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Identification of hub genes of pneumocyte senescence induced by thoracic irradiation using weighted gene co?expression network analysis.

ABSTRACT: Irradiation commonly causes pneumocyte senescence, which may lead to severe fatal lung injury characterized by pulmonary dysfunction and respiratory failure. However, the molecular mechanism underlying the induction of pneumocyte senescence by irradiation remains to be elucidated. In the present study, weighted gene co?expression network analysis (WGCNA) was used to screen for differentially expressed genes, and to identify the hub genes and gene modules, which may be critical for senescence. A total of 2,916 differentially expressed genes were identified between the senescence and non?senescence groups following thoracic irradiation. In total, 10 gene modules associated with cell senescence were detected, and six hub genes were identified, including B?cell scaffold protein with ankyrin repeats 1, translocase of outer mitochondrial membrane 70 homolog A, actin filament?associated protein 1, Cd84, Nuf2 and nuclear factor erythroid 2. These genes were markedly associated with cell proliferation, cell division and cell cycle arrest. The results of the present study demonstrated that WGCNA of microarray data may provide further insight into the molecular mechanism underlying pneumocyte senescence.

SUBMITTER: Xing Y

PROVIDER: S-EPMC4686054 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

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Identification of hub genes of pneumocyte senescence induced by thoracic irradiation using weighted gene co‑expression network analysis.

Xing Yonghua Y Zhang Junling J Lu Lu L Li Deguan D Wang Yueying Y Huang Song S Li Chengcheng C Zhang Zhubo Z Li Jianguo J Meng Aimin A

Molecular medicine reports 20151113 1

Irradiation commonly causes pneumocyte senescence, which may lead to severe fatal lung injury characterized by pulmonary dysfunction and respiratory failure. However, the molecular mechanism underlying the induction of pneumocyte senescence by irradiation remains to be elucidated. In the present study, weighted gene co‑expression network analysis (WGCNA) was used to screen for differentially expressed genes, and to identify the hub genes and gene modules, which may be critical for senescence. A ...[more]

PMID: 26572216

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Project description:ObjectiveTo investigate the differential expression gene modules and hub genes associated with Alzheimer's disease (AD) by weighted gene co-expression network analysis (WGCNA) and annotate the biological functions of these modules.MethodsWe downloaded transcriptome sequencing data from the GEO database, and according to the correlation of the genes, a gene co-expression network was constructed with the parameter setting of β=8 and a correlation coefficient threshold of 0.85. Pearson correlation test was used to calculate the correlation between the module genes and clinical traits to screen the gene modules significantly associated with AD and identify the hub genes according to the connectivity within modules. GO functional enrichment analysis and KEGG pathway analysis were used to annotate the functions of the modules. A cell model of AD was established in SH-SY5Y cells by Aβ1-42 treatment, and the mRNA expression levels of the hub genes were compared between the Aβ1-42-treated cells and the control cells.ResultsTen gene co-expression modules were constructed based on the correlations of gene expression, in which the brown (r=0.66, P < 0.001) and turquoise modules (r=-0.68, P < 0.001) were significantly correlated with the AD group. Forty-eight genes were identified as the hub genes in the co-expression network. Function annotation revealed that the genes in both modules were mainly enriched in DNA damage and repair pathways and metabolism-related pathways. Differential expression analysis of the genes revealed that the genes DNASE1, TEKT2 and MTSS1L were highly expressed while ACP2, LANCL2 and GMPR2 were lowly expressed in AD group. The results of cell experiment confirmed the up-regulation of DNASE1, TEKT2 and MTSS1L genes and the down-regulation of ACP2, LANCL2, and GMPR2 in Aβ1-42-treated SH-SY5Y cells (P < 0.01).ConclusionThe brown and turquoise modules are closely correlated with AD. The hub genes including MTSS1L, GMPR2, ACP2, ACTG1 and LANCL2 selected from the modules may participate in AD pathogenesis by regulating DNA damage and repair.

Dataset Information

Identification of hub genes of pneumocyte senescence induced by thoracic irradiation using weighted gene co?expression network analysis.

Publications

Identification of hub genes of pneumocyte senescence induced by thoracic irradiation using weighted gene co‑expression network analysis.

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