MicroRNA-362-3p Inhibits Glioma Growth by Targeting PAX3 and Regulating Wnt/Beta-Catenin Pathway

Glioma is the most common intracranial malignancy and has been recognized as one of the most invasive primary tumors. Although there have been many studies on its growth mechanism, the molecular mechanism for growth inhibition is still unclear. The aim of this study was to show that microRNA-362-3p inhibits glioma growth by targeting PAX3 and regulating Wnt/beta-catenin pathway. We collected platelets from 12 healthy controls and 8 patients with glioma from the GEO database for comparison. The ncRNA and transcription factors that regulate the module were predicted to reveal the mechanism of microRNA-362-3p through co-expression module analysis, enrichment analysis, and hypergeometric testing. Two functional modules were obtained by integrating potential pathogenic genes and co-expression analysis. GPATCH4 and MYOD1 genes were expressed differentially and had active regulatory roles in the dysfunction module; thus, they were identified as key genes for glioma growth. Next, we performed ncRNA pivot and transcription factors (TFs) especially about the pivot analysis. The results showed microRNA-362-3p gene interest that significantly regulated the dysfunction module. Therefore, we identified microRNA-362-3p as a dysfunctional molecule in the growth process of glioma. MicroRNA-362-3p could inhibit glioma growth by targeting PAX3 and regulating the Wnt/beta-catenin pathway. The inhibition of this pathway may be a new target for the treatment of glioma. This study improves our understanding of growth inhibition in glioma and provides reference values for the treatment of this disease.

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Identification of pathogenic genes and transcription factors in respiratory syncytial virus

BMC Pediatrics ◽

10.1186/s12887-020-02480-4 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Lei Li ◽

Yong An Ni ◽

Zhenfeng Song ◽

Zhi Yi ◽

Fang Wang

Keyword(s):

Transcription Factors ◽

Respiratory Syncytial Virus ◽

Respiratory Infections ◽

Transcriptional Regulatory Network ◽

Enrichment Analysis ◽

Microarray Dataset ◽

Integrated Analysis ◽

Pathogenic Genes ◽

Transcriptional Regulatory ◽

Syncytial Virus

Abstract Background Respiratory syncytial virus (RSV) is a major cause of acute lower respiratory infections in children, especially bronchiolitis. Our study aimed to identify the key genes and upstream transcription factors in RSV. Methods To screen for RSV pathogenic genes, an integrated analysis was performed using the RSV microarray dataset in GEO. Functional annotation and potential pathways for differentially expressed genes (DEGs) were further explored by GO and KEGG enrichment analysis. We constructed the RSV-specific transcriptional regulatory network to identify key transcription factors for DEGs in RSV. Results From three GEO datasets, we identified 1059 DEGs (493 up-regulated and 566 down-regulated genes, FDR < 0.05 and |Combined.ES| > 0.8) between RSV patients and normal controls. GO and KEGG analysis revealed that ‘response to virus’ (FDR = 7.13E-15), ‘mitochondrion’ (FDR = 1.39E-14) and ‘Asthma’ (FDR = 1.28E-06) were significantly enriched pathways for DEGs. The expression of IFI27, IFI44, IFITM3, FCER1A, and ISG15 were shown to be involved in the pathogenesis of RSV. Conclusions We concluded that IFI27, IFI44, IFITM3, FCER1A, and ISG15 may play a role in RSV. Our finding may contribute to the development of new potential biomarkers, reveal the underlying pathogenesis and also identify novel therapeutic targets for RSV.

