Comprehensive bioinformatics analysis of mRNA expression profiles and identification of a miRNA–mRNA network associated with lupus nephritis

Lupus ◽  
2020 ◽  
Vol 29 (8) ◽  
pp. 854-861
Author(s):  
Jianbo Song ◽  
Liqin Zhao ◽  
Yuanping Li

Objective Lupus nephritis (LN) is one of the serious complications of systemic lupus erythematosus. The aim of this study was to identify core genes and pathways involved in the pathogenesis of LN. Methods We screened differentially expressed genes (DEGs) in LN patients using mRNA expression profile data from the Gene Expression Omnibus. The functional and pathway enrichment analysis of DEGs was performed utilizing the Database for annotation, Visualization and Integrated Discovery. Target genes with differentially expressed miRNAs (DEMIs) were predicted using the miRTarBase database, and the intersection between these target genes and DEGs was selected to be studied further. Results In total, 107 common DEGs (CDEGs) were identified from the Tub_LN group and Glom_LN group, and 66 DEMIs were identified. Fifty-three hub genes and two significant modules were identified from the protein–protein interaction (PPI) network, and a miRNA–mRNA network was constructed. The CDEGs, module genes in the PPI network and genes intersecting with the CDEGs and target genes of DEMIs were all associated with the PI3K-Akt signalling pathway. Conclusion In summary, this study reveals some crucial genes and pathways potentially involving in the pathogenesis of LN. These findings provide a new insight for the research and treatment of LN.

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Guangyu Gao ◽  
Zhen Yao ◽  
Jiaofeng Shen ◽  
Yulong Liu

Dabrafenib resistance is a significant problem in melanoma, and its underlying molecular mechanism is still unclear. The purpose of this study is to research the molecular mechanism of drug resistance of dabrafenib and to explore the key genes and pathways that mediate drug resistance in melanoma. GSE117666 was downloaded from the Gene Expression Omnibus (GEO) database and 492 melanoma statistics were also downloaded from The Cancer Genome Atlas (TCGA) database. Besides, differentially expressed miRNAs (DEMs) were identified by taking advantage of the R software and GEO2R. The Database for Annotation, Visualization, and Integrated Discovery (DAVID) and FunRich was used to perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis to identify potential pathways and functional annotations linked with melanoma chemoresistance. 9 DEMs and 872 mRNAs were selected after filtering. Then, target genes were uploaded to Metascape to construct protein-protein interaction (PPI) network. Also, 6 hub mRNAs were screened after performing the PPI network. Furthermore, a total of 4 out of 9 miRNAs had an obvious association with the survival rate ( P < 0.05 ) and showed a good power of risk prediction model of over survival. The present research may provide a deeper understanding of regulatory genes of dabrafenib resistance in melanoma.


2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Qiaowei Fan ◽  
Lin Guo ◽  
Jingming Guan ◽  
Jing Chen ◽  
Yujing Fan ◽  
...  

Purpose. Gegen Qinlian decoction (GQD) has been used to treat gastrointestinal diseases, such as diarrhea and ulcerative colitis (UC). A recent study demonstrated that GQD enhanced the effect of PD-1 blockade in colorectal cancer (CRC). This study used network pharmacology analysis to investigate the mechanisms of GQD as a potential therapeutic approach against CRC. Materials and Methods. Bioactive chemical ingredients (BCIs) of GQD were collected from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. CRC-specific genes were obtained using the gene expression profile GSE110224 from the Gene Expression Omnibus (GEO) database. Target genes related to BCIs of GQD were then screened out. The GQD-CRC ingredient-target pharmacology network was constructed and visualized using Cytoscape software. A protein-protein interaction (PPI) network was subsequently constructed and analyzed with BisoGenet and CytoNCA plug-in in Cytoscape. Gene Ontology (GO) functional and the Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment analysis for target genes were then performed using the R package of clusterProfiler. Results. One hundred and eighteen BCIs were determined to be effective on CRC, including quercetin, wogonin, and baicalein. Twenty corresponding target genes were screened out including PTGS2, CCNB1, and SPP1. Among these genes, CCNB1 and SPP1 were identified as crucial to the PPI network. A total of 212 GO terms and 6 KEGG pathways were enriched for target genes. Functional analysis indicated that these targets were closely related to pathophysiological processes and pathways such as biosynthetic and metabolic processes of prostaglandins and prostanoids, cytokine and chemokine activities, and the IL-17, TNF, Toll-like receptor, and nuclear factor-kappa B (NF-κB) signaling pathways. Conclusion. The study elucidated the “multiingredient, multitarget, and multipathway” mechanisms of GQD against CRC from a systemic perspective, indicating GQD to be a candidate therapy for CRC treatment.


