scholarly journals A Novel Competing Endogenous RNA Network Associated With the Pathogenesis of Graves’ Ophthalmopathy

2021 ◽  
Vol 12 ◽  
Author(s):  
Zifan Yue ◽  
Pei Mou ◽  
Sainan Chen ◽  
Fei Tong ◽  
Ruili Wei

Background: Growing evidence has recently revealed the characteristics of long noncoding (lncRNA)/circular RNA (circRNA)-microRNA (miRNA)-mRNA networks in numerous human diseases. However, a scientific lncRNA/circRNA-miRNA-mRNA network related to Graves’ ophthalmopathy (GO) remains lacking.Materials and methods: The expression levels of RNAs in GO patients were measured through high-throughput sequencing technology, and the results were proven by quantitative real-time PCR (qPCR). We constructed a protein-protein interaction (PPI) network using the Search Tool for the Retrieval of Interacting Genes (STRING) database and identified hub genes by the Cytoscape plug-in CytoHubba. Then, the miRNAs related to differentially expressed lncRNAs/circRNAs and mRNAs were predicted through seed sequence matching analysis. Correlation coefficient analysis was performed on the interesting RNAs to construct a novel competing endogenous RNA (ceRNA) network.Results: In total, 361 mRNAs, 355 circRNAs, and 242 lncRNAs were differentially expressed in GO patients compared with control patients, 166 pairs were identified, and ceRNA networks were constructed. The qPCR results showed that 4 mRNAs (THBS2, CHRM3, CXCL1, FPR2) and 2 lncRNAs (LINC01820:13, ENST00000499452) were differentially expressed between the GO patients and control patients.Conclusion: An innovative lncRNA/circRNA-miRNA-mRNA ceRNA network between GO patients and control patients was constructed, and two important ceRNA pathways were identified, the LINC01820:13-hsa-miR-27b-3p-FPR2 ceRNA pathway and the ENST00000499452-hsa-miR-27a-3p-CXCL1 pathway, which probably affect the autoimmune response and inflammation in GO patients.

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.


2019 ◽  
Vol 47 (8) ◽  
pp. 3580-3589 ◽  
Author(s):  
Yingyuan Li ◽  
Wulin Tan ◽  
Fang Ye ◽  
Faling Xue ◽  
Shaowei Gao ◽  
...  

Objective We aimed to explore potential microRNAs (miRNAs) and target genes related to atrial fibrillation (AF). Methods Data for microarrays GSE70887 and GSE68475, both of which include AF and control groups, were downloaded from the Gene Expression Omnibus database. Differentially expressed miRNAs between AF and control groups were identified within each microarray, and the intersection of these two sets was obtained. These miRNAs were mapped to target genes in the miRNet database. Functional annotation and enrichment analysis of these target genes was performed in the DAVID database. The protein-protein interaction (PPI) network from the STRING database and the miRNA-target-gene network were merged into a PPI-miRNA network using Cytoscape software. Modules of this network containing miRNAs were detected and further analyzed. Results Ten differentially expressed miRNAs and 1520 target genes were identified. Three PPI-miRNA modules were constructed, which contained miR-424, miR-15a, miR-542-3p, and miR-421 as well as their target genes, CDK1, CDK6, and CCND3. Conclusion The identified miRNAs and genes may be related to the pathogenesis of AF. Thus, they may be potential biomarkers for diagnosis and targets for treatment of AF.


2020 ◽  
Vol 34 ◽  
pp. 205873842097630
Author(s):  
Li Jiang ◽  
Mengmeng Zhang ◽  
Sixue Wang ◽  
Yuzhen Xiao ◽  
Jingni Wu ◽  
...  