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Identification of Potential Therapeutic Targets For Rheumatoid Arthritis By Bioinformatics

10.21203/rs.3.rs-538306/v1 ◽

2021 ◽

Author(s):

Yi-kuan Du ◽

Erbai Ye ◽

Xiaoling Xiao ◽

Senpeng Zhang ◽

XinNi Ye ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Transcription Factors ◽

Signaling Pathway ◽

Programming Language ◽

Enrichment Analysis ◽

R Programming Language ◽

Key Genes ◽

R Programming ◽

Geo Database ◽

Differential Genes

Abstract Objective: Based on GEO database, we performed bioinformatics analysis on rheumatoid arthritis (RA)-related gene chips to obtain key genes and signaling pathways of RA, understand the molecular mechanism of RA occurrence and development, and provide candidate targets for the diagnosis and treatment of RA.Methods: The chip GSE77298 related to rheumatoid arthritis in GEO database was retrieved, and the R Programming Language analyzed the differential genes. Subsequently, the differential gene protein-protein interaction (PPI) relationship was constructed. The hub gene was screened, and the DAVID database was used for GO enrichment analysis and KEGG pathway analysis of key differential genes. The miRNAs were then subjected to target gene prediction, and then a miRNA-mRNA visualization network map was constructed using Cytoscape. Finally, transcription factors were predicted by the AnimalTFDB database.Results: ①The chip with the serial number of GSE77298 was retrieved from GEO database, and 1539 differential genes were screened out using the R Programming language analysis, including 1156 up-regulated genes and 383 down-regulated genes. ②By DAVID online functional enrichment analysis of differential genes, it was shown that the signaling pathways were mainly rheumatoid arthritis, Staphylococcus aureus infection, chemokine signaling pathway, viral myocarditis, cytokine-cytokine receptor interaction, etc. ③PPI was constructed through String database. Its hub genes were CXCL12, CD44 and CDH2. The top 10 key differential genes in Degree were CXCL8, PTPRC, MMP9, TLR2, FN1, ITGB2, CXCL1, CCL5, CXCR4 and CXCL10. ④Ten important miRNAs such as hsa-miR-30a-3p, hsa-miR-34a-5p, hsa-miR-30d-3p were predicted. ⑤Transcription factors such as GTF3C2, GLYR1, TRIM24, YY1 were predicted.Conclusion: PI3K-AKT signaling pathway and many other pathways are involved in the occurrence and development of RA, and CXCL8, SOCS3, and TLR2 genes may be the key genes in RA. Ten important miRNAs such as has-miR-340-5p may participate in the pathogenesis of RA. Many transcription factors such as YY1 may be involved in RA's disease process, which will provide directions for further research on RA diagnosis and treatment targets of RA.

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Anti-glioma Efficacy and Mechanism of Action of Tripolinolate A from Tripolium pannonicum

Planta Medica ◽

10.1055/s-0044-101038 ◽

2018 ◽

Vol 84 (11) ◽

pp. 786-794

Author(s):

Weiyun Chai ◽

Lu Chen ◽

Xiao-Yuan Lian ◽

Zhizhen Zhang

Keyword(s):

Cell Cycle ◽

Transcription Factors ◽

Glioma Cells ◽

Inhibitory Effect ◽

Cell Cycle Regulators ◽

Expression Levels ◽

Multiple Tumor ◽

Glioma Growth

AbstractTripolinolate A as a new bioactive phenolic ester was previously isolated from a halophyte of Tripolium pannonicum. However, the in vitro and in vivo anti-glioma effects and mechanism of tripolinolate A have not been investigated. This study has demonstrated that (1) tripolinolate A inhibited the proliferation of different glioma cells with IC50 values of 7.97 to 14.02 µM and had a significant inhibitory effect on the glioma growth in U87MG xenograft nude mice, (2) tripolinolate A induced apoptosis in glioma cells by downregulating the expressions of antiapoptotic proteins and arrested glioma cell cycle at the G2/M phase by reducing the expression levels of cell cycle regulators, and (3) tripolinolate A also remarkably reduced the expression levels of several glioma metabolic enzymes and transcription factors. All data together suggested that tripolinolate A had significant in vitro and in vivo anti-glioma effects and the regulation of multiple tumor-related regulators and transcription factors might be responsible for the activities of tripolinolate A against glioma.

