Differentially expressed genes reveal adaptations between free-living and symbiotic niches of Vibrio fischeri in a fully established mutualism

A major force driving in the innovation of mutualistic symbioses is the number of adaptations that both organisms must acquire to provide overall increased fitness for a successful partnership. Many of these symbioses are relatively dependent on the ability of the symbiont to locate a host (specificity), as well as provide some novel capability upon colonization. The mutualism between sepiolid squids and members of the Vibrionaceae is a unique system in which development of the symbiotic partnership has been studied in detail, but much remains unknown about the genetics of symbiont colonization and persistence within the host. Using a method that captures exclusively expressed transcripts in either free-living or host-associated strains of Vibrio fischeri, we identified and verified expression of genes differentially expressed in both states from two symbiotic strains of V. fischeri. These genes provide a glimpse into the microhabitat V. fischeri encounters in both free-living seawater and symbiotic host light organ-associated habitats, providing insight into the elements necessary for local adaptation and the evolution of host specificity in this unique mutualism.Key words: Vibrionaceae, gene expression, Sepiolidae, Euprymna, SCOTS.

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Gene Expression Profiling of Hyperdiploid Multiple Reveal Complex Gene Dosage Effects and an mRNA Translation/Protein Synthesis Signature.

Blood ◽

10.1182/blood.v106.11.1538.1538 ◽

2005 ◽

Vol 106 (11) ◽

pp. 1538-1538

Author(s):

Wee-Joo Chng ◽

Scott Van Wier ◽

Gregory Ahmann ◽

Tammy Price-Troska ◽

Kim Henderson ◽

...

Keyword(s):

Gene Expression ◽

Protein Synthesis ◽

Differentially Expressed Genes ◽

Gene Dosage ◽

Gene Copy Number ◽

Mrna Translation ◽

Differentially Expressed ◽

Gene Copy ◽

Gene Dosage Effect ◽

Expression Of Genes

Abstract Hyperdiploid MM (H-MM), characterized by recurrent trisomies constitute about 50% of MM, yet very little is known about its pathogenesis and oncogenic mechanisms. Studies in leukemia and solid tumors have shown gene dosage effect of aneuploidy on gene expression. To determine the possible gene dosage effect and deregulated cellular program in H-MM we undertook a gene expression study of CD138-enriched plasma-cell RNA from 53 hyperdiploid and 37 non-hyperdiploid MM (NH-MM) patients using the Affymetrix U133A chip (Affymetrix, Santa Clara, CA). Gene expression data was analyzed using GeneSpring 7 (Agilent Technologies, Palo Alto, CA). Genes differentially expressed between H-MM and NH-MM were obtained by t-test (p<0.01). The majority of the differentially expressed genes (57%) were under-expressed in H-MM. Genes located on the commonly trisomic chromosomes were mostly (but not always) over-expressed in H-MM and constitute 76% of over-expressed genes. Chromosome 1 contained the most differentially expressed genes (17%) followed by chromosome 12 (9%), and 19 (8%). To examine the relationship of gene copy number to gene expression, we examined the expression of genes on chromosomes 9 and 15 in subjects with 2 copies (15 normal control and 20 NH-MM) and 3 copies (12 H-MM) of each chromosome as detected by interphase FISH. We then derived a ratio of the mean expression of each gene on these chromosomes between patients with 3 copies and 2 copies of the chromosome. If a simple relationship exists between gene expression and gene copy number, one would expect the ratio of expression of most genes on these two chromosomes to be about 1.5 in H-MM compared to NH-MM. However, many genes have ratios either higher than 2 or lower than 0.5. Furthermore, when the heterogeneity of cells with underlying trisomies is taken into consideration by correcting the ratio for the number of cells with trisomies, the actual ratio is always lower than the expected ratio. When the expression of genes on a chromosome was compressed to a median value, this value was always higher in the trisomic chromosomes for H-MM compared to NH-MM. The data suggests that although gene dosage influence gene expression, the relationship is complex and some genes are more gene dosage dependent than others. Amongst the differentially expressed genes with known function, 33% are involved in mRNA translation/protein synthesis. Of note, 37 of the top 100 differentially expressed genes are involved in these processes. In particular, 60 ribosomal protein (RP) genes are significantly (p<0.05) upregulated in H-MM. This signature in H-MM is not associated with increase proliferation as measured by PCLI. This predominant signature suggests that deregulated protein synthesis may be important for the biology of H-MM. Many of these RPs are involved in the synthesis of product of oncogenic pathways (e.g. MYC, NF-KB pathways) and may mediate the growth and survival of tumor cells. It is therefore possible that these tumor cells may be sensitive to the disruption of mRNA translation/protein synthesis. Targeting the mTOR pathway with rapamycin may therefore be useful for treatment of H-MM.

