Identification of Signal Pathways and Hub Genes of Pulmonary Arterial Hypertension by Bioinformatic Analysis

Wei, Rui-Qi; Zhang, Wenmei; Liang, Zhe; Piao, Chunmei; Zhu, Guangfa

doi:10.1155/2022/1394088

Cited by 7 publications

(10 citation statements)

References 41 publications

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“…As shown in previous reports, the GO terms and KEGG pathways that hsa_circ_0007608 and hsa_circ_0064656 were enriched in were all related to the occurrence and regulation processes of PH. It is obvious that intracellular signal transduction is ubiquitous in the pathogenesis of PH in COPD [36] . Existing studies also show that ECM is implicated in the development of pulmonary vascular remodeling and high level of ECM-related proteins such as MMP-2 are associated with poor survival and prognosis of PH patients [37] .…”

Section: Discussionmentioning

confidence: 99%

“…Bioinformatics tools has been widely applied in oncology to identify genetic changes and new potential biomarkers associated with various diseases [14][15][16] . Likewise, researchers have tried to apply bioinformtics analysis in the study of PH to to elucidate the potential functions of circRNAs related to PH, mostly based on databases and animal experiments [17][18][19][20][21][22][23][24][25][26] . However, few studies have utilized clinical samples with definite diagnosis of PH, and researches for PH in COPD are even fewer.…”

Section: W I T H D R a W N S E E M A N U S C R I P T D O I F O R D E ...mentioning

confidence: 99%

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Expression profiles of circRNAs and identification of hsa_circ_0007608 and hsa_circ_0064656 as potential biomarkers for COPD-PH patients

HUANG

Shen

et al. 2023

Preprint

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Pulmonary hypertension(PH) is a common complication of chronic obstructive pulmonary disease(COPD) which can worsen the prognosis and increase the mortality of COPD patients. However, the underlying mechanisms of PH in COPD(COPD-PH) remain to be elucidated. This study is the first to explore the expression profile of circRNAs in human lung tissues with definite diagnosis of COPD-PH and validate the differentially expressed circRNAs(DECs) utilizing human serum, pulmonary arterial endothelial cells(HPAECs) and pulmonary arterial smooth muscle cells(HPASMCs). A total of 136 circRNAs(39 up-regulated and 97 down-regulated) were differentially expressed between the COPD-PH group and the control group. Following quantitative real-time polymerase chain reaction(qRT-PCR) validation, two circRNAs (hsa_circ_0007608 and hsa_circ_0064656) were believed to be involved in the pathogenesis. GO and KEGG pathway analysis suggested these two DECs were mainly related to the celluar proliferation, migration and EndoMT. PPI network revealed 11 pairs of key mRNAs. VCAM1, VCAN and THBS1, three hub mRNAs with the highest reliability among all, were validated and proven to be up-regulated in COPD-PH. We innovatively found that VCAN may be involved in COPD-PH. These identified genes show high potential to be diagnostic markers and therapeutic targets of COPD-PH, and may provide new insights into the underlying mechanisms of COPD-PH patients.

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Section: Discussionmentioning

confidence: 99%

Section: W I T H D R a W N S E E M A N U S C R I P T D O I F O R D E ...mentioning

confidence: 99%

Expression profiles of circRNAs and identification of hsa_circ_0007608 and hsa_circ_0064656 as potential biomarkers for COPD-PH patients

HUANG

Shen

et al. 2023

Preprint

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“…More and more researchers have extended this method to the field of PAH and achieved some important results [ 11 , 12 ]. However, most of these studies are limited to the theoretical stage without experimental verification [ 15 , 16 ].…”

Section: Discussionmentioning

confidence: 99%

“…Lin W et al found that TXNRD1 as a novel biomarker and potential therapeutic target for IPAH through Robust Rank Aggregation (RRA) method and experiments [ 14 ]. However, some of the current studies have the shortcomings of only making theoretical predictions and not further verifying the reliability of their prediction results through experiments [ 15 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

NCAPG Promotes Pulmonary Artery Smooth Muscle Cell Proliferation as a Promising Therapeutic Target of Idiopathic Pulmonary Hypertension: Bioinformatics Analysis and Experiment Verification