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Identification of Key Genes and Pathways Associated with Differences of Subchondral Bone in Osteoarthritis

10.21203/rs.3.rs-51799/v1 ◽

2020 ◽

Author(s):

Yiyuan Zhang ◽

Rongguo Yu ◽

Jiayu Zhang ◽

Eryou Feng ◽

Haiyang Wang ◽

...

Keyword(s):

Subchondral Bone ◽

Molecular Mechanisms ◽

Enrichment Analysis ◽

Functional Enrichment Analysis ◽

Functional Enrichment ◽

Hub Genes ◽

Common Chronic Disease ◽

Drug Candidates ◽

Therapeutic Modalities ◽

Pathogenic Genes

Abstract BackgroundOsteoarthritis (OA) is a common chronic disease worldwide. Subchondral bone is an important pathological change in OA and responds more rapidly to adverse loading and events compared to cartilage. However, the pathogenic genes and pathways of subchondral bone are largely unclear.ObjectiveThis study aimed to identify signature differences in genes involved in knee lateral tibial (LT) and medial tibial (MT) plateaus of subchondral bone tissue while exploring their potential molecular mechanisms via bioinformatics analysis.MethodsFirst, the gene expression data of GSE51588 was downloaded from the GEO database. Differentially expressed genes (DEGs) between knee LT and MT were identified, and functional enrichment analyses were performed. Then, a protein-protein interactive network was constructed in order to acquire the hub genes, and modules analysis was conducted using STRING and Cytoscape for further analysis. The enriched hub genes were queried in DGIdb database to find suitable drug candidates in OA.ResultsA total of 202 DEGs (112 upregulated genes and 84 downregulated genes) were determined. In the PPI network, ten hub genes were identified. Five significant modules were identified using the MCODE plugin unit. Functional enrichment analysis revealed the most important signaling pathways. Six of the ten hub genes were targetable by a total of 35 drugs, suggesting their possible therapeutic use for OA .ConclusionsThe identified hub genes and functional enrichment pathways were implicated in the development and progression of subchondral bone in OA, thus improving our understanding of OA and offering molecular targets for future therapeutic modalities.

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Transcriptomic profiles of non-embryogenic and embryogenic callus cells in a highly regenerative Upland Cotton line (Gossypium hirsutum L.)

10.21203/rs.3.rs-28441/v1 ◽

2020 ◽

Author(s):

Li Wen ◽

Wei Li ◽

Stephen Parris ◽

Matthew West ◽

John Lawson ◽

...

Keyword(s):

Gene Expression ◽

Somatic Embryogenesis ◽

Transcription Factors ◽

Gossypium Hirsutum ◽

Embryogenic Callus ◽

Developmental Stages ◽

Baby Boom ◽

Expression Profiles ◽

Enrichment Analysis ◽

Study Gene Expression

Abstract • Background • Genotype independent transformation and whole plant regeneration through somatic embryogenesis relies heavily on the intrinsic ability of a genotype to regenerate. • Results • In this study, gene expression profiles of a highly regenerable Gossypium hirsutum L. cultivar, Jin668, were analyzed at two critical developmental stages during somatic embryogenesis, non-embryogenic callus (NEC) cells and embryogenic callus (EC) cells. The rate of EC formation in Jin668 is 96%. Differential gene expression analysis revealed a total of 5,333 differentially expressed genes (DEG) with 2,534 upregulated and 2,799 downregulated in EC. A total of 144 genes were unique to NEC cells and 174 genes unique to EC. Clustering and enrichment analysis identified genes upregulated in EC that function as transcription factors/DNA binding, phytohormone response, oxidative reduction, and regulators of transcription; while genes categorized in methylation pathways were downregulated. Four key transcription factors were identified based on their sharp upregulation in EC tissue; LEAFY COTYLEDON 1 (LEC1), BABY BOOM (BBM), FUSCA (FUS3) and AGAMOUS-LIKE15 with distinguishable subgenome expression bias. • Conclusions • This comparative analysis of NEC and EC transcriptomes gives new insights into the genetic underpinnings of somatic embryogenesis in cotton.