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Selenium Regulates Gene Expression for Glucosinolate and Carotenoid Biosynthesis in Arabidopsis

Journal of the American Society for Horticultural Science ◽

10.21273/jashs.136.1.23 ◽

2011 ◽

Vol 136 (1) ◽

pp. 23-34 ◽

Cited By ~ 22

Author(s):

Carl E. Sams ◽

Dilip R. Panthee ◽

Craig S. Charron ◽

Dean A. Kopsell ◽

Joshua S. Yuan

Keyword(s):

Gene Expression ◽

Differentially Expressed Genes ◽

Plant Species ◽

Chlorophyll Biosynthesis ◽

Plant Secondary Metabolites ◽

Carotenoid Biosynthesis ◽

Differentially Expressed ◽

Biosynthesis Pathway ◽

Tissue Samples ◽

Expression Of Genes

Glucosinolates (GSs) and carotenoids are important plant secondary metabolites present in several plant species, including arabidopsis (Arabidopsis thaliana). Although genotypic and environmental regulation of GSs and carotenoid compounds has been reported, few studies present data on their regulation at the molecular level. Therefore, the objective of this study was to explore differential expression of genes associated with GSs and carotenoids in arabidopsis in response to selenium fertilization, shown previously to impact accumulations of both classes of metabolites in Brassica species. Arabidopsis was grown under 0.0 or 10.0 μM Na2SeO4 in hydroponic culture. Shoot and root tissue samples were collected before anthesis to measure GSs and carotenoid compounds and conduct gene expression analysis. Gene expression was determined using arabidopsis oligonucleotide chips containing more than 31,000 genes. There were 1274 differentially expressed genes in response to selenium (Se), of which 516 genes were upregulated. Ontology analysis partitioned differentially expressed genes into 20 classes. Biosynthesis pathway analysis using AraCyc revealed that four GSs, one carotenoid, and one chlorophyll biosynthesis pathways were invoked by the differentially expressed genes. Involvement of the same gene in more than one biosynthesis pathway indicated that the same enzyme may be involved in multiple GS biosynthesis pathways. The decrease in carotenoid biosynthesis under Se treatment occurred through the downregulation of phytoene synthase at the beginning of the carotenoid biosynthesis pathway. These findings may be useful to modify the GS and carotenoid levels in arabidopsis and may lead to modification in agriculturally important plant species.

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Changes in Differential Gene and Protein Expression Patterns during Development of Cord Blood (CB) Versus Adult Peripheral Blood (APB) Monocyte (Mo) into Mature Dendritic Cells (mDC): Insight into Immaturity of CB DC Immunity.

Blood ◽

10.1182/blood.v108.11.5204.5204 ◽

2006 ◽

Vol 108 (11) ◽

pp. 5204-5204

Author(s):

Hong Jiang ◽

Cheryl Wade-Harris ◽

Megan Lim ◽

Laxmi Baxi ◽

Mitchell S. Cairo

Keyword(s):

