scholarly journals Identification of a Transcription Factor-microRNA-Gene Coregulation Network in Meningioma through a Bioinformatic Analysis

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Juan Wang ◽  
Yan Liang ◽  
Hui Yang ◽  
Jian-Huang Wu

Background. Meningioma is a prevalent type of brain tumor. However, the initiation and progression mechanisms involved in the meningioma are mostly unknown. This study aimed at exploring the potential transcription factors/micro(mi)RNAs/genes and biological pathways associated with meningioma. Methods. mRNA expressions from GSE88720, GSE43290, and GSE54934 datasets, containing data from 83 meningioma samples and eight control samples, along with miRNA expression dataset GSE88721, which had 14 meningioma samples and one control sample, were integrated analyzed. The bioinformatics approaches were used for identifying differentially expressed genes and miRNAs, as well as predicting transcription factor targets related to the differentially expressed genes. The approaches were also used for gene ontology term analysis and biological pathway enrichment analysis, construction, and analysis of protein-protein interaction network, and transcription factor-miRNA-gene coregulation network construction. Results. Fifty-six upregulated and 179 downregulated genes were identified. Thirty transcription factors able to target the differentially expressed genes were predicted and selected based on public databases. One hundred seventeen overlapping genes were identified from the differentially expressed genes and the miRNAs predicted by miRWalk. Furthermore, NF-κB/IL6, PTGS2, MYC/hsa-miR-574-5p, hsa-miR-26b-5p, hsa-miR-335-5p, and hsa-miR-98-5p, which are involved in the transcription factor-miRNA-mRNA coregulation network, were found to be associated with meningioma. Conclusion. The bioinformatics analysis identified several potential molecules and relevant pathways that may represent critical mechanisms involved in the progression and development of meningioma. This work provides new insights into meningioma pathogenesis and treatments.

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e9119
Author(s):  
Priyansh Srivastava ◽  
Alakto Choudhury ◽  
Mehak Talwar ◽  
Sabyasachi Mohanty ◽  
Priyanka Narad ◽  
...  

Vitiligo is a chronic asymptomatic disorder affecting melanocytes from the basal layer of the epidermis which leads to a patchy loss of skin color. Even though it is one of the neglected disease conditions, people suffering from vitiligo are more prone to psychological disorders. As of now, various studies have been done in order to project auto-immune implications as the root cause. To understand the complexity of vitiligo, we propose the Vitiligo Information Resource (VIRdb) that integrates both the drug-target and systems approach to produce a comprehensive repository entirely devoted to vitiligo, along with curated information at both protein level and gene level along with potential therapeutics leads. These 25,041 natural compounds are curated from Natural Product Activity and Species Source Database. VIRdb is an attempt to accelerate the drug discovery process and laboratory trials for vitiligo through the computationally derived potential drugs. It is an exhaustive resource consisting of 129 differentially expressed genes, which are validated through gene ontology and pathway enrichment analysis. We also report 22 genes through enrichment analysis which are involved in the regulation of epithelial cell differentiation. At the protein level, 40 curated protein target molecules along with their natural hits that are derived through virtual screening. We also demonstrate the utility of the VIRdb by exploring the Protein–Protein Interaction Network and Gene–Gene Interaction Network of the target proteins and differentially expressed genes. For maintaining the quality and standard of the data in the VIRdb, the gold standard in bioinformatics toolkits like Cytoscape, Schrödinger’s GLIDE, along with the server installation of MATLAB, are used for generating results. VIRdb can be accessed through “http://www.vitiligoinfores.com/”.


2018 ◽  
Author(s):  
Jie Chen ◽  
Chaofeng Xing ◽  
Haosen Wang ◽  
Zengmeng Zhang ◽  
Daolun Yu ◽  
...  

AbstractTranscription factor ZBTB38 belongs to the zinc finger protein family and contains the typical BTB domains. Only several predicted BTB domain-containing proteins encoded in the human genome have been functionally characterized. No relevant studies have been reported concerning the effect of down-regulated ZBTB38 gene expression on tumor cells through transcriptome analysis. In the present study, 2,438 differentially expressed genes in ZBTB38−/− SH-SY5Y cells were obtained via high-throughput transcriptome sequencing analysis, 83.5% of which was down-regulated. Furthermore, GO functional clustering and KEGG pathway enrichment analysis of these differentially expressed genes (DEGs) revealed that the knocked-down transcription factor ZBTB38 interacted with p53 and arrested cell cycles to inhibit the proliferation of the tumor cells. Besides, it also significantly down-regulated the expressions of PTEN, a “molecular switch” of the PI3K/Akt signaling pathway, and RB1CC1, the key gene for autophagy initiation, and blocked autophagy to accelerate the apoptosis of tumor cells. ZBTB38−/− SH-SY5Y cells were investigated at the whole transcriptome level and key DEGs were screened in the present study for the first time, providing a theoretical foundation for exploring the molecular mechanism of inhibition of tumor cell proliferation and targeted anti-tumor therapies.


