scholarly journals Comprehensive Analysis of Hub Genes Associated With Competing Endogenous RNA Networks in Stroke Using Bioinformatics Analysis

2022 ◽  
Vol 12 ◽  
Author(s):  
Xiuqi Chen ◽  
Danhong Wu

Background: Acute ischemic stroke (AIS) is the second leading cause of death and the third leading cause of disability worldwide. Long noncoding RNAs (lncRNAs) are promising biomarkers for the early diagnosis of AIS and closely participate in the mechanism of stroke onset. However, studies focusing on lncRNAs functioning as microRNA (miRNA) sponges to regulate the mRNA expression are rare and superficial.Methods: In this study, we systematically analyzed the expression profiles of lncRNA, mRNA (GSE58294), and miRNA (GSE110993) from the GEO database. Gene ontology (GO) analysis was performed to reveal the functions of differentially expressed genes (DEGs), and we used weighted gene co-expression network analysis (WGCNA) to investigate the relationships between clinical features and expression profiles and the co-expression of miRNA and lncRNA. Finally, we constructed a lncRNA–miRNA–mRNA competing endogenous RNA (ceRNA) network with selected DEGs using bioinformatics methods and obtained ROC curves to assess the diagnostic efficacy of differentially expressed lncRNAs (DElncRNAs) and differentially expressed mRNAs (DEmRNAs) in our network. The GSE22255 dataset was used to confirm the diagnostic value of candidate genes.Results: In total, 199 DElncRNAs, 2068 DEmRNAs, and 96 differentially expressed miRNAs were detected. The GO analysis revealed that DEmRNAs primarily participate in neutrophil activation, neutrophil degranulation, vacuolar transport, and lysosomal transport. WGCNA screened out 16 lncRNAs and 195 mRNAs from DEGs, and only eight DElncRNAs maintained an area under the curve higher than 0.9. By investigating the relationships between lncRNAs and mRNAs, a ceRNA network containing three lncRNAs, three miRNAs, and seven mRNAs was constructed. GSE22255 confirmed that RP1-193H18.2 is more advantageous for diagnosing stroke, whereas no mRNA showed realistic diagnostic efficacy.Conclusion: The ceRNA network may broaden our understanding of AIS pathology, and the candidate lncRNA from the ceRNA network is assumed to be a promising therapeutic target and diagnostic biomarker for AIS.

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Xuefeng Gu ◽  
Dongyang Jiang ◽  
Yue Yang ◽  
Peng Zhang ◽  
Guoqing Wan ◽  
...  

Background. Moyamoya disease (MMD) is a rare cerebrovascular disease characterized by chronic progressive stenosis or occlusion of the bilateral internal carotid artery (ICA), the anterior cerebral artery (ACA), and the middle cerebral artery (MCA). MMD is secondary to the formation of an abnormal vascular network at the base of the skull. However, the etiology and pathogenesis of MMD remain poorly understood. Methods. A competing endogenous RNA (ceRNA) network was constructed by analyzing sample-matched messenger RNA (mRNA), long non-coding RNA (lncRNA), and microRNA (miRNA) expression profiles from MMD patients and control samples. Then, a protein-protein interaction (PPI) network was constructed to identify crucial genes associated with MMD. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses were employed with the DAVID database to investigate the underlying functions of differentially expressed mRNAs (DEmRNAs) involved in the ceRNA network. CMap was used to identify potential small drug molecules. Results. A total of 94 miRNAs, 3649 lncRNAs, and 2294 mRNAs were differentially expressed between MMD patients and control samples. A synergistic ceRNA lncRNA-miRNA-mRNA regulatory network was constructed. Core regulatory miRNAs (miR-107 and miR-423-5p) and key mRNAs (STAT5B, FOSL2, CEBPB, and CXCL16) involved in the ceRNA network were identified. GO and KEGG analyses indicated that the DEmRNAs were involved in the regulation of the immune system and inflammation in MMD. Finally, two potential small molecule drugs, CAY-10415 and indirubin, were identified by CMap as candidate drugs for treating MMD. Conclusions. The present study used bioinformatics analysis of candidate RNAs to identify a series of clearly altered miRNAs, lncRNAs, and mRNAs involved in MMD. Furthermore, a ceRNA lncRNA-miRNA-mRNA regulatory network was constructed, which provides insights into the novel molecular pathogenesis of MMD, thus giving promising clues for clinical therapy.