Gene Expression ◽

Differentially Expressed Genes ◽

Developmental Stages ◽

Expression Patterns ◽

Oligonucleotide Microarray ◽

Differentially Expressed ◽

Expression Of Genes ◽

Differential Gene ◽

Hla Dqa1 ◽

Antigen Presenting

Abstract It has been recognized that dysfunction of CB immune system is in part due to the immaturity of CB cellular immunity (Cairo, Blood,1997). The molecular mechanisms associated with the immaturity of CB cellular immunity including DC subset remain to be defined. The maturation status of DC greatly influences its antigen presentation capacity. Recently, we have utilized oligonucleotide microarray to demonstrate differential gene expression profiles of CB vs APB Mo (Jiang/Cairo, JI, 2004). In the current study, differential expressed genes and proteins were examined in Mo-derived CB vs. APB DC during DC developmental stages: Mo, immature DC (iDC) and mDC, by utilizing oligonucleotide microarray and proteomics. Briefly, Mo isolated from CB or APB and cultured for 8 days with GM-CSF/IL-4 (iDC) and further stimulated with LPS (mDC). Oligonucleotide microarray was carried out using U133A gene chip (Affymetrix). The representative differentially expressed genes resulted from microarray analysis were selected and analyzed by quantitative RT-PCR (Roche). The proteomic technique was conducted by liquid chromatography (LC) and mass spectrometry (MS) (Lim, Mol Cell Proteomics, 2006). The differentially expressed proteins were compared in CB vs. APB for iDC and mDC. We identified different gene expression patterns that were significantly lower in CB vs. APB in different stages during DC differentiation: Mo, iDC and mDC. These differentially expressed genes included RELA (5F), JUNB (6F), IRF-1 (3F) in Mo; CREB5 (3F), MAP7 (5F), IL1R2 (6F) in iDC; and HLA-DQA1 (4F), CD80 (3F), IRF-5 (3F) in mDC. The proteomic studies demonstrated Tyrosine Kinase Fer (12.5F), Actin regulator 3 (2.5F), Rap guanine nucleotide exchange factor 1 (2.4F) and Myeloid cell nuclear differentiation antigen (1.5F) were expressed higher in APB vs.CB iDC, while MAX binding protein MNT (5.5F), IRS2 (2.2F) and Zinc-Finger Proteins (514, 212, 462) (3–14F) were expressed higher in CB vs. APB iDC. Further, the proteomic results also indicated other Zinc-Finger Proteins (292, 221, 474) (2–5F), Fibrillin 1 precursor (2.5F) and interleukin-4 (7.7F) were expressed higher in APB vs. CB mDC. In contrast, cyclin I (3F), Rb-like protein 2 (4.35 F) and PKC theta (2F) were significantly lower in APB vs. CB DC. Moreover, the comparison of CB vs. APB DC antigen presenting activity by ELISPOT was performed and the influenza-peptide loaded CB-mDC demonstrated weaker ability to induce T cells to produce IFNg compared with APB-mDC. In summary, these differentially expressed genes in Mo (RELA, JUN) may play key roles in initiating Mo differentiation toward DC. The increased expression of genes in APB vs. CB iDC, like CREB5, IL1R2, may be involved in mediating maturation process of iDC to mDC. Lastly, the elevated expression of genes in APB vs. CB mDC, such as HLA-DQA1, CD80, IRF5 among others, may be likely to control mDC functionality as demonstrated by weaker antigen presenting activity of CB vs. APB mDC. We postulate that decreased expression of specific genes in CB vs. APB DC during DC developmental stages may in part be responsible for the lack of maturity of CB, and ultimately may partially be responsible for differential CB vs. APB innate and adaptive immunity.

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Differentially expressed genes reflect disease-induced rather than disease-causing changes in the transcriptome

10.1101/2020.10.19.20213538 ◽

2020 ◽

Author(s):

Eleonora Porcu ◽

Marie C. Sadler ◽

Kaido Lepik ◽

Chiara Auwerx ◽

Andrew R. Wood ◽

...

