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Eight hub genes as potential biomarkers for breast cancer diagnosis and prognosis:A TCGA-based study

World Journal of Clinical Oncology 2022年第8期13卷 675-687页

作者： Nan Liu Guo-Duo Zhang Ping Bai Li Su Hao Tian Miao He Department of Hematology and Oncology Chongqing Traditional Chinese Medicine HospitalChengdu University of Traditional Chinese MedicineChongqing 400011China Department of Breast and Thyroid Surgery Southwest HospitalArmy Medical UniversityChongqing 400038China

BACKGROUND Breast cancer(BC)is the most common malignant tumor in *** To investigate BC-associated hub genes to obtain a better understanding of BC *** In total,1203 BC samples were downloaded from The Cancer Genome Atlas database,which included 113 normal samples and 1090 tumor *** limma package of R software was used to analyze the differentially expressed genes(DEGs)in tumor tissues compared with normal *** cluster Profiler package was used to perform Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis of upregulated and downregulated *** Cox regression was conducted to explore the DEGs with statistical ***-protein interaction(PPI)network analysis was employed to investigate the hub genes using the CytoHubba plug-in of Cytoscape *** analyses of the hub genes were carried out using the Kaplan-Meier *** expression level of these hub genes was validated in the Gene Expression Profiling Interactive Analysis database and Human protein Atlas *** A total of 1317 DEGs(fold change>2;Pinteraction,cell cycle,and the p53 signaling pathway(Pinteraction,peroxisome proliferator-activated receptor signaling pathway,and AMP-activated protein kinase signaling pathway(P<0.01).CONCLUSION In view of the results of PPI analysis,which were verified by survival and expression analyses,we conclude that MAD2L1,PLK1,SAA1,CCNB1,SHCBP1,KIF4A,ANLN,and ERCC6L may act as biomarkers for the diagnosis and prognosis in BC patients.

关键词： Breast cancer Bioinformatics Hub gene The Cancer Genome Atlas protein-protein interaction

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Analysis of Proteotranscriptomics Landscape Reveals Differentially Regulated Pathways in Toxoplasma gondii Infected Mouse Liver

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Computational Molecular Bioscience 2022年第1期12卷 20-57页

作者： Tanzina Tarannum Md. Saruar Alam Atiqur Rahman Sajib Chakraborty Hossain Uddin Shekhar Taibur Rahman Laboratory of Infection Biology Department of Biochemistry and Molecular Biology University of Dhaka Dhaka Bangladesh Laboratory Clinical Biochemistry and Translational Medicine Department of Biochemistry and Molecular Biology University of Dhaka Dhaka Bangladesh

Toxoplasma gondii (T. gondii) an intracellular protozoan parasite, infects mammals including human population world-wide. Upon primary infection, the parasite contributes to mild flu like symptoms in immune competent host, but life threatening complication is seen in immune compromised patients and in pregnant women. Understanding the host-parasite interaction is critical for understanding the pathogenesis and biology parasite reactivation in the host. In this study, we used proteotrasncriptomics analyses by integrating the transcriptomics and proteomics data of T. gondii infected mouse liver to uncover the effector molecules responsible for disease pathogenesis that can be used as candidate markers for diagnosis and drug target. With this aim, we systematically integrated transcriptomicand proteomic data, representing the parasite infected mouse liver. Out of 2758 differentially expressed genes (DEGs) and 301 differentially expressed proteins (DEPs), 159 overlapping genes were identified. Among them, 86 genes were upregulated and 72 were downregulated in their respective mRNA and protein levels in the infected condition. Gene Ontology (GO) analysis revealed that the upregulated genes were mostly associated with immune system processes whereas the downregulated genes were involved in oxidation-reduction process and metabolism of lipid, and fatty acids. protein-protein interaction (PPI) network analysis uncovered an interaction-hub including, Psmb8, Psmb9 and Tap1 for upregulated proteins and Cyp1A2, Cyp4A10 and Cyp3A11 for down-regulated proteins. Further studies are needed to validating these effector molecules. These molecules are likely to play a vital role in disease pathogenesis, as well as can be used as potential diagnostic marker and drug target candidates.

