant Difference ◽  
Cancer Types ◽  
The Common

AbstractHuman papillomavirus (HPV) is a dsDNA virus and its high-risk subtypes increase cancer risks. Yet, the mechanism of HPV infection and pathogenesis still remain unclear. Therefore, understanding the molecular mechanisms, and the pathogenesis of HPV are crucial in the prevention of HPV related cancers. In this study, we analyzed cervix squamous cell carcinoma (CESC) and head and neck carcinoma (HNSC) combined data to investigate various HPV induced cancer common feature. We showed that epidermal growth factor receptor (EGFR) was downregulated in HPV positive (HPV+) cancer, and that HPV+ cancer patients exhibited better prognosis than HPV negative (HPV−) cancer patients. Our study also showed that TP53 mutation rate is lower in HPV+ cancer than in HPV− cancer and that TP53 can be modulated by HPV E7 protein. However, there was no significant difference in the expression of wildtype TP53 in both groups. Subsequently, we constructed HPV-human interaction network and found that EGFR is a critical factor. From the network, we also noticed that EGFR is regulated by HPV E7 protein and hsa-miR-944. Moreover, while phosphorylated EGFR is associated with a worse prognosis, EGFR total express level is not significantly correlated with prognosis. This indicates that EGFR activation will induce a worse outcome in HPV+ cancer patients. Further enrichment analysis showed that EGFR downstream pathway and cancer relative pathway are diversely activated in HPV+ cancer and HPV− cancer. In summary, HPV E7 protein downregulates EGFR that downregulates phosphorylated EGFR and inhibit EGFR related pathways which in turn and consequently induce better prognosis.ImportanceAlthough HPV infection has been studied in various cancer types, there are only limited studies that have focused on the common effect of HPV related cancer. Consequently, this study focused on CESC and HNSC, two cancer types with high HPV infection proportion in cohort, thereby, intending to dig out the common effects and mechanisms of HPV+ cancers.Unlike some virus-human interaction prediction studies, the P-HIPSter database provides virus-human protein interaction based on protein structure prediction. Through this data, our interaction network was able to uncover previously unnoticed protein interactions. Our finding revealed that HPV infection caused various gene expression differences, and a great amount of which interact with EGFR, a cancer related gene. Therefore, since EGFR is associated with HPV+ cancer patients’ survival, some FDA proved EGFR inhibitors would be potential anti-HPV drugs.

Analysis of Expression Profiles of mRNA and lncRNA in Oviduct During Estrus Phase of Sheep (Ovis Aries) with Two Fecundity (FecB Gene) Genotypes

2021 ◽  
Author(s):  
Weihao Chen ◽  
Zhifeng Li ◽  
Wei Sun ◽  
Mingxing Chu
Keyword(s):  
Embryo Development ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Ovis Aries ◽  
Functional Enrichment ◽  
Saga Complex ◽  
Rna Seq ◽  
Estrus Phase

Abstract Background:In sheep, FecB is the essential biomarker of the fertility, previous researches have provided a detailed insight on the regulation involved estrus phase and FecB in the reproductive-related tissues including hypothalamus, pituitary, and ovary. However, as the host of embryo development and connection between the ovary and the uterus, little is known about the interaction between mRNAs and lncRNAs in sheep oviduct. In the present study, RNA-Seq was performed to identify the transcriptomic profiles of mRNAs and lncRNAs in oviduct during estrus phase of sheep with FecBBB/++ genotypes.Results:In total, 21,863 lncRNAs and 43,674 mRNAs were identified, 57 DE lncRNAs and 637 DE mRNAs were revealed in the comparisons between follicular phase and luteal phase, 26 DE lncRNAs and 421 DE lncRNAs were revealed in the comparisons between FecB BB genotype and FecB ++ genotype. Functional enrichment analysis suggested that GO and KEGG terms related to reproduction such as SAGA complex, ATP-binding cassette (ABC), Nestin, and Hippo signalling pathway. DE-interaction network suggested that LNC_018420 maybe the key regulators related to embryo development in sheep oviduct.Conclusion:This was the first study to reveal the transcriptomic profiles of mRNAs and lncRNAs in the oviduct of FecB BB/++ sheep at estrus phase using RNA-Seq. Our findings can provide new understanding on the molecular mechanisms of mRNAs and lncRNAs underlying sheep embryo development and also opening new lines of investigation in sheep reproduction.

scholarly journals Gene Prioritization through Consensus Strategy, Enrichment Methodologies Analysis, and Networking for Osteosarcoma Pathogenesis