2021 ◽  
pp. 1169-1180
Author(s):  
Seyedeh Faezeh Hassani ◽  
Masoud Sayaf ◽  
Seyedeh Sara Danandeh ◽  
Zahra Nourollahzadeh ◽  
Mahshid Shahmohammadi ◽  
...  

PURPOSE This study aims to identify potential biomarkers of hepatocellular carcinoma (HCC) occurrence/recurrence and obesity, along with the molecular mechanisms that involve these biomarkers. METHODS Three microarray data sets, namely GSE18897, GSE25097, and GSE36376 (genetic suppressor elements associated with obesity, tumor, and recurrence, respectively), were downloaded from Gene Expression Omnibus database to be investigated for their expression as differentially expressed genes (DEGs) in HCC and obesity. The functional and pathway enrichment analysis of these DEGs were identified by the Database for Annotation Visualization and Integrated Discovery. The protein-protein interaction network analysis was performed with STRING online tool and Cytoscape software. RESULTS One hundred sixty common DEGs were screened. We found that these genes were associated with certain pathways such as metabolic pathways, terpenoid backbone biosynthesis, and adipocytokine signaling pathway. The involvements of 10 genes, including RPS16, RPS7, CCT3, HNRNPA2B1, EIF4G1, PSMC4, NHP2, EGR1, FDPS, and MCM4, were identified in the subnetwork. HNRNPA2B1 and RPS7 in the GSE18897 data set, RPS16, RPS7, CCT3, HNRNPA2B1, PSMC4, NHP2, FDPS, and MCM4 in the GSE25097 data set, and RPS16, RPS7, CCT3, HNRNPA2B1, EIF4G1, PSMC4, NHP2, FDPS, and MCM4 in the GSE36376 data set exhibited positive fold changes. CONCLUSION These DEGs and pathways could be of diagnostic value as potential biomarkers involved in the pathogenesis of HCC, pertaining to both obesity and HCC occurrence/recurrence.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Xin Yuan ◽  
Shenqiang Hu ◽  
Liang Li ◽  
Chunchun Han ◽  
Hehe Liu ◽  
...  

Abstract Background Despite their important functions and nearly ubiquitous presence in cells, an understanding of the biology of intracellular lipid droplets (LDs) in goose follicle development remains limited. An integrated study of lipidomic and transcriptomic analyses was performed in a cellular model of stearoyl-CoA desaturase (SCD) function, to determine the effects of intracellular LDs on follicle development in geese. Results Numerous internalized LDs, which were generally spherical in shape, were dispersed throughout the cytoplasm of granulosa cells (GCs), as determined using confocal microscopy analysis, with altered SCD expression affecting LD content. GC lipidomic profiling showed that the majority of the differentially abundant lipid classes were glycerophospholipids, including PA, PC, PE, PG, PI, and PS, and glycerolipids, including DG and TG, which enriched glycerophospholipid, sphingolipid, and glycerolipid metabolisms. Furthermore, transcriptomics identified differentially expressed genes (DEGs), some of which were assigned to lipid-related Gene Ontology slim terms. More DEGs were assigned in the SCD-knockdown group than in the SCD-overexpression group. Integration of the significant differentially expressed genes and lipids based on pathway enrichment analysis identified potentially targetable pathways related to glycerolipid/glycerophospholipid metabolism. Conclusions This study demonstrated the importance of lipids in understanding follicle development, thus providing a potential foundation to decipher the underlying mechanisms of lipid-mediated follicle development.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1037.2-1038
Author(s):  
X. Sun ◽  
S. X. Zhang ◽  
S. Song ◽  
T. Kong ◽  
C. Zheng ◽  
...  