关键词： Toxoplasma gondii Transcriptome Proteome Mouse Liver Differentially Expressed Genes and proteins Gene Ontology Analysis protein-protein interaction Hub-proteins Homology Modeling Effector Molecules

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Docking of Human Band 3 Anion Transporter proteins with Their Plasmodium falciparum Interactors Based on Short Linear Motifs

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American Journal of Molecular Biology 2024年第4期14卷 187-200页

作者： Fatoumata Gniné Fofana Ayoub Ksouri Cheickna Cisse Oussema Souiai Alia Benkahla Hedmon Okella Mamadou Sangare Jeffrey G. Shaffer Seydou Doumbia Mamadou Wele African Center of Excellence in Bioinformatics University of Sciences Techniques and Technologies of Bamako (USTTB) Bamako Mali Laboratory of BioInformatics BioMathematics and BioStatistics (BIMS) Institut Pasteur de Tunis University of Tunis El Manar Tunis Tunisia School of Veterinary Medicine University of California Davis Tulare USA Department of Biostatistics and Data Science Tulane University School of Public Health and Tropical Medicine New Orleans USA University Clinical Research Centre (UCRC) USTTB Bamako Mali

Plasmodium (P.) falciparum is a pathogen that causes severe forms of malaria. protein interactions have been shown to occur between P. falciparum and human erythrocytes in human blood. The Band 3 Anion Transporter (B3AT) protein is considered the main invasive pathway for the parasite in erythrocytes that causes clinical symptoms for malaria in humans. The interactions between P. falciparum parasites and erythrocytes along this receptor have previously been explored. Short linear motifs (SLIMs) are short linear mediator sequences that involve several biological processes, acting as mediators of protein interactions identifiable by computational tools such as SLiMFinder. For a given protein, the identification of SLIMs allows predicting its interactors. Using the SLIMs approach, protein-protein interaction network analyses between P. falciparum and its human host, were used to identify a tryptophan-rich protein, A5K5E5_PLAVS as an essential interactor of B3AT. To better understand the interaction mechanism, a guided protein-protein docking approach based on SLIM motifs was performed for human B3AT and A5K5E5_PLAVS. The highlights of this important interaction between P. falciparum and its human host have the potential to pave the way to identify new therapeutic candidates.

关键词： Malaria protein-protein Docking protein-protein interaction Short Linear Motifs

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protein arginine methyltransferase 6 is a novel substrate of protein arginine methyltransferase 1

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World Journal of Biological Chemistry 2023年第5期14卷 84-98页

作者： Meng-Tong Cao You Feng Y George Zheng Department of Pharmaceutical and Biomedical Sciences University of GeorgiaAthensGA 30602United States

BACKGROUND Post-translational modifications play key roles in various biological *** arginine methyltransferases(PRMTs)transfer the methyl group to specific arginine *** PRMT1 and PRMT6 have emerges as crucial factors in the development and progression of multiple cancer *** posit that PRMT1 and PRMT6 might interplay directly or in-directly in multiple ways accounting for shared disease *** To investigate the mechanism of the interaction between PRMT1 and *** Gel electrophoresis autoradiography was performed to test the methyltranferase activity of PRMTs and characterize the kinetics parameters of *** chromatography-tandem mass spectrometryanalysis was performed to detect the PRMT6 methylation *** In this study we investigated the interaction between PRMT1 and PRMT6,and PRMT6 was shown to be a novel substrate of *** identified specific arginine residues of PRMT6 that are methylated by PRMT1,with R106 being the major methylation *** biochemical and cellular data showed that PRMT1 downregulates the enzymatic activity of PRMT6 in histone H3 *** PRMT6 is methylated by PRMT1 and R106 is a major methylation site induced by ***1 methylation suppresses the activity of PRMT6.

关键词： Posttranslational modification Arginine methylation protein arginine methyltransferase 1 protein arginine methyltransferase 6 Cross-talk protein-protein interaction

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Transcriptomic Analysis of Metastatic Colorectal Tumor with Low Mutational Burden

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Proceedings of Anticancer Research 2024年第1期8卷 43-53页

作者： Ke Wang Shuo Mu School of Pharmacy Jiangsu UniversityZhenjiang 212013Jiangsu ProvinceChina OrigiMed Shanghai 201100China

Objective:To identify potential drug targets for metastasis colorectal cancer(CRC)patients with low mutational burden by examining differences in immune-related gene ***:For this study,623 samples were collected from The Cancer Genome Atlas(TCGA)database,comprising tumor mutational burden(TMB),RNA sequencing(RNA-Seq),and clinical *** gene expression analysis,Gene Ontology(GO),and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis of the identified genes were conducted using the R ***,a comparative analysis of immune infiltrating cell composition in metastatic and non-metastatic groups was *** genes,exhibiting high levels of interaction,were selected using the Search Tool for the Retrieval of Interacting Genes/proteins(STRING)*** Drug Gene interaction Database(DGIdb)was then utilized to estimate drugs targeting the identified hub ***:The transcriptome data of 326 colorectal cancer patients with low TMB were analyzed,comprising 58 patients with metastasis and 268 patients without *** the differential expression in 1,111 genes for patients with metastasis compared to those without metastasis,733 genes were upregulated,and 378 genes were *** and GO enrichment analysis indicated significant differences in gene expression in CRC metastatic patients with low TMB compared to non-metastasis patients with low *** pathways included humoral immune response,immunoglobulin production,and regulation of AMPA receptor *** genes related to interleukin-12 were identified through secondary enrichment for immune-related *** of tumor-infiltrating immune cell data revealed significant differences in memory-activated T cell CD4 and T cell ***:This analysis of RNA sequencing data and immune-filtrating cell data revealed significant differences between metastatic colorectal cancer patients with low TMB and their non-metastatic counterpa