2020 ◽  
Vol 9 (3) ◽  
pp. 90-98 ◽  
Author(s):  
Haitao Chen ◽  
Liaobin Chen

Aims This study aimed to uncover the hub long non-coding RNAs (lncRNAs) differentially expressed in osteoarthritis (OA) cartilage using an integrated analysis of the competing endogenous RNA (ceRNA) network and co-expression network. Methods Expression profiles data of ten OA and ten normal tissues of human knee cartilage were obtained from the Gene Expression Omnibus (GEO) database (GSE114007). The differentially expressed messenger RNAs (DEmRNAs) and lncRNAs (DElncRNAs) were identified using the edgeR package. We integrated human microRNA (miRNA)-lncRNA/mRNA interactions with DElncRNA/DEmRNA expression profiles to construct a ceRNA network. Likewise, lncRNA and mRNA expression profiles were used to build a co-expression network with the WGCNA package. Potential hub lncRNAs were identified based on an integrated analysis of the ceRNA network and co-expression network. StarBase and Multi Experiment Matrix databases were used to verify the lncRNAs. Results We detected 1,212 DEmRNAs and 49 DElncRNAs in OA and normal knee cartilage. A total of 75 dysregulated lncRNA-miRNA interactions and 711 dysregulated miRNA-mRNA interactions were obtained in the ceRNA network, including ten DElncRNAs, 69 miRNAs, and 72 DEmRNAs. Similarly, 1,330 dysregulated lncRNA-mRNA interactions were used to construct the co-expression network, which included ten lncRNAs and 407 mRNAs. We finally identified seven hub lncRNAs, named MIR210HG, HCP5, LINC00313, LINC00654, LINC00839, TBC1D3P1-DHX40P1, and ISM1-AS1. Subsequent enrichment analysis elucidated that these lncRNAs regulated extracellular matrix organization and enriched in osteoclast differentiation, the FoxO signalling pathway, and the tumour necrosis factor (TNF) signalling pathway in the development of OA. Conclusion The integrated analysis of the ceRNA network and co-expression network identified seven hub lncRNAs associated with OA. These lncRNAs may regulate extracellular matrix changes and chondrocyte homeostasis in OA progress. Cite this article: Bone Joint Res. 2020;9(3):90–98.


2020 ◽  
Vol 2020 ◽  
pp. 1-10 ◽  
Author(s):  
Xue Wang ◽  
Chundi Gao ◽  
Fubin Feng ◽  
Jing Zhuang ◽  
Lijuan Liu ◽  
...  