Background:Psoriasis is an immune-mediated, genetic disease manifesting in the skin or joints or both, and also has a strong genetic predisposition and autoimmune pathogenic traits1. The hallmark of psoriasis is sustained inflammation that leads to uncontrolled keratinocyte proliferation and dysfunctional differentiation. And it’s also a chronic relapsing disease, which often necessitates a long-term therapy2.Objectives:To investigate the molecular mechanisms of psoriasis and find the potential gene targets for diagnosis and treating psoriasis.Methods:Total 334 gene expression data of patients with psoriasis research (GSE13355 GSE14905 and GSE30999) were obtained from the Gene Expression Omnibus database. After data preprocessing and screening of differentially expressed genes (DEGs) by R software. Online toll Metascape3 was used to analyze Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of DEGs. Interactions of proteins encoded by DEGs were discovered by Protein-protein interaction network (PPI) using STRING online software. Cytoscape software was utilized to visualize PPI and the degree of each DEGs was obtained by analyzing the topological structure of the PPI network.Results:A total of 611 DEGs were found to be differentially expressed in psoriasis. GO analysis revealed that up-regulated DEGs were mostly associated with defense and response to external stimulus while down-regulated DEGs were mostly associated with metabolism and synthesis of lipids. KEGG enrichment analysis suggested they were mainly enriched in IL-17 signaling, Toll-like receptor signaling and PPAR signaling pathways, Cytokine-cytokine receptor interaction and lipid metabolism. In addition, top 9 key genes (CXCL10, OASL, IFIT1, IFIT3, RSAD2, MX1, OAS1, IFI44 and OAS2) were identified through Cytoscape.Conclusion:DEGs of psoriasis may play an essential role in disease development and may be potential pathogeneses of psoriasis.References:[1]Boehncke WH, Schon MP. Psoriasis. Lancet 2015;386(9997):983-94. doi: 10.1016/S0140-6736(14)61909-7 [published Online First: 2015/05/31].[2]Zhang YJ, Sun YZ, Gao XH, et al. Integrated bioinformatic analysis of differentially expressed genes and signaling pathways in plaque psoriasis. Mol Med Rep 2019;20(1):225-35. doi: 10.3892/mmr.2019.10241 [published Online First: 2019/05/23].[3]Zhou Y, Zhou B, Pache L, et al. Metascape provides a biologist-oriented resource for the analysis of systems-level datasets. Nat Commun 2019;10(1):1523. doi: 10.1038/s41467-019-09234-6 [published Online First: 2019/04/05].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


2021 ◽  
Author(s):  
Li Guoquan ◽  
Du Junwei ◽  
He Qi ◽  
Fu Xinghao ◽  
Ji Feihong ◽  
...  

Abstract BackgroundHashimoto's thyroiditis (HT), also known as chronic lymphocytic thyroiditis, is a common autoimmune disease, which mainly occurs in women. The early manifestation was hyperthyroidism, however, hypothyroidism may occur if HT was not controlled for a long time. Numerous studies have shown that multiple factors, including genetic, environmental, and autoimmune factors, were involved in the pathogenesis of the disease, but the exact mechanisms were not yet clear. The aim of this study was to identify differentially expressed genes (DEGs) by comprehensive analysis and to provide specific insights into HT. MethodsTwo gene expression profiles (GSE6339, GSE138198) about HT were downloaded from the Gene Expression Omnibus (GEO) database. The DEGs were assessed between the HT and normal groups using the GEO2R. The DEGs were then sent to the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. The hub genes were discovered using Cytoscape and CytoHubba. Finally, NetworkAnalyst was utilized to create the hub genes' targeted microRNAs (miRNAs). ResultsA total of 62 DEGs were discovered, including 60 up-regulated and 2 down-regulated DEGs. The signaling pathways were mainly engaged in cytokine interaction and cytotoxicity, and the DEGs were mostly enriched in immunological and inflammatory responses. IL2RA, CXCL9, IL10RA, CCL3, CCL4, CCL2, STAT1, CD4, CSF1R, and ITGAX were chosen as hub genes based on the results of the protein-protein interaction (PPI) network and CytoHubba. Five miRNAs, including mir-24-3p, mir-223-3p, mir-155-5p, mir-34a-5p, mir-26b-5p, and mir-6499-3p, were suggested as likely important miRNAs in HT. ConclusionsThese hub genes, pathways and miRNAs contribute to a better understanding of the pathophysiology of HT and offer potential treatment options for HT.


2020 ◽  
Vol 2020 ◽  
pp. 1-18
Author(s):  
Xinhong Liu ◽  
Feng Chen ◽  
Fang Tan ◽  
Fang Li ◽  
Ruokun Yi ◽  
...  

Background. Breast cancer is a malignant tumor that occurs in the epithelial tissue of the breast gland and has become the most common malignancy in women. The regulation of the expression of related genes by microRNA (miRNA) plays an important role in breast cancer. We constructed a comprehensive breast cancer-miRNA-gene interaction map. Methods. Three miRNA microarray datasets (GSE26659, GSE45666, and GSE58210) were obtained from the GEO database. Then, the R software “LIMMA” package was used to identify differential expression analysis. Potential transcription factors and target genes of screened differentially expressed miRNAs (DE-miRNAs) were predicted. The BRCA GE-mRNA datasets (GSE109169 and GSE139038) were downloaded from the GEO database for identifying differentially expressed genes (DE-genes). Next, GO annotation and KEGG pathway enrichment analysis were conducted. A PPI network was then established, and hub genes were identified via Cytoscape software. The expression and prognostic roles of hub genes were further evaluated. Results. We found 6 upregulated differentially expressed- (DE-) miRNAs and 18 downregulated DE-miRNAs by analyzing 3 Gene Expression Omnibus databases, and we predicted the upstream transcription factors and downstream target genes for these DE-miRNAs. Then, we used the GEO database to perform differential analysis on breast cancer mRNA and obtained differentially expressed mRNA. We found 10 hub genes of upregulated DE-miRNAs and 10 hub genes of downregulated DE-miRNAs through interaction analysis. Conclusions. In this study, we have performed an integrated bioinformatics analysis to construct a more comprehensive BRCA-miRNA-gene network and provide new targets and research directions for the treatment and prognosis of BRCA.