关键词： Metastatic colorectal cancer(mCRC) RNA-seq Differentially expressed genes Functional enrichment protein-protein interaction Immunity

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Phosphorylation on TRPV4 Serine Residue 824 Enhances Its Association with PGM1

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American Journal of Molecular Biology 2016年第1期6卷 33-44页

作者： Sung Hwa Shin Eun Jeoung Lee Sunghee Hyun Sang Sun Kang Department of Biology Education Chungbuk National University Cheongju Republic of Korea Department of Internal Medicine Chungbuk National University Cheongju Republic of Korea Department of Biomedical Laboratory Science Eulji University Daejeon Republic of Korea

The TRPV4 cation channel is expressed in a broad range of tissues and participates in the generation of a Ca2+ signal and/or depolarization of membrane potential. Here, human phosphoglucomutase- 1 (PGM1), an enzyme that converts glucose-6 phosphate to glucose-1 phosphate in the glycolysis pathway, as the first auxiliary protein of TRPV4 Ca2+ channels, is identified with yeast two hybrid system, coimmunoprecipitation, confocal microscopy, and GST pull-down assays. TRPV4 forms a complex with PGM1 through its C-terminal cytoplasmic domain. Because it is demonstrated that TRPV4 serine residue 824 (S824) is phosphorylated by serum/glucocorticoid regulated kinase 1, we elucidate the effect of TRPV4 S824 phosphorylation on TRPV association with PGM1. Even an inactivated mutant version of TRPV4, S824A, exhibited a decreased ability to bind PGM1, an activated phosphomimetic mutant version of TRPV4, S824D, exhibited enhanced binding to PGM1. Thus, formation of the TRPV4/PGM1 complex and localization of this complex to the plasma membrane appear to be regulated by the phosphorylation status of residue S824 in TRPV4. The newly identified interactor of TRPV4 may help the molecular pathways modulating transport activity or glucose metabolism, respectively.

关键词： Membrane Localization Phosphoglucomutase1 Phosphorylation protein-protein interaction TRPV4

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Systems biology and OMIC data integration to understand gastrointestinal cancers

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World Journal of Clinical Oncology 2022年第10期13卷 762-778页

作者： Iasmin Moreira Costa Bispo Henry Paul Granger Palloma Porto Almeida Patricia Belini Nishiyama Leandro Martins de Freitas Núcleo de Biointegração Instituto Multidisciplinar em SaúdeUniversidade Federal da BahiaVitória da Conquista 45.029-094BahiaBrazil Division of Experimental and Translational Research Brazilian National Cancer InstituteRio de Janeiro 20231-050Brazil

Gastrointestinal(GI)cancers are a set of diverse diseases affecting many parts/*** five most frequent GI cancer types are esophageal,gastric cancer(GC),liver cancer,pancreatic cancer,and colorectal cancer(CRC);together,they give rise to 5 million new cases and cause the death of 3.5 million people *** provide information about molecular changes crucial to tumorigenesis and the behavior and *** the formation of cancer cells,the genomic changes are microsatellite instability with multiple chromosomal arrangements in GC and *** genomically stable subtype is observed in GC and pancreatic *** these genomic subtypes,CRC has epigenetic modification(hypermethylation)associated with a poor *** pathway information highlights the functions shared by GI cancers such as apoptosis;focal adhesion;and the p21-activated kinase,phosphoinositide 3-kinase/Akt,transforming growth factor beta,and Toll-like receptor signaling *** pathways show survival,cell proliferation,and cell *** addition,the immune response and inflammation are also essential elements in the shared *** also retrieved information on protein-protein interaction from the STRING database,and found that proteins Akt1,catenin beta 1(CTNNB1),E1A binding protein P300,tumor protein p53(TP53),and TP53 binding protein 1(TP53BP1)are central nodes in the *** protein expression of these genes is associated with overall survival in some GI *** low TP53BP1 expression in CRC,high EP300 expression in esophageal cancer,and increased expression of Akt1/TP53 or low CTNNB1 expression in GC are associated with a poor *** Kaplan Meier plotter database also confirmed the association between expression of the five central genes and GC survival *** conclusion,GI cancers are very diverse at the molecular ***,the shared mutations and protein pathways might be used to understand better and reveal diagnostic/prognostic or drug