Background. Long noncoding RNAs (lncRNAs) act as competing endogenous RNAs for microRNAs in cancer metastasis. However, the roles of lncRNA-mediated competing endogenous RNA (ceRNA) networks for breast cancer (BC) are still unclear. Material and Methods. The expression profiles of mRNAs, lncRNAs, and miRNAs with BC were extracted from The Cancer Genome Atlas database. Weighted gene coexpression network analysis was conducted to extract differentially expressed mRNAs (DEmRNAs) that might be core genes. Through miRWalk, TargetScan, and miRDB to predict the target genes, an abnormal lncRNA-miRNA-mRNA ceRNA network with BC was constructed. The survival possibilities of mRNAs, miRNAs, and lncRNAs for patients with BC were determined by Kaplan-Meier survival curves and Oncomine. Results. We identified 2134 DEmRNAs, 1059 differentially expressed lncRNAs (DElncRNAs), and 86 differentially expressed miRNAs (DEmiRNAs). We then compose a ceRNA network for BC, including 72 DElncRNAs, 8 DEmiRNAs, and 12 DEmRNAs. After verification, 2 lncRNAs (LINC00466, LINC00460), 1 miRNA (Hsa-mir-204), and 5 mRNAs (TGFBR2, CDH2, CHRDL1, FGF2, and CHL1) were meaningful as prognostic biomarkers for BC patients. In the ceRNA network, we found that three axes were present in 10 RNAs related to the prognosis of BC, namely, LINC00466-Hsa-mir-204-TGFBR2, LINC00466-Hsa-mir-204-CDH2, and LINC00466-Hsa-mir-204-CHRDL1. Conclusion. This study highlighted lncRNA-miRNA-mRNA ceRNA related to the pathogenesis of BC, which might be used for latent diagnostic biomarkers and therapeutic targets for BC.


2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Zhan Zhang ◽  
Ping Wang ◽  
Linlin Zhang ◽  
Chenxi Huang ◽  
Junjun Gao ◽  
...  

Background. Preeclampsia (PE) is a pregnancy-specific hypertension syndrome and is one of the leading causes of maternal and perinatal morbidity and mortality. Long noncoding RNAs (lncRNAs) have been reported to be abnormally expressed in many diseases, including preeclampsia. The present study is aimed at identifying the key genes and lncRNA-associated competing endogenous RNA (ceRNA) networks in early-onset preeclampsia (EOPE). Methods. We investigated expression profiles of differentially expressed lncRNAs (DElncRNAs) and genes (DEGs) in placental tissues of EOPE and healthy controls with Human LncRNA Array v4. The potential functions of DEGs and DElncRNAs were predicted using the clusterProfiler package. The lncRNA-mRNA coexpression network was constructed via Pearson’s correlation coefficient. The protein-protein interaction (PPI) network of DEGs was constructed, and the hub genes were obtained using the STRING database and Cytoscape. The ceRNA networks were constructed based on miRWalk and LncBase v2. qRT-PCR was performed to confirm the expression of lncRNA MIR193BHG, PROX1-AS1, and GATA3-AS1. ROC curves were performed to assess the clinical value of lncRNA MIR193BHG, PROX1-AS1, and GATA3-AS1 in the diagnosis of EOPE. Results. We found 6 hub genes (SPP1, CCR2, KIT, ENG, ACKR1, and FLT1) altered in placental tissues of EOPE and constructed a ceRNA network, including 21 lncRNAs, 3 mRNAs, and 69 miRNAs. The expression of lncRNA MIR193BHG and GATA3-AS1 were elevated and showed good clinical values for diagnosing EOPE. Conclusion. This study provides novel insights into the lncRNA-related ceRNA network in EOPE and identified two lncRNAs as potential prognostic biomarkers in EOPE.


2021 ◽  
Author(s):  
Yuhua Chen ◽  
Hao Zhou ◽  
Zhendong Wang ◽  
Zhanghao Huang ◽  
Jinjie Wang ◽  
...  