Keyword(s):

Gene Expression ◽

Differentially Expressed Genes ◽

Whole Blood ◽

Complex Traits ◽

Causal Effects ◽

Differentially Expressed ◽

Polygenic Risk Score ◽

Transcript Levels ◽

Expression Of Genes ◽

Shed Light

AbstractComparing transcript levels between healthy and diseased individuals allows the identification of differentially expressed genes, which may be causes, consequences or mere correlates of the disease under scrutiny. Here, we propose a bi-directional Transcriptome-Wide Mendelian Randomization (TWMR) approach that integrates summary-level data from GWAS and whole-blood eQTLs in a MR framework to investigate the causal effects between gene expression and complex traits.Whereas we have previously developed a TWMR approach to elucidate gene expression to trait causal effects, here we are adapting the method to shed light on the causal imprint of complex traits on transcript levels. We termed this new approach reverse TWMR (revTWMR). Integrating bi-directional causal effects between gene expression and complex traits enables to evaluate their respective contributions to the correlation between gene expression and traits. We uncovered that whole blood gene expression-trait correlation is mainly driven by causal effect from the phenotype on the expression rather than the reverse. For example, BMI- and triglycerides-gene expression correlation coefficients robustly correlate with trait-to-expression causal effects (r=0.09, P=1.54×10−39 and r=0.09, P=1.19×10−34, respectively), but not detectably with expression-to-trait effects.Genes implicated by revTWMR confirmed known associations, such as rheumathoid arthritis and Crohn’s disease induced changes in expression of TRBV and GBP2, respectively. They also shed light on how clinical biomarkers can influence their own levels. For instance, we observed that high levels of high-density lipoprotein (HDL) cholesterol lowers the expression of genes involved in cholesterol biosynthesis (SQLE, FDFT1) and increases the expression of genes responsible for cholesterol efflux (ABCA1, ABCG1), two key molecular pathways in determining HDL levels. Importantly, revTWMR is more robust to pleiotropy than polygenic risk score (PRS) approaches which can be misled by pleiotropic outliers. As one example, revTWMR revealed that the previously reported association between educational attainment PRS and STX1B is exclusively driven by a highly pleiotropic SNP (rs2456973), which is strongly associated with several hematological and anthropometric traits.In conclusion, our method disentangles the relationship between gene expression and phenotypes and reveals that complex traits have more pronounced impact on gene expression than the reverse. We demonstrated that studies comparing the transcriptome of diseased and healthy subjects are more prone to reveal disease-induced gene expression changes rather than disease causing ones.

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Effect of Differential Expression of Genes Induced by Radiation Therapy In Cancer-associated fibroblasts Cell on Patients' Prognosis

10.21203/rs.3.rs-30037/v1 ◽

2020 ◽

Author(s):

Jiasheng Xu ◽

Kaili Liao ◽

Han Nie ◽

Danni Xue ◽

Xiaozhong Wang

Keyword(s):

Gene Expression ◽

Radiation Therapy ◽

Differential Expression ◽

Differentially Expressed Genes ◽

Protein Interaction ◽

Differentially Expressed ◽

Hub Genes ◽

Value Analysis ◽

Expression Of Genes ◽

Differential Expression Of Genes

Abstract To investigate the effect of radiation therapy on differential expression of genes in tumor-associated fibroblasts and prognosis of patients.Methods: The tumor-associated fibroblast gene expression profile data chip GSE37318 after radiotherapy treatment was retrieved from the GEO database, and the differentially expressed genes were screened using the limma R software package; GO and KEGG pathway enrichment analysis was performed using the DAVID tool; Protein interaction networks was built by String and Cytoscape software and core genes were obtained; GEPIA was used for prognostic value analysis; Immunohistochemistry was used to detect the expression of the top 5 hub genes in tumor tissues of patients in the radiotherapy and non-radiotherapy groups.Results: 144 genes were up-regulated and 54 genes were down-regulated, which were mainly enriched in functional pathways such as cell stress, DNA damage, cell cycle, aging, apoptosis, oxidative stress, and p53 signaling pathway. The protein interaction network was constructed and the top 20 hub genes were obtained. Prognostic analysis showed that: Expression of up-regulated PCNA and hub genes that were down-regulated after irradiation, such as MCM10, DLGAP5, FANCI, CENPA, CDC6, FBXO5, NCAPG, and DTL, has a negative correlation with the overall survival time of lung cancer patients (p <0.05). Immunohistochemical results showed that PCNA gene expression was up-regulated in patients with radiotherapy compared with patients without radiotherapy. The test results are consistent with the results of the biochemical analysis.Conclusion: Radiotherapy can induce differential expression of genes in tumor-associated fibroblasts, and these differentially expressed genes can be used as potential molecular markers for tumor radiotherapy effect and patient prognosis.