2020 ◽  
Vol 21 (3) ◽  
pp. 1053 ◽  
Author(s):  
Alejandro Cabrera-Andrade ◽  
Andrés López-Cortés ◽  
Gabriela Jaramillo-Koupermann ◽  
César Paz-y-Miño ◽  
Yunierkis Pérez-Castillo ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Bone Cancer ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Protein Protein Interaction ◽  
Pathogenic Genes ◽  
Total List ◽  
Consensus Strategy ◽  
Primary Bone ◽  
Molecular Etiology

Osteosarcoma is the most common subtype of primary bone cancer, affecting mostly adolescents. In recent years, several studies have focused on elucidating the molecular mechanisms of this sarcoma; however, its molecular etiology has still not been determined with precision. Therefore, we applied a consensus strategy with the use of several bioinformatics tools to prioritize genes involved in its pathogenesis. Subsequently, we assessed the physical interactions of the previously selected genes and applied a communality analysis to this protein–protein interaction network. The consensus strategy prioritized a total list of 553 genes. Our enrichment analysis validates several studies that describe the signaling pathways PI3K/AKT and MAPK/ERK as pathogenic. The gene ontology described TP53 as a principal signal transducer that chiefly mediates processes associated with cell cycle and DNA damage response It is interesting to note that the communality analysis clusters several members involved in metastasis events, such as MMP2 and MMP9, and genes associated with DNA repair complexes, like ATM, ATR, CHEK1, and RAD51. In this study, we have identified well-known pathogenic genes for osteosarcoma and prioritized genes that need to be further explored.

scholarly journals A Network Pharmacology Approach to Uncover the Mechanisms of Shen-Qi-Di-Huang Decoction against Diabetic Nephropathy

2018 ◽  
Vol 2018 ◽  
pp. 1-14 ◽  
Author(s):  
Sha Di ◽  
Lin Han ◽  
Qing Wang ◽  
Xinkui Liu ◽  
Yingying Yang ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Network Pharmacology ◽  
Pathway Enrichment Analysis ◽  
Protein Protein Interaction ◽  
Regulation Of Blood Pressure ◽  
Protein Protein Interaction Network

Shen-Qi-Di-Huang decoction (SQDHD), a well-known herbal formula from China, has been widely used in the treatment of diabetic nephropathy (DN). However, the pharmacological mechanisms of SQDHD have not been entirely elucidated. At first, we conducted a comprehensive literature search to identify the active constituents of SQDHD, determined their corresponding targets, and obtained known DN targets from several databases. A protein-protein interaction network was then built to explore the complex relations between SQDHD targets and those known to treat DN. Following the topological feature screening of each node in the network, 400 major targets of SQDHD were obtained. The pathway enrichment analysis results acquired from DAVID showed that the significant bioprocesses and pathways include oxidative stress, response to glucose, regulation of blood pressure, regulation of cell proliferation, cytokine-mediated signaling pathway, and the apoptotic signaling pathway. More interestingly, five key targets of SQDHD, named AKT1, AR, CTNNB1, EGFR, and ESR1, were significant in the regulation of the above bioprocesses and pathways. This study partially verified and predicted the pharmacological and molecular mechanisms of SQDHD on DN from a holistic perspective. This has laid the foundation for further experimental research and has expanded the rational application of SQDHD in clinical practice.

scholarly journals Identification of Potential Key Genes and Molecular Mechanisms of Medulloblastoma Based on Integrated Bioinformatics Approach

2022 ◽  
Vol 2022 ◽  
pp. 1-17
Author(s):  
Md. Rakibul Islam ◽  
Lway Faisal Abdulrazak ◽  
Mohammad Khursheed Alam ◽  
Bikash Kumar Paul ◽  
Kawsar Ahmed ◽  
...  
Keyword(s):  
Gene Expression ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Clinical Information ◽  
Gene Expression Omnibus ◽  
Hub Genes ◽  
New Treatments

Background. Medulloblastoma (MB) is the most occurring brain cancer that mostly happens in childhood age. This cancer starts in the cerebellum part of the brain. This study is designed to screen novel and significant biomarkers, which may perform as potential prognostic biomarkers and therapeutic targets in MB. Methods. A total of 103 MB-related samples from three gene expression profiles of GSE22139, GSE37418, and GSE86574 were downloaded from the Gene Expression Omnibus (GEO). Applying the limma package, all three datasets were analyzed, and 1065 mutual DEGs were identified including 408 overexpressed and 657 underexpressed with the minimum cut-off criteria of ∣ log   fold   change ∣ > 1 and P < 0.05 . The Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and WikiPathways enrichment analyses were executed to discover the internal functions of the mutual DEGs. The outcomes of enrichment analysis showed that the common DEGs were significantly connected with MB progression and development. The Search Tool for Retrieval of Interacting Genes (STRING) database was used to construct the interaction network, and the network was displayed using the Cytoscape tool and applying connectivity and stress value methods of cytoHubba plugin 35 hub genes were identified from the whole network. Results. Four key clusters were identified using the PEWCC 1.0 method. Additionally, the survival analysis of hub genes was brought out based on clinical information of 612 MB patients. This bioinformatics analysis may help to define the pathogenesis and originate new treatments for MB.