2020 ◽  
Author(s):  
Sheng Chang ◽  
Yang Cao

Abstract Background: Osteosarcoma (osteogenic sarcoma, OS) is a primary cause of morbidity and mortality and is associated with poor prognosis in the field of orthopedic. Globally, rates of OS are highest among 15 to 25-year-old adolescent. However, the mechanism of gene regulation and signaling pathway is unknown. Material and Methods: GSE9508, including 34 OS samples and 5 non-malignant bone samples, was gained from Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were picked out by GEO2R online R soft tool. Furthermore, the protein-protein interaction (PPI) network between the DEGs was molded utilizing STRING online software. Afterward, PPI network of DEGs was constructed. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of DEGs were carried out on DAVID online tool and visualized via cytoscape software. Subsequently, module analysis of PPI was performed by using MCODE app. What’s more, prognosis-related genes were screened by using online databases including GEPIA, UALCAN and cBioPortal databases. Results: Totally, 671 DEGs were picked out, including 501 up-regulated genes and 170 down-regulated genes. Moreover, 22 hub genes were identified to be significantly expressed in PPI network (16 up-regulated and 6 down-regulated). We found that spliceosome signaling pathway may provide a potential target in OS. Furthermore, on the basis of common crucial pathway, PRPF38A and SNRPC were closely associated with spliceosome. Conclusion: This study showed that SNRPC and PRPF38A are potential biomarkers candidates for osteosarcoma.


2020 ◽  
Author(s):  
Kainan Lin ◽  
Zhenyan Pan ◽  
Renke He ◽  
Hanchu Wang ◽  
Kai Zhou ◽  
...  

Abstract Purpose: Endometriosis was a common gynecological disease, however, the specific mechanism and the key molecules of endometriosis remained uncertain. This study aimed to single out key genes associated with poor prognosis, and further uncover underlying mechanisms.Methods: Data regarding mRNA expression profiles used in this study were retrieved from the Gene Expression Omnibus (GEO) database, a total of three mRNA expression profiles were included for subsequent analysis (GSE31515, GSE58178 and GSE120103). Then, we conducted Gene Ontology analysis (GO analysis), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and protein-protein interaction (PPI) analysis by the software R.Results: A total of 304 differentially expressed genes (DEGs) between endometriosis tissues and normal endometrium tissues were identified in integrated analysis, including 185 up-regulated genes and 119 down-regulated genes. GO analysis reveals that the DEGs of endometriosis were closely associated with molecular origin of bacteria. KEGG pathway enrichment analysis indicates that the DEGs were mainly involved in AGE-RAGE signaling pathway in diabetic complications. In addition, PPI of these DEGs was visualized by Cytoscape platform with utilization of Search Tool for the Retrieval of Interacting Genes (STRING). PPI analysis identifies 10 potential DEGs-related protein targets, including CCND1, IL6, CCL2, COL1A2, PTGS2, VCAM1, COL3A1, ELN, SERPINE1, HSP90B1. Conclusion: In conclusion, the present study reveals that bacterial contamination, defect of female reproductive system development, retrograde menstruation and the AGE-RAGE signaling pathway may be involved in the development of endometriosis In addition, these identified DEGs may be of clinical significance for the diagnosis and treatment of the endometriosis.


