scholarly journals Lifespan-Associated Gene Expression Signatures of Recombinant BXD Mice Implicates Coro7 and Set in Longevity

2021 ◽  
Vol 12 ◽  
Author(s):  
David Vitiello ◽  
Alexander Dakhovnik ◽  
Cyril Statzer ◽  
Collin Y. Ewald

Although genetic approaches have identified key genes and pathways that promote longevity, systems-level approaches are less utilized. Here, we took advantage of the wealth of omics data characterizing the BXD family of mice. We associated transcript and peptide levels across five tissues from both female and male BXD isogenic lines with their median lifespan. We identified over 5000 genes that showed a longevity correlation in a given tissue. Surprisingly, we found less than 1% overlap among longevity-correlating genes across tissues and sex. These 1% shared genes consist of 51 genes, of which 13 have been shown to alter lifespan. Only two genes -Coro7 and Set- showed a longevity correlation in all tissues and in both sexes. While differential regulation of aging across tissues and sex has been reported, our systems-level analysis reveals two unique genes that may promote healthy aging in unique sex- and tissue-agnostic manner.

Author(s):  
Xitong Yang ◽  
Pengyu Wang ◽  
Shanquan Yan ◽  
Guangming Wang

AbstractStroke is a sudden cerebrovascular circulatory disorder with high morbidity, disability, mortality, and recurrence rate, but its pathogenesis and key genes are still unclear. In this study, bioinformatics was used to deeply analyze the pathogenesis of stroke and related key genes, so as to study the potential pathogenesis of stroke and provide guidance for clinical treatment. Gene Expression profiles of GSE58294 and GSE16561 were obtained from Gene Expression Omnibus (GEO), the differentially expressed genes (DEGs) were identified between IS and normal control group. The different expression genes (DEGs) between IS and normal control group were screened with the GEO2R online tool. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the DEGs were performed. Using the Database for Annotation, Visualization and Integrated Discovery (DAVID) and gene set enrichment analysis (GSEA), the function and pathway enrichment analysis of DEGS were performed. Then, a protein–protein interaction (PPI) network was constructed via the Search Tool for the Retrieval of Interacting Genes (STRING) database. Cytoscape with CytoHubba were used to identify the hub genes. Finally, NetworkAnalyst was used to construct the targeted microRNAs (miRNAs) of the hub genes. A total of 85 DEGs were screened out in this study, including 65 upward genes and 20 downward genes. In addition, 3 KEGG pathways, cytokine − cytokine receptor interaction, hematopoietic cell lineage, B cell receptor signaling pathway, were significantly enriched using a database for labeling, visualization, and synthetic discovery. In combination with the results of the PPI network and CytoHubba, 10 hub genes including CEACAM8, CD19, MMP9, ARG1, CKAP4, CCR7, MGAM, CD79A, CD79B, and CLEC4D were selected. Combined with DEG-miRNAs visualization, 5 miRNAs, including hsa-mir-146a-5p, hsa-mir-7-5p, hsa-mir-335-5p, and hsa-mir-27a- 3p, were predicted as possibly the key miRNAs. Our findings will contribute to identification of potential biomarkers and novel strategies for the treatment of ischemic stroke, and provide a new strategy for clinical therapy.


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 ◽  
Vol 104 (1) ◽  
pp. 003685042199727
Author(s):  
Xinyu Wang ◽  
Jiaojiao Yang ◽  
Xueren Gao

Lung adenocarcinoma (LUAD) is the most common histological type of lung cancer, comprising around 40% of all lung cancer. Until now, the pathogenesis of LUAD has not been fully elucidated. In the current study, we comprehensively analyzed the dysregulated genes in lung adenocarcinoma by mining public datasets. Two sets of gene expression datasets were obtained from the Gene Expression Omnibus (GEO) database. The dysregulated genes were identified by using the GEO2R online tool, and analyzed by R packages, Cytoscape software, STRING, and GPEIA online tools. A total of 275 common dysregulated genes were identified in two independent datasets, including 54 common up-regulated and 221 common down-regulated genes in LUAD. Gene Ontology (GO) enrichment analysis showed that these dysregulated genes were significantly enriched in 258 biological processes (BPs), 27 cellular components (CCs), and 21 molecular functions (MFs). Furthermore, protein-protein interaction (PPI) network analysis showed that PECAM1, ENG, KLF4, CDH5, and VWF were key genes. Survival analysis indicated that the low expression of ENG was associated with poor overall survival (OS) of LUAD patients. The low expression of PECAM1 was associated with poor OS and recurrence-free survival of LUAD patients. The cox regression model developed based on age, tumor stage, ENG, PECAM1 could effectively predict 5-year survival of LUAD patients. This study revealed some key genes, BPs, CCs, and MFs involved in LUAD, which would provide new insights into understanding the pathogenesis of LUAD. In addition, ENG and PECAM1 might serve as promising prognostic markers in LUAD.


2021 ◽  
Vol 20 ◽  
pp. 153303382098329
Author(s):  
Yujie Weng ◽  
Wei Liang ◽  
Yucheng Ji ◽  
Zhongxian Li ◽  
Rong Jia ◽  
...  

Human epidermal growth factor 2 (HER2)+ breast cancer is considered the most dangerous type of breast cancers. Herein, we used bioinformatics methods to identify potential key genes in HER2+ breast cancer to enable its diagnosis, treatment, and prognosis prediction. Datasets of HER2+ breast cancer and normal tissue samples retrieved from Gene Expression Omnibus and The Cancer Genome Atlas databases were subjected to analysis for differentially expressed genes using R software. The identified differentially expressed genes were subjected to gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses followed by construction of protein-protein interaction networks using the STRING database to identify key genes. The genes were further validated via survival and differential gene expression analyses. We identified 97 upregulated and 106 downregulated genes that were primarily associated with processes such as mitosis, protein kinase activity, cell cycle, and the p53 signaling pathway. Visualization of the protein-protein interaction network identified 10 key genes ( CCNA2, CDK1, CDC20, CCNB1, DLGAP5, AURKA, BUB1B, RRM2, TPX2, and MAD2L1), all of which were upregulated. Survival analysis using PROGgeneV2 showed that CDC20, CCNA2, DLGAP5, RRM2, and TPX2 are prognosis-related key genes in HER2+ breast cancer. A nomogram showed that high expression of RRM2, DLGAP5, and TPX2 was positively associated with the risk of death. TPX2, which has not previously been reported in HER2+ breast cancer, was associated with breast cancer development, progression, and prognosis and is therefore a potential key gene. It is hoped that this study can provide a new method for the diagnosis and treatment of HER2 + breast cancer.


2013 ◽  
Vol 171 (2) ◽  
pp. 488-503 ◽  
Author(s):  
P. T. Prathima ◽  
M. Raveendran ◽  
K. K. Kumar ◽  
P. R. Rahul ◽  
V. Ganesh Kumar ◽  
...  

Oncotarget ◽  
2017 ◽  
Vol 8 (27) ◽  
pp. 43967-43977 ◽  
Author(s):  
Zhongju Shi ◽  
Hengxing Zhou ◽  
Bin Pan ◽  
Lu Lu ◽  
Yi Kang ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document