scholarly journals The Study of Angptl4-Modulated Podocyte Injury in IgA Nephropathy

2021 ◽  
Vol 11 ◽  
Author(s):  
Sha Jia ◽  
Xiaofeng Peng ◽  
Ludan Liang ◽  
Ying Zhang ◽  
Meng Li ◽  
...  
Keyword(s):  
Iga Nephropathy ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Healthy Controls ◽  
Podocyte Injury ◽  
Protein Protein Interaction ◽  
Promising Tool ◽  
Significant Difference ◽  
Limma Package

BackgroundIncreasing evidence shows that Angptl4 affects proteinuria in podocytes injured kidney disease, however, whether there is a relationship between Angptl4 and IgA nephropathy (IgAN) has not been studied yet.MethodsPlasma and urine samples were obtained from 71 patients with IgAN and 61 healthy controls. Glomeruli from six renal biopsy specimens (three IgAN patients and three healthy controls) were separated by RNA-Seq. Differentially expressed genes (DEGs) related to podocytes and Angptl4 between IgAN patients and healthy controls were performed using the Limma package. Gene set enrichment analysis was used to determine whether there was a statistically significant difference between the two groups. STRING was used to create a protein-protein interaction network of DEGs. Association analysis between Angptl4 levels and clinical features of IgAN was performed.ResultsThirty-three podocyte-related and twenty-three Angpt4-related DEGs were found between IgAN patients and healthy controls. By overlapping the genes, FOS and G6PC were found to be upregulated in IgAN patients, while MMP9 was downregulated in IgAN patients. Plasma and urine Angptl4 levels were closely related to the degree of podocyte injury and urine protein, but not to the protein-creatine ratio.ConclusionOur findings show that Angptl4 levels in plasma and urine are related to podocyte damage and, therefore, may be a promising tool for assessing the severity of IgAN patients to identify and reverse the progression to ESRD.

scholarly journals Deciphering of Key Pharmacological Pathways of Poria Cocos Intervention in Breast Cancer Based on Integrated Pharmacological Method

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Xiaoran Ma ◽  
Jibiao Wu ◽  
Cun Liu ◽  
Jie Li ◽  
Shixia Dong ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Molecular Mechanisms ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Network Pharmacology ◽  
Breast Cancers ◽  
Active Ingredients ◽  
Poria Cocos ◽  
Pharmacological Method

Objective. Poria cocos (Fuling), a natural plant, has recently emerged as a promising strategy for cancer treatment. However, the molecular mechanisms of Poria cocos action in breast cancer remain poorly understood. Methods. TCMSP database was used to screen the potential active ingredients in Poria cocos. GEO database was used to identify differentially expressed genes. Network pharmacology was used to identify the specific pathways and key target proteins related to breast cancer. Finally, molecular docking was used to validate the results. Results. In our study, 237 targets were predicted for 15 potential active ingredients found in Poria cocos. An interaction network of predicted targets and genes differentially regulated in breast cancers was constructed. Based on the constructed network and further analysis including network topology, KEGG, survival analysis, and gene set enrichment analysis, 3 primary nodes were identified as key potential targets that were significantly enriched in the PPAR signaling pathway. Conclusion. The results showed that potential active ingredients of Poria cocos might interfere with breast cancer through synergistic regulation of PTGS2, ESR1, and FOS.

scholarly journals Use of bioinformatic analyses in identifying characteristic genes and mechanisms active in the progression of idiopathic thrombocytopenic purpura in individuals with different phenotypes

2020 ◽  
Vol 48 (11) ◽  
pp. 030006052097143
Author(s):  
Mengyi Zhang ◽  
Binhan Guo
Keyword(s):  
Gene Expression ◽  
Idiopathic Thrombocytopenic Purpura ◽  
Molecular Mechanisms ◽  
Treatment Strategies ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Gene Expression Omnibus ◽  
Newly Diagnosed ◽  
Thrombocytopenic Purpura ◽  
Protein Protein Interaction