2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Zhi Lv ◽  
Liping Sun ◽  
Qian Xu ◽  
Chengzhong Xing ◽  
Yuan Yuan

Abstract Background N6-methyladenosine (m6A) modification might be closely associated with the genesis and development of gastric cancer (GC). Currently, the evidence established by high-throughput assay for GC-related m6A patterns based on long non-coding RNAs (lncRNAs) remains limited. Here, a joint analysis of lncRNA m6A methylome and lncRNA/mRNA expression profiles in GC was performed to explore the regulatory roles of m6A modification in lncRNAs. Methods Three subjects with primary GC were enrolled in our study and paired sample was randomly selected from GC tissue and adjacent normal tissue for each case. Methylated RNA Immunoprecipitation NextGeneration Sequencing (MeRIP-Seq) and Microarray Gene Expression Profiling was subsequently performed. Then co-expression analysis and gene enrichment analysis were successively conducted. Results After data analysis, we identified 191 differentially m6A-methylated lncRNAs, 240 differentially expressed lncRNAs and 229 differentially expressed mRNAs in GC. Furthermore, four differentially m6A-methylated and expressed lncRNAs (dme-lncRNAs) were discovered including RASAL2-AS1, LINC00910, SNHG7 and LINC01105. Their potential target genes were explored by co-expression analysis. And gene enrichment analysis suggested that they might influence the cellular processes and biological behaviors involved in mitosis and cell cycle. The potential impacts of these targets on GC cells were further validated by CCLE database and literature review. Conclusions Four novel dme-lncRNAs were identified in GC, which might exert regulatory roles on GC cell proliferation. The present study would provide clues for the lncRNA m6A methylation-based research on GC epigenetic etiology and pathogenesis.


2018 ◽  
Vol 2018 ◽  
pp. 1-6 ◽  
Author(s):  
Lai-Te Chen ◽  
Chen-Yang Jiang

In order to identify potential biomarkers that distinguish the embolic stroke (ES) from thrombotic stroke (TS), a profile of microRNA expression was analyzed. The GSE60319 expression profile was downloaded from the Gene Expression Omnibus (GEO) database. The GEO2R was applied to screen for differentially expressed microRNAs (DEmiRNAs) between the embolic stroke group and thrombotic stroke group. The miRWalk was utilized to predict the target genes of DEmiRNAs. Genes associated with embolic stroke were downloaded from the Comparative Toxicogenomics Database. Cross reference of target genes to disease related genes was conducted to construct the DEmiRNA-gene network. The protein-protein interaction (PPI) network of overlapping genes was evaluated by STRING, using the MCODE and CytoHubba plugin of Cytoscape to identify the modules and hub genes. The enrichment of Kyoto Encyclopedia of Genes and Genomes (KEGG) in modules was performed. There were 30 microRNAs in total identified as DEmiRNAs between embolic stroke and thrombotic stroke groups, of which 8 were upregulated and 22 were downregulated. Among these differentially expressed miRNAs, miR-15a-5p, miR-17-5p, miR-19b-3p, and miR-20a-5p were significantly associated with an ES to TS. Using the miRWalk 3.0 online tool, target genes regulated by DEmiRNAs were predicted. In addition, disease related genes were predicted and compared with target genes of DEmiRNAs. 166 overlapped genes regulated by miR-15a-5p, miR-17-5p, miR-19b-3p, and miR-20a-5p were identified, suggesting their association with diseases that contributed to ES, mainly including atrial fibrillation, mitral valve stenosis, myocardial infarction, and aortic dissection. Therefore, miR-15a-5p, miR-17-5p, miR-19b-3p, and miR-20a-5p were promising candidate biomarkers for differentiating an ES from TS. The PPI network demonstrated that miR-15a-5p, miR-17-5p, miR-19b-3p, and miR-20a-5p were associated with an ES by mainly regulating “CCND1, E2F2, E2F3, ITCH, UBE4A, UBE3C, RBL2, FBXO31, EIF2C4, and EIF2C1”. Furthermore, miR-15a-5p and miR-17-5p may function through “cell cycle, prostate cancer, and small cell lung cancer” while miR-19b-3p and miR-20a-5p function through “insulin resistance, hepatitis B, and viral carcinogenesis” and “vasopressin-regulated water reabsorption”, respectively. However, these results were approached in the manner of bioinformatics analysis; therefore, further verification is required.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 623.1-623
Author(s):  
C. Wang ◽  
S. X. Zhang ◽  
S. Song ◽  
J. Qiao ◽  
R. Zhao ◽  
...  

