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Investigation of candidate genes and mechanisms underlying postmenopausal osteoporosis using bioinformatics analysis.

ABSTRACT: The present study aimed to determine candidate genes, chemicals and mechanisms underlying postmenopausal osteoporosis (PMOP). A gene expression profile (accession no. GSE68303), which included 12 tissue samples from ovariectomized mice (OVX group) and 11 normal tissue samples from sham surgery mice (control group), was downloaded from the Gene Expression Omnibus database. The identification of differentially expressed genes (DEGs), and Gene Ontology functional enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analyses, was performed, followed by an investigation of protein?protein interactions (PPI), PPI modules, transcription factors (TFs) and chemicals. A total of 784 upregulated and 729 downregulated DEGs between the two groups were identified. Furthermore, 2 upregulated modules and 6 downregulated modules were determined. The upregulated DEGs in modules were enriched in 'sensory perception of smell' function and 'olfactory transduction' pathway, and a number of genes belonging to the olfactory receptor (OLFR) family were identified in upregulated modules. The downregulated DEGs in modules were enriched in 'DNA replication initiation' function and 'cell cycle' pathway. A total of 8 TFs, including SP1 TF (SP1) and protein C?ets?1 (ETS1), were associated with PMOP. Furthermore, estradiol and resveratrol were identified as key chemicals in the chemical?gene interaction network. Therefore, TFs, including SP1 and ETS1, in addition to members of the OLFR gene family, may be employed as novel targets for treatment of PMOP. Furthermore, functions including 'sensory perception of smell' and 'replication initiation', and 'olfactory transduction' and 'cell cycle' pathways, may serve roles in PMOP. In addition, based on the chemical?gene interaction network, estradiol and resveratrol may also be considered for the treatment PMOP.

SUBMITTER: Zhu X

PROVIDER: S-EPMC5780095 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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Investigation of candidate genes and mechanisms underlying postmenopausal osteoporosis using bioinformatics analysis.

Zhu Xiaozhong X Wang Zhiyuan Z Zhao Yanxun Y Jiang Chao C

Molecular medicine reports 20171114 1

The present study aimed to determine candidate genes, chemicals and mechanisms underlying postmenopausal osteoporosis (PMOP). A gene expression profile (accession no. GSE68303), which included 12 tissue samples from ovariectomized mice (OVX group) and 11 normal tissue samples from sham surgery mice (control group), was downloaded from the Gene Expression Omnibus database. The identification of differentially expressed genes (DEGs), and Gene Ontology functional enrichment and Kyoto Encyclopedia o ...[more]

PMID: 29138843

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Project description:BackgroundObesity associated type 2 diabetes mellitus is a metabolic disorder ; however, the etiology of obesity associated type 2 diabetes mellitus remains largely unknown. There is an urgent need to further broaden the understanding of the molecular mechanism associated in obesity associated type 2 diabetes mellitus.MethodsTo screen the differentially expressed genes (DEGs) that might play essential roles in obesity associated type 2 diabetes mellitus, the publicly available expression profiling by high throughput sequencing data (GSE143319) was downloaded and screened for DEGs. Then, Gene Ontology (GO) and REACTOME pathway enrichment analysis were performed. The protein - protein interaction network, miRNA - target genes regulatory network and TF-target gene regulatory network were constructed and analyzed for identification of hub and target genes. The hub genes were validated by receiver operating characteristic (ROC) curve analysis and RT- PCR analysis. Finally, a molecular docking study was performed on over expressed proteins to predict the target small drug molecules.ResultsA total of 820 DEGs were identified between healthy obese and metabolically unhealthy obese, among 409 up regulated and 411 down regulated genes. The GO enrichment analysis results showed that these DEGs were significantly enriched in ion transmembrane transport, intrinsic component of plasma membrane, transferase activity, transferring phosphorus-containing groups, cell adhesion, integral component of plasma membrane and signaling receptor binding, whereas, the REACTOME pathway enrichment analysis results showed that these DEGs were significantly enriched in integration of energy metabolism and extracellular matrix organization. The hub genes CEBPD, TP73, ESR2, TAB1, MAP 3K5, FN1, UBD, RUNX1, PIK3R2 and TNF, which might play an essential role in obesity associated type 2 diabetes mellitus was further screened.ConclusionsThe present study could deepen the understanding of the molecular mechanism of obesity associated type 2 diabetes mellitus, which could be useful in developing therapeutic targets for obesity associated type 2 diabetes mellitus.

Project description:BACKGROUND:Familial hypercholesterolemia (FH) is one of the commonest inherited metabolic disorders. Abnormally high level of low-density lipoprotein cholesterol (LDL-C) in blood leads to premature atherosclerosis onset and a high risk of cardiovascular disease (CVD). However, the specific mechanisms of the progression process are still unclear. Our study aimed to investigate the potential differently expressed genes (DEGs) and mechanism of FH using various bioinformatic tools. METHODS:GSE13985 and GSE6054 were downloaded from the Gene Expression Omnibus (GEO) database for bioinformatic analysis in this study. First, limma package of R was used to identify DEGs between blood samples of patients with FH and those from healthy individuals. Then, the functional annotation of DEGs was carried out by Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and Gene Ontology (GO) analysis. Based on Search Tool for the Retrieval of Interacting Genes (STRING) tool, we constructed the Protein-Protein Interactions (PPIs) network among DEGs and mined the core genes as well. RESULTS:A total of 102 communal DEGs (49 up-regulated and 53 down-regulated) are identified in FH samples compared with control samples. The functional changes of DEGs are mainly associated with the focal adhere and glucagon signaling pathway. Ten genes (ITGAL, TLN1, POLR2A, CD69, GZMA, VASP, HNRNPUL1, SF1, SRRM2, ITGAV) were identified as core genes. Bioinformatic analysis showed that the core genes are mainly enriched in numerous processes related to cell adhesion, integrin-mediated signaling pathway and cell-matrix adhesion. In the transcription factor (TF) target regulating network, 219 nodes were detected, including 214 DEGs and 5 TFs (SP1, EGR3, CREB, SEF1, HOX13). In conclusion, the DEGs and hub genes identified in this study may help us understand the potential etiology of the occurrence and development of AS. CONCLUSION:Up-regulated ITGAL, TLN1, POLR2A, VASP, HNRNPUL1, SF1, SRRM2, and down-regulated CD69, GZMA and ITGAV performed important promotional effects for the formation of atherosclerotic plaques those suffering from FH. Moreover, SP1, EGR3, CREB, SEF1 and HOX13 were the potential transcription factors for DEGs and could serve as underlying targets for AS rupture prevention. These findings provide a theoretical basis for us to understand the potential etiology of the occurrence and development of AS in FH patients and we may be able to find potential diagnostic and therapeutic targets.

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Investigation of candidate genes and mechanisms underlying postmenopausal osteoporosis using bioinformatics analysis.

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Investigation of candidate genes and mechanisms underlying postmenopausal osteoporosis using bioinformatics analysis.

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