2020 ◽  
Vol 9 (2) ◽  
pp. LMT30
Author(s):  
Chuanli Ren ◽  
Weixiu Sun ◽  
Xu Lian ◽  
Chongxu Han

Aim: To screen and identify key genes related to the development of smoking-induced lung adenocarcinoma (LUAD). Materials & methods: We obtained data from the GEO chip dataset GSE31210. The differentially expressed genes were screened by GEO2R. The protein interaction network of differentially expressed genes was constructed by STRING and Cytoscape. Finally, core genes were screened. The overall survival time of patients with the core genes was analyzed by Kaplan–Meier method. Gene ontology and Kyoto encyclopedia of genes and genomes bioaccumulation was calculated by DAVID. Results: Functional enrichment analysis indicated that nine key genes were actively involved in the biological process of smoking-related LUAD. Conclusion: 23 core genes and nine key genes among them were correlated with adverse prognosis of LUAD induced by smoking.


2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Wenqing Nai ◽  
Diane Threapleton ◽  
Jingbo Lu ◽  
Kewei Zhang ◽  
Hongyuan Wu ◽  
...  

Abstract Atherosclerosis is the primary cause of cardiovascular events and its molecular mechanism urgently needs to be clarified. In our study, atheromatous plaques (ATH) and macroscopically intact tissue (MIT) sampled from 32 patients were compared and an integrated series of bioinformatic microarray analyses were used to identify altered genes and pathways. Our work showed 816 genes were differentially expressed between ATH and MIT, including 443 that were up-regulated and 373 that were down-regulated in ATH tissues. GO functional-enrichment analysis for differentially expressed genes (DEGs) indicated that genes related to the “immune response” and “muscle contraction” were altered in ATHs. KEGG pathway-enrichment analysis showed that up-regulated DEGs were significantly enriched in the “FcεRI-mediated signaling pathway”, while down-regulated genes were significantly enriched in the “transforming growth factor-β signaling pathway”. Protein-protein interaction network and module analysis demonstrated that VAV1, SYK, LYN and PTPN6 may play critical roles in the network. Additionally, similar observations were seen in a validation study where SYK, LYN and PTPN6 were markedly elevated in ATH. All in all, identification of these genes and pathways not only provides new insights into the pathogenesis of atherosclerosis, but may also aid in the development of prognostic and therapeutic biomarkers for advanced atheroma.


2021 ◽  
Vol 23 (1) ◽  
pp. 382
Author(s):  
Tingting Zhu ◽  
Han Liu ◽  
Li Su ◽  
Ali Dawood ◽  
Changmin Hu ◽  
...  

Although Mycobacterium tuberculosis (MTB) has existed for thousands of years, its immune escape mechanism remains obscure. Increasing evidence signifies that microRNAs (miRNAs) play pivotal roles in the progression of tuberculosis (TB). RNA sequencing was used to sequence miRNAs in human acute monocytic leukemia cells (THP-1) infected by the virulent MTB-1458 strain and the avirulent vaccine strain Mycobacterium bovis Bacillus Calmette-Guérin (BCG). Sets of differentially expressed miRNAs (DE-miRNAs) between MTB-1458/BCG-infected groups and uninfected groups were identified, among which 18 were differentially expressed only in the MTB-1458-infected THP-1 group. Then, 13 transcription factors (TFs) and 81 target genes of these 18 DE-miRNAs were matched. Gene Ontology classification as well as Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed that the candidate targets were predominantly involved in apoptotic-associated and interferon-γ-mediated signaling pathways. A TF-miRNA-mRNA interaction network was constructed to analyze the relationships among these 18 DE-miRNAs and their targets and TFs, as well as display the hub miRNAs, TFs, and target genes. Considering the degrees from network analysis and the reported functions, this study focused on the BHLHE40-miR-378d-BHLHE40 regulation axis and confirmed that BHLHE40 was a target of miR-378d. This cross-talk among DE-miRNAs, mRNAs, and TFs might be an important feature in TB, and the findings merited further study and provided new insights into immune defense and evasion underlying host-pathogen interactions.


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