Shi

et al. 2022

IJMS

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Idiopathic pulmonary arterial hypertension (IPAH) is a disease with complex etiology. Currently, IPAH treatment is limited, and patients’ prognosis is poor. This study aimed to explore new therapeutic targets in IPAH through bioinformatics. Two data sets (GSE113439 and GSE130391) meeting the requirements were obtained from the Gene Expression Omnibus (GEO) database. Then, differentially expressed genes (DEGs) were identified and analyzed by NetworkAnalyst platform. By enriching Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG), we examined the function of DEGs. A protein–protein interaction (PPI) network was constructed to identify central genes using the CytoNCA plug-in. Finally, four central genes, ASPM, CENPE, NCAPG, and TOP2A, were screened out. We selected NCAPG for protein-level verification. We established an animal model of PAH and found that the expression of NCAPG was significantly increased in the lung tissue of PAH rats. In vitro experiments showed that the expression of NCAPG was significantly increased in proliferative pulmonary arterial smooth muscle cells (PASMCs). When NCAPG of PASMCs was knocked down, the cell proliferation was inhibited, which suggested that NCAPG was related to the proliferation of PASMCs. Therefore, these results may provide new therapeutic targets for IPAH.

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“…We removed probe IDs that lacked corresponding gene symbols, and for genes with multiple probes, the highest value was considered the gene expression value. The gene expression matrix obtained was subjected to additional quality control through cluster and principal component analysis (PCA) [14] .…”

Section: Data Handlingmentioning

confidence: 99%

Bioinformatics analysis reveals link between alternative complement cascade pathway and colorectal cancer liver metastasis

Shi,

Li,

Wei

et al. 2023

Preprint

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Background Colorectal cancer (CRC) has a high incidence mortality rate and is characterized by liver metastasis, which is the main cause of CRC patient death. In this study, a transcriptome sequencing dataset (GSE81558) from the integrated Gene Expression Omnibus database was evaluated to gain new insights into the pathogenesis of CRC and potential therapeutic targets. Methods All raw data were processed using R and screened for differentially expressed genes (DEGs) using LIMMA software. In-depth Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were conducted and visualized using R and Cytoscape software. Protein‒protein interactions (PPIs) associated with the DEGs were assessed using the Search Tool for the Retrieval of Interacting Genes/Proteins database. A mouse model of CRC liver metastasis of CRC was used to verify key associated signaling pathways. Results The GO biological processes (BPs) and KEGG pathway analyses revealed that DEGs between the normal colon and CRC samples were mainly involved in the cell cycle and the P53 signaling pathway, which regulate the cell cycle and alter tumor signaling pathways. The 10 hub genes identified by PPI were cell cycle-related. In CRC versus and CRC liver metastasis samples, the GO BPs were mainly associated with platelets and coagulation, and the KEGG pathways were mainly enriched in the complement and coagulation cascades and drug metabolism. The PPI hub genes were blood protein-related, such as ALB, AHSG, and APOH, or plasma protease inhibitors, such as SERPINC1. To confirm bioinformatics analysis results, we used wild-type (WT), C4 (an important molecule in the classical and lectin complement cascade pathways), and complement factor B (fB, an important molecule in the alternative complement cascade pathway) knockout (KO) mice to construct a CRC liver metastasis model. Compared with WT mice, fB-KO mice demonstrated significantly reduced liver metastasis and inflammation, while there was no difference in C4-KO mice. Conclusion Bioinformatics analyses revealed that the complement cascade is related to CRC liver metastasis and that the cell cycle is related to CRC. The role of the alternative complement pathway in CRC liver metastasis was confirmed in mice, indicating that this pathway is a potential therapeutic target in CRC liver metastasis and providing a theoretical basis for further research.

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Identification of Signal Pathways and Hub Genes of Pulmonary Arterial Hypertension by Bioinformatic Analysis

Cited by 7 publications

References 41 publications

Expression profiles of circRNAs and identification of hsa_circ_0007608 and hsa_circ_0064656 as potential biomarkers for COPD-PH patients

Expression profiles of circRNAs and identification of hsa_circ_0007608 and hsa_circ_0064656 as potential biomarkers for COPD-PH patients

NCAPG Promotes Pulmonary Artery Smooth Muscle Cell Proliferation as a Promising Therapeutic Target of Idiopathic Pulmonary Hypertension: Bioinformatics Analysis and Experiment Verification

Bioinformatics analysis reveals link between alternative complement cascade pathway and colorectal cancer liver metastasis

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