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Sperm cryopreservation impacts the early development of equine embryos by downregulating specific transcription factors

10.1101/2021.05.12.443855 ◽

2021 ◽

Author(s):

Jose Manuel Ortiz-Rodriguez ◽

Francisco Eduardo Martin-Cano ◽

Gemma L Gaitskell-Phillips ◽

Alberto Alvarez Barrientos ◽

Heriberto Rodriguez-Martínez ◽

...

Keyword(s):

Transcription Factors ◽

Enrichment Analysis ◽

Sperm Cryopreservation ◽

Pseudouridine Synthase ◽

Maturation Factor ◽

Human Orthologs ◽

Specific Factors ◽

Lipase Maturation Factor 1 ◽

Next Generation Sequencing Ngs ◽

Generation Sequencing

Equine embryos were obtained by insemination with either fresh or frozen-thawed spermatozoa at 8, 10 and 12 h post spontaneous ovulation, maintaining the pairs mare-stallion for the type of semen used. Next generation sequencing (NGS) was performed in all embryos and bioinformatic and enrichment analysis performed on the 21,058 identified transcripts. A total of 165 transcripts were downregulated in embryos obtained with cryopreserved spermatozoa respect embryos resulting from an insemination with fresh spermatozoa (p=0.021, q=0.1). The enrichment analysis using human orthologs using g:profiler on the downregulated transcripts marked an enrichment in transcription factors (TFs) in mRNAs downregulated in embryos obtained after insemination with cryopreserved spermatozoa. The 12 mRNAs (discriminant variables) most significantly downregulated in these embryos included among others, the chromatin-remodeling ATPase INO80, Lipase maturation factor 1 LMF1, the mitochondrial mRNA pseudouridine synthase RPUSD3, LIM and cysteine-rich domains protein 1, LMCD1. Sperm cryopreservation also caused a significant impact on the embryos at 8 to 10 days of development, but especially in the transition from 10 to 12 days. Overall, our findings provide strong evidence that insemination with cryopreserved spermatozoa poses a major impact in embryo development that may compromise its growth and viability, probably due to modifications in sperm proteins induced by cryopreservation. Identification of specific factors in the spermatozoa causing these changes may improve cryopreservation.

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MicroRNA-based regulation of genomics and transcriptomics of inflammatory cytokines in COVID-19

10.1101/2021.06.08.21258565 ◽

2021 ◽

Author(s):

Manoj Khokhar ◽

Sojit Tomo ◽

Purvi Purohit

Keyword(s):

Transcription Factors ◽

Inflammatory Response ◽

In Silico ◽

Wide Spectrum ◽

Interaction Network ◽

In Silico Analysis ◽

Enrichment Analysis ◽

Microarray Dataset ◽

Therapeutic Strategies ◽

Protein Protein Interaction

Background: Coronavirus disease 2019 is characterized by the elevation of a wide spectrum of inflammatory mediators which are associated with poor disease outcomes. We aimed at an in-silico analysis of regulatory microRNA and their transcription factors (TF) for these inflammatory genes that may help to devise potential therapeutic strategies in the future. Methods: The cytokine regulating immune-expressed genes (CRIEG) were sorted from literature and GEO microarray dataset and their co-differentially expressed miRNA and transcription factors were predicted from publicly available databases. Enrichment analysis was done through mienturnet, MiEAA, and Gene Ontology, and pathways predicted by KEGG and Reactome pathways. The functional and regulatory features were analyzed and visualized through Cytoscape. Results: Sixteen CRIEG were observed to have a significant protein-protein interaction network. The ontological analysis revealed significantly enriched pathways for biological processes, molecular functions, and cellular components. The search performed in the miRNA database yielded 10 miRNAs that are significantly involved in the regulation of these genes and their transcription factors. Conclusion: An In-Silico representation of a network involving miRNAs, CRIEGs, and TF which take part in the inflammatory response in COVID-19 has been elucidated. These regulatory factors may have potentially critical roles in the inflammatory response in COVID-19 and may be explored further for the development of targeted therapeutic strategies and mechanistic validation.