Background. Esophageal cancer (ESCA) is one of the most commonly diagnosed cancers in the world. Tumor immune microenvironment is closely related to tumor prognosis. This study aimed at analyzing the competing endogenous RNA (ceRNA) network and tumor-infiltrating immune cells in ESCA. Methods. The expression profiles of mRNAs, lncRNAs, and miRNAs were downloaded from the Cancer Genome Atlas database. A ceRNA network was established based on the differentially expressed RNAs by Cytoscape. CIBERSORT was applied to estimate the proportion of immune cells in ESCA. Prognosis-associated genes and immune cells were applied to establish prognostic models basing on Lasso and multivariate Cox analyses. The survival curves were constructed with Kaplan-Meier method. The predictive efficacy of the prognostic models was evaluated by the receiver operating characteristic (ROC) curves. Results. The differentially expressed mRNAs, lncRNAs, and miRNAs were identified. We constructed the ceRNA network including 23 lncRNAs, 19 miRNAs and 147 mRNAs. Five key molecules (HMGB3, HOXC8, HSPA1B, KLHL15, and RUNX3) were identified from the ceRNA network and five significant immune cells (Plasma cells, T cells follicular helper, Monocytes, Dendritic cells activated, and Neutrophils) were selected via CIBERSORT. The ROC curves based on key genes and significant immune cells all showed good sensitivity (AUC of 3-year survival: 0.739, AUC of 5-year survival: 0.899, AUC of 3-year survival: 0.824, AUC of 5-year survival: 0.876). There was certain correlation between five immune cells and five key molecules. Conclusion. This study provides an effective bioinformatics basis for exploring the potential biomarkers of ESCA and predicting its prognosis.


PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e10395
Author(s):  
Haiyang Liu ◽  
Di Liu ◽  
Yexin Liu ◽  
Ming Xia ◽  
Yan Li ◽  
...  

Background Immunoglobulin A nephropathy (IgAN) is immune-mediated primary glomerulonephritis, which is the most common reason leading to renal failure worldwide. The exact pathogenesis of IgAN is not well defined. Accumulating evidence indicates that circular RNAs (circRNAs) play crucial roles in the immune disease by involving in the competing endogenous RNA (ceRNA) network mechanism. At present, the studies of the circRNA profiles and circRNA-associated ceRNA networks in the IgAN are still scarce. This study aimed to elucidate the potential roles of circRNA-associated ceRNA networks of peripheral blood mononuclear cells (PBMCs) in IgAN patients Method CircRNA sequencing was used to identify the differential expressed circRNAs (DEcircRNAs) of PBMCs in IgAN and healthy controls; limma packages from data sets GSE25590 and GSE73953 in the Gene Expression Omnibus (GEO) database, were used to identify differentially expressed micro RNAs (miRNAs) and message RNAs (mRNAs). A circRNA-miRNA-mRNA ceRNA network was constructed to further investigate the mechanisms of IgAN. Then, GO analysis and KEGG enrichment analyses were used to annotate the genes involved in the circRNA-associated ceRNA network. Further, Protein-protein interaction (PPI) networks were established to screen potential hub genes, by using Search Tool for the Retrieval of Interacting Genes/Proteins (STRING). Last, a quantitative real-time polymerase chain reaction (qRT-PCR) was applied to verify the hub genes in the ceRNA network. Result A total of 145 circRNAs, 22 miRNAs, and 1,117 mRNAs were differentially expressed in IgAN compared with controls (P < 0.05). A ceRNA network was constructed which contained 16 DEcircRNAs, 72 differential expressed mRNAs (DEmRNAs) and 11 differential expressed miRNAs (DEmiRNAs). KEGG pathway enrichment analysis illustrated the underlying biological functions of the ceRNA-associated genes, such as Nitrogen compound metabolic process, COPII-coated ER to Golgi transport vesicle, CAMP response element protein binding process (P < 0.01); meanwhile, Hepatitis B, GnRH signaling, and Prion disease were the most significant enrichment GO terms (P < 0.01). PPI network based on STRING analysis identified 4 potentially hub genes. Finally, Ankyrin repeat and SOCS box containing 16 (ASB16), SEC24 homolog C, COPII coat complex component (SEC24C) were confirmed by qRT-PCR (P < 0.05) and were identified as the hub genes of the ceRNA network in our study. Conclusion Our study identified a novel circRNA-mediated ceRNA regulatory network mechanisms in the pathogenesis of IgAN.


2020 ◽  
Author(s):  
Dan Yang ◽  
Yang He ◽  
Bo Wu ◽  
Yan Deng ◽  
Ruxi Liu ◽  
...  