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Chromosomal neighbourhoods allow identification of organ specific changes in gene expression

PLoS Computational Biology ◽

10.1371/journal.pcbi.1008947 ◽

2021 ◽

Vol 17 (9) ◽

pp. e1008947

Author(s):

Rishi Das Roy ◽

Outi Hallikas ◽

Mona M. Christensen ◽

Elodie Renvoisé ◽

Jukka Jernvall

Keyword(s):

Gene Expression ◽

Differential Expression ◽

Differentially Expressed Genes ◽

Tooth Development ◽

Differentially Expressed ◽

Protein Coding ◽

Functional Roles ◽

Expression Of Genes ◽

Organ Specific ◽

Molar Teeth

Although most genes share their chromosomal neighbourhood with other genes, distribution of genes has not been explored in the context of individual organ development; the common focus of developmental biology studies. Because developmental processes are often associated with initially subtle changes in gene expression, here we explored whether neighbouring genes are informative in the identification of differentially expressed genes. First, we quantified the chromosomal neighbourhood patterns of genes having related functional roles in the mammalian genome. Although the majority of protein coding genes have at least five neighbours within 1 Mb window around each gene, very few of these neighbours regulate development of the same organ. Analyses of transcriptomes of developing mouse molar teeth revealed that whereas expression of genes regulating tooth development changes, their neighbouring genes show no marked changes, irrespective of their level of expression. Finally, we test whether inclusion of gene neighbourhood in the analyses of differential expression could provide additional benefits. For the analyses, we developed an algorithm, called DELocal that identifies differentially expressed genes by comparing their expression changes to changes in adjacent genes in their chromosomal regions. Our results show that DELocal removes detection bias towards large changes in expression, thereby allowing identification of even subtle changes in development. Future studies, including the detection of differential expression, may benefit from, and further characterize the significance of gene-gene neighbour relationships.

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Differential gene expression analysis of ankylosing spondylitis shows deregulation of the HLA-DRB, HLA-DQB, ITM2A, and CTLA4 genes

Egyptian Journal of Medical Human Genetics ◽

10.1186/s43042-021-00161-0 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Rowan AlEjielat ◽

Anas Khaleel ◽

Amneh H. Tarkhan

Keyword(s):

Gene Expression ◽

Ankylosing Spondylitis ◽

Differentially Expressed Genes ◽

Gene Network ◽

Disease Diagnosis ◽

Receptor Activation ◽

Functional Enrichment ◽

Differentially Expressed ◽

Inflammatory Disorder ◽

Data Set

Abstract Background Ankylosing spondylitis (AS) is a rare inflammatory disorder affecting the spinal joints. Although we know some of the genetic factors that are associated with the disease, the molecular basis of this illness has not yet been fully elucidated, and the genes involved in AS pathogenesis have not been entirely identified. The current study aimed at constructing a gene network that may serve as an AS gene signature and biomarker, both of which will help in disease diagnosis and the identification of therapeutic targets. Previously published gene expression profiles of 16 AS patients and 16 gender- and age-matched controls that were profiled on the Illumina HumanHT-12 V3.0 Expression BeadChip platform were mined. Patients were Portuguese, 21 to 64 years old, were diagnosed based on the modified New York criteria, and had Bath Ankylosing Spondylitis Disease Activity Index scores > 4 and Bath Ankylosing Spondylitis Functional Index scores > 4. All patients were receiving only NSAIDs and/or sulphasalazine. Functional enrichment and pathway analysis were performed to create an interaction network of differentially expressed genes. Results ITM2A, ICOS, VSIG10L, CD59, TRAC, and CTLA-4 were among the significantly differentially expressed genes in AS, but the most significantly downregulated genes were the HLA-DRB6, HLA-DRB5, HLA-DRB4, HLA-DRB3, HLA-DRB1, HLA-DQB1, ITM2A, and CTLA-4 genes. The genes in this study were mostly associated with the regulation of the immune system processes, parts of cell membrane, and signaling related to T cell receptor and antigen receptor, in addition to some overlaps related to the IL2 STAT signaling, as well as the androgen response. The most significantly over-represented pathways in the data set were associated with the “RUNX1 and FOXP3 which control the development of regulatory T lymphocytes (Tregs)” and the “GABA receptor activation” pathways. Conclusions Comprehensive gene analysis of differentially expressed genes in AS reveals a significant gene network that is involved in a multitude of important immune and inflammatory pathways. These pathways and networks might serve as biomarkers for AS and can potentially help in diagnosing the disease and identifying future targets for treatment.