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Glioma growth inhibition by neurostatin and O-But GD1b

Neuro-Oncology ◽

10.1093/neuonc/noq073 ◽

2010 ◽

Vol 12 (11) ◽

pp. 1135-1146 ◽

Cited By ~ 6

Author(s):

B. Valle-Argos ◽

D. Gomez-Nicola ◽

M. Nieto-Sampedro

Keyword(s):

Growth Inhibition ◽

Glioma Growth

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

International Journal of Molecular Sciences ◽

10.3390/ijms21031053 ◽

2020 ◽

Vol 21 (3) ◽

pp. 1053 ◽

Cited By ~ 4

Author(s):

Alejandro Cabrera-Andrade ◽

Andrés López-Cortés ◽

Gabriela Jaramillo-Koupermann ◽

César Paz-y-Miño ◽

Yunierkis Pérez-Castillo ◽

...

Keyword(s):

Molecular Mechanisms ◽

Bone Cancer ◽

Interaction Network ◽

Enrichment Analysis ◽

Protein Protein Interaction ◽

Pathogenic Genes ◽

Total List ◽

Consensus Strategy ◽

Primary Bone ◽

Molecular Etiology

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

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CUL1-Mediated Organelle Fission Pathway Inhibits the Development of Chronic Obstructive Pulmonary Disease

Computational and Mathematical Methods in Medicine ◽

10.1155/2020/5390107 ◽

2020 ◽

Vol 2020 ◽

pp. 1-11

Author(s):

Ran Li ◽

Feng Xu ◽

Xiao Wu ◽

Shaoping Ji ◽

Ruixue Xia

Keyword(s):

Chronic Obstructive Pulmonary Disease ◽

Transcription Factors ◽

Pulmonary Disease ◽

Target Genes ◽

Enrichment Analysis ◽

Development Trend ◽

Chronic Obstructive ◽

Hypergeometric Test ◽

Obstructive Pulmonary Disease ◽

Depth Analysis

Chronic obstructive pulmonary disease (COPD) is a global high-incidence chronic airway inflammation disease. Its deterioration will lead to more serious lung lesions and even lung cancer. Therefore, it is urgent to determine the pathogenesis of COPD and find potential therapeutic targets. The purpose of this study is to reveal the molecular mechanism of COPD disease development through in-depth analysis of transcription factors and ncRNA-driven pathogenic modules of COPD. We obtained the expression profile of COPD-related microRNAs from the NCBI-GEO database and analyzed the differences among groups to identify the microRNAs significantly associated with COPD. Then, their target genes are predicted and mapped to a protein-protein interaction (PPI) network. Finally, key transcription factors and the ncRNA of the regulatory module were identified based on the hypergeometric test. The results showed that CUL1 was the most interactive gene in the highly interactive module, so it was recognized as a dysfunctional molecule of COPD. Enrichment analysis also showed that it was much involved in the biological process of organelle fission, the highest number of regulatory modules. In addition, ncRNAs, mainly composed of miR-590-3p, miR-495-3p, miR-186-5p, and transcription factors such as MYC, BRCA1, and CDX2, significantly regulate COPD dysfunction blocks. In summary, we revealed that the COPD-related target gene CUL1 plays a key role in the potential dysfunction of the disease. It promotes the proliferation of fibroblast cells in COPD patients by mediating functional signals of organelle fission and thus participates in the progress of the disease. Our research helps biologists to further understand the etiology and development trend of COPD.

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