Abstract Background Lung adenocarcinoma (LUAD) is the most common histological subtype of lung cancer worldwide. Until now, the molecular mechanisms underlying LUAD progression have not been fully explained. This study aimed to identify a competing endogenous RNA (ceRNA) network in LUAD. Methods Differentially expressed lncRNAs (DELs), miRNAs (DEMs), and mRNAs (DEGs) were identified from The Cancer Genome Atlas (TCGA) database with a |log2FC| > 1.0 and a false discovery rate (FDR) < 0.05. Then, these DELs, DEMs, and DEGs were used to construct the initial ceRNA network. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), protein-protein interaction (PPI) network, and survival analyses were performed to analyse these DEGs involved in the ceRNA network. Subsequently, the drug-gene interaction database (DGIdb) was utilized to select candidate LUAD drugs interacting with significant DEGs. Then, lasso-penalized Cox regression and multivariate Cox regression models were used to construct the risk score system. Kaplan-Meier (K-M) survival curves and receiver operating characteristic (ROC) curves were utilized to validate the reliability of the risk score system. Finally, based on the correlations between DELs and DEGs involved in the risk score system, the final ceRNA network was identified. Results A total of 340 DELs, 29 DEMs, and 218 DEGs were selected to construct the initial ceRNA network. Functional enrichment analyses indicated that 218 DEGs were significantly enriched in the GO terms “nucleoplasm”, “transcription factor complex”, “protein binding”, and “metal ion binding”, whereas these DEGs were associated with the KEGG pathway terms “microRNAs in cancer”, “pathways in cancer”, “cell cycle”, “HTLV-1 infection”, and the “PI3K-Akt signalling pathway”. K-M survival analysis of all differentially expressed genes involved in the ceRNA network identified 24 DELs, 4 DEMs, and 29 DEGs, all of which were significantly correlated with LUAD progression (P < 0.05). Furthermore, 15 LUAD drugs interacting with 29 DEGs were selected. After lasso-penalized Cox regression and multivariate Cox regression modelling, 4 DEGs, PRKCE, DLC1, LATS2, and DPY19L1, were incorporated into the risk score system. The area under the curve (AUC) values of the time-dependent ROC curves at 3 years and 5 years were both higher than 0.5. Finally, the correlation coefficients between these 4 DEGs and their corresponding DELs involved in the ceRNA network suggested that there were 2 DEL-DEG pairs, NAV2-AS2 – PRKCE (r = 0.430, P < 0.001) and NAV2-AS2 – LATS2 (r = 0.338, P < 0.001). Considering the previously constructed ceRNA network, NAV2-AS2 – mir-31 – PRKCE and NAV2-SA2 – mir-31 – LATS2 were identified. Conclusions The lncRNA-miRNA-mRNA ceRNA network plays an essential role in LUAD. These results may improve our understanding and provide novel mechanistic insights to explore diagnostics, tumourigenesis, prognosis, and therapeutic drugs for LUAD patients.


BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Siyuan Zhang

Abstract Background As one of the novel molecules, circRNA has been identified closely involved in the pathogenesis of many diseases. However, the function of circRNA in acute myeloid leukemia (AML) still remains unknown. Methods In the current study, the RNA expression profiles were obtained from Gene Expression Omnibus (GEO) datasets. The differentially expressed RNAs were identified using R software and the competing endogenous RNA (ceRNA) network was constructed using Cytoscape. Functional and pathway enrichment analyses were performed to identify the candidate circRNA-mediated aberrant signaling pathways. The hub genes were identified by MCODE and CytoHubba plugins of Cytoscape, and then a subnetwork regulatory module was established. Results A total of 27 circRNA-miRNA pairs and 208 miRNA-mRNA pairs, including 12 circRNAs, 24 miRNAs and 112 mRNAs were included in the ceRNA network. Subsequently, a subnetwork, including 4 circRNAs, 5 miRNAs and 6 mRNAs, was established based on related circRNA-miRNA-mRNA regulatory modules. Conclusions In summary, this work analyzes the characteristics of circRNA as competing endogenous RNA in AML pathogenesis, which would provide hints for developing novel prognostic, diagnostic and therapeutic strategy for AML.


