scholarly journals Bioinformatic analysis of differentially expressed genes and pathways in idiopathic pulmonary fibrosis

2021 ◽  
Vol 0 (0) ◽  
pp. 0-0
Author(s):  
Nana Li ◽  
Lingxiao Qiu ◽  
Cheng Zeng ◽  
Zeming Fang ◽  
Shanshan Chen ◽  
...  
2020 ◽  
Author(s):  
Shuaijun Chen ◽  
Jun Zhang ◽  
Wanli Ma ◽  
Hong Ye

Abstract BackgroundIdiopathic pulmonary fibrosis (IPF) is a relentlessly progressive and fatal fibrotic lung disease all over the world, and specific pathogenesis is still not well understood. DNA methylation is an essential epigenetic mechanism, which likely contributes to the progress of IPF. The purpose of this study is to identify aberrantly methylated differentially expressed genes (DEGs) in IPF and to explore the underlying mechanisms of IPF by using integrated bioinformatics analysis.MethodGene expression profiles and gene methylation profile were downloaded and analyzed to identify the aberrantly methylated‐differentially expressed genes. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Search Tool for the Retrieval of Interacting Genes Database (STRING) and Gene set enrichment analysis (GSEA) were used to evaluate function of DEGs. RT-PCR was used to verify the mRNA levels of DEGs in mice with pulmonary fibrosis.ResultsBy analyzing the differentially expressed genes of the three IPF expression profiles, and taking the intersection, we got 143 co-upregulated genes and 104 co-downregulated genes; GO and KEGG pathway analysis of the DEGs suggested these genes involved in the extracellular matrix organization, multicellular organismal homeostasis. Combining the sequencing data of two IPF methylation chips, we have identified genes that may be regulated by methylation in IPF. Finally, we obtained the mRNA expression of DEGs using a mouse model of pulmonary fibrosis.ConclusionThrough integrated analysis and experimental verification, we found a series of biomarkers which were regulated by methylation should be potential therapeutic targets for IPF.


2021 ◽  
Author(s):  
Shuaijun Chen ◽  
Jun Zhang ◽  
Wanli Ma ◽  
Hong Ye

Abstract Background Idiopathic pulmonary fibrosis (IPF) is a relentlessly progressive and fatal fibrotic lung disease all over the world, and specific pathogenesis is still not well understood. DNA methylation is an essential epigenetic mechanism, which likely contributes to the progress of IPF. The purpose of this study is to identify aberrantly methylated differentially expressed genes (DEGs) in IPF and to explore the underlying mechanisms of IPF by using integrated bioinformatics analysis.Methods Gene expression profiles and gene methylation profiles were downloaded and analyzed to identify the aberrantly methylated‐differentially expressed genes. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Search Tool for the Retrieval of Interacting Genes Database (STRING), and Gene set enrichment analysis (GSEA) were used to evaluate the function of DEGs. RT-PCR was used to verify the mRNA levels of DEGs in mice with pulmonary fibrosis.Results By analyzing the differentially expressed genes of the three IPF expression profiles, and taking the intersection, we got 143 co-upregulated genes and 104 co-downregulated genes; GO and KEGG pathway analysis of the DEGs suggested these genes involved in the extracellular matrix organization, multicellular organismal homeostasis. Combining the sequencing data of two IPF methylation chips, we have identified genes that may be regulated by methylation in IPF. Finally, we obtained the mRNA expression of DEGs using a mouse model of pulmonary fibrosis.Conclusions Through integrated analysis and experimental verification, we found a series of biomarkers that were regulated by methylation should be potential therapeutic targets for IPF.


2019 ◽  
Vol 20 (8) ◽  
pp. 1958 ◽  
Author(s):  
Ming-Ju Tsai ◽  
Wei-An Chang ◽  
Ssu-Hui Liao ◽  
Kuo-Feng Chang ◽  
Chau-Chyun Sheu ◽  
...  