Objective To explore the mechanism underlying the progression of newly diagnosed idiopathic thrombocytopenic purpura (ITP) to its chronic or remission state using bioinformatic methods. Methods GSE56232 and GSE46922 gene expression profile datasets were downloaded from Gene Expression Omnibus (GEO). Differentially expressed genes were identified and characteristic genes were screened by weighted gene co-expression network analysis. These genes were used for function enrichment analysis and construction of a protein–protein interaction network. Finally, characteristic genes were verified to determine potential molecular mechanisms underlying ITP progression. Results We found that characteristic genes in the chronic ITP group were mainly involved in intracellular processes and ion binding, while characteristic genes in the remission ITP group were involved in intracellular processes and nuclear physiological activities. We identified a sub-network of characteristic genes, LMNA, JUN, PRKACG, SMC3, which may indicate the mechanism by which newly diagnosed ITP progresses to chronic. Although no meaningful signaling pathways were found, the expression of NR3C1, TPR, SMC4, PANBP2, CHD1, and U2SURP may affect ITP progression from newly diagnosed to remission. Conclusion Our findings improve the understanding of the pathogenesis and progression of ITP, and may provide new directions for the development of treatment strategies.

scholarly journals Identification and Interaction Analysis of Significant Genes and MicroRNAs in Pterygium

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Siying He ◽  
Hui Sun ◽  
Yifang Huang ◽  
Shiqi Dong ◽  
Chen Qiao ◽  
...  
Keyword(s):  
Differentially Expressed Genes ◽  
Molecular Mechanisms ◽  
Interaction Analysis ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Gene Expression Omnibus ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Differentially Expressed Mirnas

Purpose. MiRNAs have been widely analyzed in the occurrence and development of many diseases, including pterygium. This study aimed to identify the key genes and miRNAs in pterygium and to explore the underlying molecular mechanisms. Methods. MiRNA expression was initially extracted and pooled by published literature. Microarray data about differentially expressed genes was downloaded from Gene Expression Omnibus (GEO) database and analyzed with the R programming language. Functional and pathway enrichment analyses were performed using the database for Annotation, Visualization and Integrated Discovery (DAVID). The protein-protein interaction network was constructed with the STRING database. The associations between chemicals, differentially expressed miRNAs, and differentially expressed genes were predicted using the online resource. All the networks were constructed using Cytoscape. Results. We found that 35 miRNAs and 301 genes were significantly differentially expressed. Functional enrichment analysis showed that upregulated genes were significantly enriched in extracellular matrix (ECM) organization, while downregulated genes were mainly involved in cell death and apoptotic process. Finally, we concluded the chemical-gene affected network, miRNA-mRNA interacted networks, and significant pathway network. Conclusion. We identified lists of differentially expressed miRNAs and genes and their possible interaction in pterygium. The networks indicated that ECM breakdown and EMT might be two major pathophysiological mechanisms and showed the potential significance of PI3K-Akt signalling pathway. MiR-29b-3p and collagen family (COL4A1 and COL3A1) might be new treatment target in pterygium.

scholarly journals Finding the “switch” in platelet activation Prediction of key mediators involved in platelet hyperreactivity using a novel network biology approach

2021 ◽  
Author(s):  
TP Lemmens ◽  
DM Coenen ◽  
ICL Niessen ◽  
F Swieringa ◽  
SLM Coort ◽  
...  
Keyword(s):  
Platelet Activation ◽  
Molecular Mechanisms ◽  
Shape Change ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Adenosine Monophosphate ◽  
Adenosine Diphosphate ◽  
Network Biology ◽  
Small Gtpases ◽  
Platelet Activity

Abstract The healthy endothelium controls platelet activity through release of prostaglandin I2 (PGI2) and nitric oxide. The loss of this natural brake on platelet activity can cause platelets to become hyperreactive. PGI2 attenuates platelet activation by adenosine diphosphate (ADP) through stimulation of cyclic adenosine monophosphate (cAMP) production and subsequent phosphorylation changes by protein kinase A (PKA). We hypothesize that proteins/processes involved in platelet hyperactivity downstream of the cAMP-PKA pathway can serve as a “switch” in platelet activation and inhibition. We designed a network biology approach to explore the entangled platelet signaling pathways downstream of PGI2 and ADP. The STRING database was used to build a protein-protein interaction network from proteins of interest in which we integrate a quantitative platelet proteome dataset with pathway information, relative RNA expression of hematopoietic cells, the likelihood of the proteins being phosphorylated by PKA, and drug-target information from DrugBank in a biological network. We distilled 30 proteins from existing phosphoproteomics datasets (PXD000242 and PXD001189) that putatively can be “turned on” after ADP-mediated platelet activation and subsequently switched “off” after platelet inhibition with iloprost. Enrichment analysis revealed biological processes related to vesicle secretion and cytoskeletal reorganization to be overrepresented coinciding with topological clusters in the network. Our method highlights novel proteins related to vesicle transport, platelet shape change, and small GTPases as potential switch proteins in platelet activation and inhibition. Our novel approach demonstrates the benefit of data integration by combining tools and datasets and visualization to obtain a more complete picture of complex molecular mechanisms.

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