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Behavioral sensitization induced by methamphetamine causes differential alterations in gene expression and histone acetylation of the prefrontal cortex in rats

BMC Neuroscience ◽

10.1186/s12868-021-00616-5 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Hui Li ◽

Jing-An Chen ◽

Qian-Zhi Ding ◽

Guan-Yi Lu ◽

Ning Wu ◽

...

Keyword(s):

Gene Expression ◽

Prefrontal Cortex ◽

Histone Acetylation ◽

Differentially Expressed Genes ◽

Behavioral Sensitization ◽

Functional Enrichment ◽

Differentially Expressed ◽

Adult Rats ◽

Mrna Microarray ◽

H3 Acetylation

Abstract Background Methamphetamine (METH) is one of the most widely abused illicit substances worldwide; unfortunately, its addiction mechanism remains unclear. Based on accumulating evidence, changes in gene expression and chromatin modifications might be related to the persistent effects of METH on the brain. In the present study, we took advantage of METH-induced behavioral sensitization as an animal model that reflects some aspects of drug addiction and examined the changes in gene expression and histone acetylation in the prefrontal cortex (PFC) of adult rats. Methods We conducted mRNA microarray and chromatin immunoprecipitation (ChIP) coupled to DNA microarray (ChIP-chip) analyses to screen and identify changes in transcript levels and histone acetylation patterns. Functional enrichment analyses, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, were performed to analyze the differentially expressed genes. We then further identified alterations in ANP32A (acidic leucine-rich nuclear phosphoprotein-32A) and POU3F2 (POU domain, class 3, transcription factor 2) using qPCR and ChIP-PCR assays. Results In the rat model of METH-induced behavioral sensitization, METH challenge caused 275 differentially expressed genes and a number of hyperacetylated genes (821 genes with H3 acetylation and 10 genes with H4 acetylation). Based on mRNA microarray and GO and KEGG enrichment analyses, 24 genes may be involved in METH-induced behavioral sensitization, and 7 genes were confirmed using qPCR. We further examined the alterations in the levels of the ANP32A and POU3F2 transcripts and histone acetylation at different periods of METH-induced behavioral sensitization. H4 hyperacetylation contributed to the increased levels of ANP32A mRNA and H3/H4 hyperacetylation contributed to the increased levels of POU3F2 mRNA induced by METH challenge-induced behavioral sensitization, but not by acute METH exposure. Conclusions The present results revealed alterations in transcription and histone acetylation in the rat PFC by METH exposure and provided evidence that modifications of histone acetylation contributed to the alterations in gene expression caused by METH-induced behavioral sensitization.