Idiopathic pulmonary fibrosis (IPF) is a disabling and lethal chronic progressive pulmonary disease. Epigallocatechin gallate (EGCG) is a polyphenol, which is the major biological component of green tea. The anti-oxidative, anti-inflammatory, and anti-fibrotic effects of EGCG have been shown in some studies, whereas its effects in altering gene expression in pulmonary fibroblasts have not been systematically investigated. This study aimed to explore the effect of EGCG on gene expression profiles in fibroblasts of IPF. The pulmonary fibroblasts from an IPF patient were treated with either EGCG or water, and the expression profiles of mRNAs and microRNAs were determined by next-generation sequencing (NGS) and analyzed with the bioinformatics approach. A total of 61 differentially expressed genes and 56 differentially expressed microRNAs were found in EGCG-treated IPF fibroblasts. Gene ontology analyses revealed that the differentially expressed genes were mainly involved in the biosynthetic and metabolic processes of cholesterol. In addition, five potential altered microRNA–mRNA interactions were found, including hsa-miR-939-5p–PLXNA4, hsa-miR-3918–CTIF, hsa-miR-4768-5p–PDE5A, hsa-miR-1273g-3p–VPS53, and hsa-miR-1972–PCSK9. In summary, differentially expressed genes and microRNAs in response to EGCG treatment in IPF fibroblasts were identified in the current study. Our findings provide a scientific basis to evaluate the potential benefits of EGCG in IPF treatment, and warrant future studies to understand the role of molecular pathways underlying cholesterol homeostasis in the pathogenesis of IPF.


2018 ◽  
Vol 46 (5) ◽  
pp. 1868-1878 ◽  
Author(s):  
Ming-Yu Huang ◽  
Wen-Qian Zhang ◽  
Miao Zhao ◽  
Can Zhu ◽  
Jia-Peng He ◽  
...  

Background/Aims: The mouse is widely used as an animal model for studying human embryo implantation. However, the mouse is unique in that both ovarian progesterone and estrogen are critical to implantation, whereas in the majority of species (e.g. human and hamster) implantation can occur in the presence of progesterone alone. Methods: In this study, we analyzed embryo-induced transcriptomic changes in the hamster uterus during embryo implantation by using RNA-seq. Differentially expressed genes were characterized by bioinformatic analysis. Results: We identified a total of 781 differentially expressed genes, of which 367 genes were up-regulated and 414 genes were down-regulated at the implantation site compared to the inter-implantation site. Functional clustering and gene network analysis highlighted the cell cycle process in uterus upon embryo implantation. By examining of the promoter regions of differentially expressed genes, we identified 7 causal transcription factors. Additionally, through connectivity map (CMap) analysis, multiple compounds were identified to have potential anti-implantation effects due to their ability to reverse embryo-induced transcriptomic changes. Conclusion: Our study provides a valuable resource for in-depth understanding of the mechanism underlying embryo implantation.


2020 ◽  
Vol 16 (8) ◽  
pp. 1205-1218
Author(s):  
Wei Li ◽  
Aiqin Nie ◽  
Qiang Li ◽  
He Cao ◽  
Yinwei Song ◽  
...  

Recent studies have found that chromosome 3 is frequently mutated in metastatic uveal melanoma (UVM), which leads to the loss of BAP1 expression or the weakening of BRCA1-associated protein 1 (BAP1) function and promotes metastasis of uveal melanoma cells. However, the specific signaling pathways that are affected by BAP1 depletion in uveal melanoma remain unclear. Our aim in this study was to verify the effect and regulatory mechanism of BAP1 on uveal melanoma. RT-qPCR and western blotting results showed that BAP1 was significantly down-regulated in OCM-1A cells treated with a BAP1 shRNA vector. MTT, cell scratch and transwell migration assays showed that low expression of BAP1 significantly promoted the proliferation and migration of UVM cells. A total of 269 up-regulated and 807 down-regulated genes were identified from the combined GSE110193 and GSE48863 data sets. These differentially expressed genes are mainly involved in the composition of extracellular matrix and the regulation of the Wnt signaling pathway and are closely related to the cell adhesion pathway. CXCL8, COL5A3, COL11A1, and COL12A1 were among the differentially expressed genes and are closely related to the prognosis of UVM. Therefore, the deletion of BAP1 is closely related to poor prognosis of UVM and is a risk factor for UVM metastasis. The potential targets of BAP1 include CXCL8, COL5A3, COL11A1, and COL12A1. It is believed that BAP1 regulates UVM cell adhesion through these four genes and ultimately regulates tumor development and migration.


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