Background:Nephritis is one of the predominant causes of morbidity and mortality in patients with lupus1 2.The lack of understanding regarding the molecular mechanisms of lupus nephritis(LN) hinders the development of specific targeted therapy for this progressive disease3.Objectives:In this study, we use bioinformatics method to analyze the genes involved in regulating the potential pathogenesis of LN.Methods:The expression profile of LN(GSE104948 and GSE32591) was obtained from the GEO database.GSE104948 was a memory chip, which included 32 LN glomerular biopsy tissues and 3 glomerular tissues from living donors.GSE32591 dataset included 32 LN glomerular biopsy tissues and 15 glomerular tissues from living donors. The Oligo package was used to process the data to obtain the expression matrix files of all the related genes.P<0.05 and |log2(FC)|>2 were setted as cut-off criteria for the DEGs.Ggplot2, heatmap packages were used to DEGs visualization. Metascape online tool was used to annotating DEGs for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis performed.We used STRING online database to construct protein-protein interaction (PPI) network. Hub genes were identified by Cytoscape.Results:In differential expression analysis,357 DEGs were identified,including 248 up-regulated genes and 109 down-regulated genes (Figure 1A,B).GO enrichment showed that these DEGs were primarily enriched in biological pathways, cell localization and molecular function and revealed that LN-related genes mainly involved in immune response.KEGG pathway annotation enrichment analysis revealed these DEGs were closely associated with Staphylococcus aureus infection,Complement and coagulation cascades (Figure 1D). Fourteen hub genes(IFT3,IRF7,OAS3,GBP2,RSAD2,MX1,IFIT2,IFI6,MX2,ISF15,IFIT1,QAS2,OASL,OAS1) were identified from PPI network (Figure 1C,E).Conclusion:Illuminating the molecular mechanisms of LN was help for deep understanding of LN.References:[1]Song J, Zhao L, Li Y. Comprehensive bioinformatics analysis of mRNA expression profiles and identification of a miRNA-mRNA network associated with lupus nephritis. Lupus 2020;29(8):854-61. doi: 10.1177/0961203320925155 [published Online First: 2020/05/22].[2]Yao F, Sun L, Fang W, et al. HsamiR3715p inhibits human mesangial cell proliferation and promotes apoptosis in lupus nephritis by directly targeting hypoxiainducible factor 1alpha. Mol Med Rep 2016;14(6):5693-98. doi: 10.3892/mmr.2016.5939 [published Online First: 2016/11/24].[3]Dall’Era M. Treatment of lupus nephritis: current paradigms and emerging strategies. Curr Opin Rheumatol 2017;29(3):241-47. doi: 10.1097/BOR.0000000000000381 [published Online First: 2017/02/17].Acknowledgements:This project was supported by National Science Foundation of China (82001740), Open Fund from the Key Laboratory of Cellular Physiology (Shanxi Medical University) (KLCP2019) and Innovation Plan for Postgraduate Education in Shanxi Province (2020BY078).Disclosure of Interests:None declared


2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Yaowei Li ◽  
Li Li

Abstract Background Ovarian carcinoma (OC) is a common cause of death among women with gynecological cancer. MicroRNAs (miRNAs) are believed to have vital roles in tumorigenesis of OC. Although miRNAs are broadly recognized in OC, the role of has-miR-182-5p (miR-182) in OC is still not fully elucidated. Methods We evaluated the significance of miR-182 expression in OC by using analysis of a public dataset from the Gene Expression Omnibus (GEO) database and a literature review. Furthermore, we downloaded three mRNA datasets of OC and normal ovarian tissues (NOTs), GSE14407, GSE18520 and GSE36668, from GEO to identify differentially expressed genes (DEGs). Then the targeted genes of hsa-miR-182-5p (TG_miRNA-182-5p) were predicted using miRWALK3.0. Subsequently, we analyzed the gene overlaps integrated between DEGs in OC and predicted target genes of miR-182 by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. STRING and Cytoscape were used to construct a protein-protein interaction (PPI) network and the prognostic effects of the hub genes were analyzed. Results A common pattern of up-regulation for miR-182 in OC was found in our review of the literature. A total of 268 DEGs, both OC-related and miR-182-related, were identified, of which 133 genes were discovered from the PPI network. A number of DEGs were enriched in extracellular matrix organization, pathways in cancer, focal adhesion, and ECM-receptor interaction. Two hub genes, MCM3 and GINS2, were significantly associated with worse overall survival of patients with OC. Furthermore, we identified covert miR-182-related genes that might participate in OC by network analysis, such as DCN, AKT3, and TIMP2. The expressions of these genes were all down-regulated and negatively correlated with miR-182 in OC. Conclusions Our study suggests that miR-182 is essential for the biological progression of OC.