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Impact of aging on gene expression response to x-ray irradiation using mouse blood

Scientific Reports ◽

10.1038/s41598-021-89682-7 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Constantinos G. Broustas ◽

Axel J. Duval ◽

Sally A. Amundson

Keyword(s):

Gene Expression ◽

Differentially Expressed Genes ◽

Differentially Expressed ◽

X Rays ◽

Gene Expression Response ◽

X Ray ◽

The Impact ◽

Old Mice ◽

Radiation Biodosimetry ◽

Young Mice

AbstractAs a radiation biodosimetry tool, gene expression profiling is being developed using mouse and human peripheral blood models. The impact of dose, dose-rate, and radiation quality has been studied with the goal of predicting radiological tissue injury. In this study, we determined the impact of aging on the gene expression profile of blood from mice exposed to radiation. Young (2 mo) and old (21 mo) male mice were irradiated with 4 Gy x-rays, total RNA was isolated from whole blood 24 h later, and subjected to whole genome microarray analysis. Pathway analysis of differentially expressed genes revealed young mice responded to x-ray exposure by significantly upregulating pathways involved in apoptosis and phagocytosis, a process that eliminates apoptotic cells and preserves tissue homeostasis. In contrast, the functional annotation of senescence was overrepresented among differentially expressed genes from irradiated old mice without enrichment of phagocytosis pathways. Pathways associated with hematologic malignancies were enriched in irradiated old mice compared with irradiated young mice. The fibroblast growth factor signaling pathway was underrepresented in older mice under basal conditions. Similarly, brain-related functions were underrepresented in unirradiated old mice. Thus, age-dependent gene expression differences should be considered when developing gene signatures for use in radiation biodosimetry.

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Construction of a competitive endogenous RNA network and analysis of potential regulatory axis targets in glioblastoma

Cancer Cell International ◽

10.1186/s12935-021-01789-z ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Kai Yu ◽

Huan Yang ◽

Qiao-li Lv ◽

Li-chong Wang ◽

Zi-long Tan ◽

...

Keyword(s):

Gene Expression ◽

Overall Survival ◽

Differentially Expressed Genes ◽

Pearson Correlation ◽

Differentially Expressed ◽

Migration And Invasion ◽

Glioblastoma Cells ◽

Network Chain ◽

Cerna Network ◽

Potential Marker

Abstract Background Glioblastoma is the most common primary malignant brain tumor. Because of the limited understanding of its pathogenesis, the prognosis of glioblastoma remains poor. This study was conducted to explore potential competing endogenous RNA (ceRNA) network chains and biomarkers in glioblastoma by performing integrated bioinformatics analysis. Methods Transcriptome expression data from The Cancer Genome Atlas database and Gene Expression Omnibus were analyzed to identify differentially expressed genes between glioblastoma and normal tissues. Biological pathways potentially associated with the differentially expressed genes were explored by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis, and a protein-protein interaction network was established using the STRING database and Cytoscape. Survival analysis using Gene Expression Profiling Interactive Analysis was based on the Kaplan–Meier curve method. A ceRNA network chain was established using the intersection method to align data from four databases (miRTarBase, miRcode, TargetScan, and lncBace2.0), and expression differences and correlations were verified by quantitative reverse-transcription polymerase chain reaction analysis and by determining the Pearson correlation coefficient. Additionally, an MTS assay and the wound-healing and transwell assays were performed to evaluate the effects of complement C1s (C1S) on the viability and migration and invasion abilities of glioblastoma cells, respectively. Results We detected 2842 differentially expressed (DE) mRNAs, 2577 DE long non-coding RNAs (lncRNAs), and 309 DE microRNAs (miRNAs) that were dysregulated in glioblastoma. The final ceRNA network consisted of six specific lncRNAs, four miRNAs, and four mRNAs. Among them, four DE mRNAs and one DE lncRNA were correlated with overall survival (p < 0.05). C1S was significantly correlated with overall survival (p= 0.015). In functional assays, knockdown of C1S inhibited the proliferation and invasion of glioblastoma cell lines. Conclusions We established four ceRNA networks that may influence the occurrence and development of glioblastoma. Among them, the MIR155HG/has-miR-129-5p/C1S axis is a potential marker and therapeutic target for glioblastoma. Knockdown of C1S inhibited the proliferation, migration, and invasion of glioblastoma cells. These findings clarify the role of the ceRNA regulatory network in glioblastoma and provide a foundation for further research.

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