Diagnostics ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 829
Author(s):  
Yana Kogan ◽  
Edmond Sabo ◽  
Majed Odeh

Objectives: The role of serum C-reactive protein (CRPs) and pleural fluid CRP (CRPpf) in discriminating uncomplicated parapneumonic effusion (UCPPE) from complicated parapneumonic effusion (CPPE) is yet to be validated since most of the previous studies were on small cohorts and with variable results. The role of CRPs and CRPpf gradient (CRPg) and of their ratio (CRPr) in this discrimination has not been previously reported. The study aims to assess the diagnostic efficacy of CRPs, CRPpf, CRPr, and CRPg in discriminating UCPPE from CPPE in a relatively large cohort. Methods: The study population included 146 patients with PPE, 86 with UCPPE and 60 with CPPE. Levels of CRPs and CRPpf were measured, and the CRPg and CRPr were calculated. The values are presented as mean ± SD. Results: Mean levels of CRPs, CRPpf, CRPg, and CRPr of the UCPPE group were 145.3 ± 67.6 mg/L, 58.5 ± 38.5 mg/L, 86.8 ± 37.3 mg/L, and 0.39 ± 0.11, respectively, and for the CPPE group were 302.2 ± 75.6 mg/L, 112 ± 65 mg/L, 188.3 ± 62.3 mg/L, and 0.36 ± 0.19, respectively. Levels of CRPs, CRPpf, and CRPg were significantly higher in the CPPE than in the UCPPE group (p < 0.0001). No significant difference was found between the two groups for levels of CRPr (p = 0.26). The best cut-off value calculated by the receiver operating characteristic (ROC) analysis for discriminating UCPPE from CPPE was for CRPs, 211.5 mg/L with area under the curve (AUC) = 94% and p < 0.0001, for CRPpf, 90.5 mg/L with AUC = 76.3% and p < 0.0001, and for CRPg, 142 mg/L with AUC = 91% and p < 0.0001. Conclusions: CRPs, CRPpf, and CRPg are strong markers for discrimination between UCPPE and CPPE, while CRPr has no role in this discrimination.


2019 ◽  
Vol 51 (2) ◽  
pp. 51-58 ◽  
Author(s):  
Yun-yan Lou ◽  
Qiong-dan Wang ◽  
Yu-tian Lu ◽  
Meng-yun Tu ◽  
Xi Xu ◽  
...  

Human cytomegalovirus (HCMV) is an opportunistic prototypic beta-herpesvirus that can cause severe and even fatal diseases in immune-naive newborns and immunocompromised adults. Host-virus interactions occurring at the transcriptional and posttranscriptional levels are critical for establishing an HCMV latent or lytic infection, but the mechanisms remain poorly understood. Herein, we investigated the expression of circRNAs in human leukemia monocytes (THP-1 cells) latently infected with HCMV and explored the diagnostic value of circRNAs in children with HCMV infection. A total of 2,110 and 1,912 circRNAs were identified in mock-infected and HCMV latent-infected THP-1 cells, respectively. Of these, we identified 1,421 differently expressed circRNAs, of which 650 were upregulated and 771 were downregulated. The host genes corresponding to the differentially expressed circRNAs were mainly involved in the regulation of host cell secretion pathways, cell cycle, and cell apoptosis. The differentially expressed circRNAs had binding sites for microRNAs, suggesting an important role in the mechanism of HCMV latent infection. Furthermore, a clinical analysis showed that the expression levels of hsa_circ_0001445 and hsa_circ_0001206 were statistically significantly different in HCMV-infected patients vs. normal controls, suggesting that these circRNAs could potentially serve as biomarkers of HCMV-infection.


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