关键词： Gastrointestinal cancers Genome Cellular pathways protein-protein interaction Prognosis OMIC data

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The role of exercise in modulating the HP pathway to reduce glioma-induced epilepsy

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Traditional Medicine Research 2024年第12期9卷 66-74页

作者： Fu-Jun Shi Wei Cai Nan Wu Yang Li Department of Neurosurgery Yinchuan First People’s Hospital Affiliated to Ningxia Medical UniversityYinchuan 750001China Department of Neurosurgery Tianjin Children’s HospitalTianjin 300000China

Background:Glioma-induced refractory epilepsy can be alleviated through conventional exercise,providing a potential therapeutic approach to manage this *** study aims to investigate the underlying ***:Bioinformatics methodologies were employed to scrutinize gene expression data from public repositories such as GEO,with a specific focus on mobility-related genes in *** differential and enrichment analyses,differentially expressed genes(DEGs)were identified,while protein-protein interaction networks elucidated pivotal hub ***:Our analysis revealed 32 DEGs,comprising 23 upregulated and 9 downregulated *** analysis underscored significant alterations in immune pathways in *** central hub genes,haptoglobin(HP)and prostaglandin-endoperoxide synthase 2(PTGS2),were found to be modulated by Arginase 1(ARG1)and Chemokine(C-X-C motif)ligand 8(CXCL8).GSVA analysis associated elevated PTGS2 expression with metabolic pathways,while increased HP expression was correlated with angiogenesis and *** experiments validated HP’s role in tumor cell proliferation,emphasizing its potential as a therapeutic ***:This study highlights the crucial involvement of HP and PTGS2 genes in the etiology of epilepsy,linked to discrepancies in the immune *** findings offer fresh perspectives on the management of epilepsy,emphasizing the neuroprotective possibilities of targeting specific gene pathway.

关键词： epilepsy gene expression bioinformatics immune pathways protein-protein interaction hub genes

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Human nectin-like 1, a novel membrane protein interacting with protein 4.1 R

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Progress in Natural Science:Materials International 2005年第2期 94-97页

作者： YANG Hongbo1, ZHOU Yan1, HU Xiaoyan1, XU Yaqin1, YIN Bin1, ZHU Shengtao1, FAN Wenhong2, FAN Ming2, QIANG Boqin1, YUAN Jiangang1 and PENG Xiaozhong1*(1. National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100005, China 2. Department of Neurobiology, Institute of Basic Medical Science, Academy of Military Medical Sciences, Beijing 100850, China)

Human nectin-like 1 (NECL1) full-length cDNA was cloned by bioinformatics method when searching for candidate membrane proteins interacting with members of protein 4.1 family. The cytoplasmic and extracellular regions of NECL1 were expressed in and purified from ***, and the polyclonal antibody was produced. interaction between the cytoplasmic region of NECL1 and the 30 kD membrane binding domain of protein 4.1 on red blood cell (4.1R) was demonstrated by IAsys-biosensor system and GST pull-down experiment. Results of biotin-labeled peptide ELISA further demonstrated the key amino acids for the binding. The interaction research of NECL1's cytoplasmic domain provides basis for further study of the functions of NECL1 in nervous system.

关键词： nectin-like 1 protein-protein interaction protein 4.1 R.

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A Review on the Pathogenicity of Cucumber Mosaic Virus

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Agricultural Biotechnology 2018年第1期7卷 87-91页

作者： Yanhong QIU Chaonan WANG Shuifang ZHU Institute of Plant Quarantine Chinese Academy of Inspection and Quarantine College of Plant Protection China Agricultural University

Cucumber mosaic virus （CMV）, a positive-sense single-stranded RNA virus, has a very wide host range and a worldwide distribution, and is considered as one of the most virulent plant viruses in the world. The CMV gene sequences, gene products, and their interaction with hosts have been extensively reported since it was discovered in 1916. With the development of high-throughput sequencing and proteomics, great progress has been made in the molecular mechanism of CMV pathogenesis in recent years. In this review, we introduce CMV-encoded proteins, CMV-related satellite RNAs and the roles of host factors in the pathogenesis of CMV, to provide a theoretical basis for future study of CMV.

关键词： Cucumber mosaic virus (CMV) Pathogenic mechanism Small interfering RNA protein-protein interaction

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