2020 ◽  
Vol 11 ◽  
Author(s):  
Weiming Gong ◽  
Ping Guo ◽  
Lu Liu ◽  
Qingbo Guan ◽  
Zhongshang Yuan

Idiopathic pulmonary fibrosis (IPF) is a type of scarring lung disease characterized by a chronic, progressive, and irreversible decline in lung function. The genetic basis of IPF remains elusive. A transcriptome-wide association study (TWAS) of IPF was performed by FUSION using gene expression weights of three tissues combined with a large-scale genome-wide association study (GWAS) dataset, totally involving 2,668 IPF cases and 8,591 controls. Significant genes identified by TWAS were then subjected to gene ontology (GO) and pathway enrichment analysis. The overlapped GO terms and pathways between enrichment analysis of TWAS significant genes and differentially expressed genes (DEGs) from the genome-wide mRNA expression profiling of IPF were also identified. For TWAS significant genes, protein–protein interaction (PPI) network and clustering modules analyses were further conducted using STRING and Cytoscape. Overall, TWAS identified a group of candidate genes for IPF under the Bonferroni corrected P value threshold (0.05/14929 = 3.35 × 10–6), such as DSP (PTWAS = 1.35 × 10–29 for lung tissue), MUC5B (PTWAS = 1.09 × 10–28 for lung tissue), and TOLLIP (PTWAS = 1.41 × 10–15 for whole blood). Pathway enrichment analysis identified multiple candidate pathways, such as herpes simplex infection (P value = 7.93 × 10–5) and antigen processing and presentation (P value = 6.55 × 10–5). 38 common GO terms and 8 KEGG pathways shared by enrichment analysis of TWAS significant genes and DEGs were identified. In the PPI network, 14 genes (DYNLL1, DYNC1LI1, DYNLL2, HLA-DRB5, HLA-DPB1, HLA-DQB2, HLA-DQA2, HLA-DQB1, HLA-DRB1, POLR2L, CENPP, CENPK, NUP133, and NUP107) were simultaneously detected by hub gene and module analysis. In conclusion, through integrative analysis of TWAS and mRNA expression profiles, we identified multiple novel candidate genes, GO terms and pathways for IPF, which contributes to the understanding of the genetic mechanism of IPF.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Suthanthiram Backiyarani ◽  
Rajendran Sasikala ◽  
Simeon Sharmiladevi ◽  
Subbaraya Uma

AbstractBanana, one of the most important staple fruit among global consumers is highly sterile owing to natural parthenocarpy. Identification of genetic factors responsible for parthenocarpy would facilitate the conventional breeders to improve the seeded accessions. We have constructed Protein–protein interaction (PPI) network through mining differentially expressed genes and the genes used for transgenic studies with respect to parthenocarpy. Based on the topological and pathway enrichment analysis of proteins in PPI network, 12 candidate genes were shortlisted. By further validating these candidate genes in seeded and seedless accession of Musa spp. we put forward MaAGL8, MaMADS16, MaGH3.8, MaMADS29, MaRGA1, MaEXPA1, MaGID1C, MaHK2 and MaBAM1 as possible target genes in the study of natural parthenocarpy. In contrary, expression profile of MaACLB-2 and MaZEP is anticipated to highlight the difference in artificially induced and natural parthenocarpy. By exploring the PPI of validated genes from the network, we postulated a putative pathway that bring insights into the significance of cytokinin mediated CLAVATA(CLV)–WUSHEL(WUS) signaling pathway in addition to gibberellin mediated auxin signaling in parthenocarpy. Our analysis is the first attempt to identify candidate genes and to hypothesize a putative mechanism that bridges the gaps in understanding natural parthenocarpy through PPI network.


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