The current study intended to explore the interaction of the long non-coding RNA (lncRNA), microRNA (miRNA), and messenger RNA (mRNA) under the background of competitive endogenous RNA (ceRNA) network in endometriosis (EMs). The differentially expressed miRNAs (DEmiRs), differentially expressed lncRNA (DELs), and differentially expressed genes (DEGs) between EMs ectopic (EC) and eutopic (EU) endometrium based on three RNA-sequencing datasets (GSE105765, GSE121406, and GSE105764) were identified, which were used for the construction of ceRNA network. Then, DEGs in the ceRNA network were performed with Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and protein-protein interaction (PPI) analysis. Besides, the DEmiRs in the ceRNA network were validated in GSE124010. And the target DELs and DEGs of verified DEmiRs were validated in GSE86534. The correlation of verified DEmiRs, DEGs, and DELs was explored. Moreover, gene set enrichment analysis (GSEA) was applied to investigate the function of verified DEmiRs, DEGs, and DELs. Overall, 1352 DEGs and 595 DELs from GSE105764, along with 27 overlapped DEmiRs between GSE105765 and GSE121406, were obtained. Subsequently, a ceRNA network, including 11 upregulated and 16 downregulated DEmiRs, 7 upregulated and 13 downregulated DELs, 48 upregulated and 46 downregulated DEGs, was constructed. The GO and KEGG pathway analysis showed that this ceRNA network probably was associated with inflammation-related pathways. Furthermore, hsa-miR-182-5p and its target DELs (LINC01018 and SMIM25) and DEGs (BNC2, CHL1, HMCN1, PRDM16) were successfully verified in the validation analysis. Besides, hsa-miR-182-5p was significantly negatively correlated with these target DELs and DEGs. The GSEA analysis implied that high expression of LINC01018, SMIM25, and CHL1, and low expression of hsa-miR-182-5p would activate inflammation-related pathways in endometriosis EU samples. LINC01018 and SMIM25 might sponge hsa-miR-182-5p to upregulate downstream genes such as CHL1 to promote the development of endometriosis.


2021 ◽  
Vol 2021 ◽  
pp. 1-21
Author(s):  
Jian-Yu Liu ◽  
Ying-Xiao Jiang ◽  
Meng-Yu Zhang ◽  
Chen Huo ◽  
Yi-Can Yang ◽  
...  

Background. Acute lung injury (ALI) is a fatal syndrome frequently induced by lipopolysaccharide (LPS) released from the bacterial cell wall. LPS could also trigger autophagy of lung bronchial epithelial cell to relieve the inflammation, while the overwhelming LPS would impair the balance of autophagy consequently inducing serious lung injury. Methods. We observed the autophagy variation of 16HBE, human bronchial epithelial cell, under exposure to different concentrations of LPS through western blot, immunofluorescence staining, and electron microscopy. Eight strands of 16HBE were divided into two groups upon 1000 ng/ml LPS stimulation or not, which were sent to be sequenced at whole transcriptome. Subsequently, we analyzed the sequencing data in functional enrichment, pathway analysis, and candidate gene selection and constructed a hsa-miR-663b-related competing endogenous RNA (ceRNA) network. Results. We set a series of concentrations of LPS to stimulate 16HBE and observed the variation of autophagy in related protein expression and autophagosome count. We found that the effective concentration of LPS was 1000 ng/ml at 12 hours of exposure and sequenced the 1000 ng/ml LPS-stimulated 16HBE. As a result, a total of 750 differentially expressed genes (DEGs), 449 differentially expressed lncRNAs (DElncRNAs), 76 differentially expressed circRNAs (DEcircRNAs), and 127 differentially expressed miRNAs (DEmiRNAs) were identified. We constructed the protein-protein interaction (PPI) network to visualize the interaction between DEGs and located 36 genes to comprehend the core discrepancy between LPS-stimulated 16HBE and the negative control group. In combined analysis of differentially expressed RNAs (DERNAs), we analyzed all the targeted relationships of ceRNA in DERNAs and figured hsa-miR-663b as a central mediator in the ceRNA network to play when LPS induced the variation of autophagy in 16HBE. Conclusion. Our research indicated that the hsa-miR-663b-related ceRNA network may contribute to the key regulatory mechanism in LPS-induced changes of autophagy and ALI.


2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Zhaojun Wang ◽  
Haifeng Li ◽  
Fajun Li ◽  
Xin Su ◽  
Junhang Zhang ◽  
...  

Background. Esophageal squamous cell carcinoma (ESCC) has a poor prognosis due to the lack of early disease symptoms. Using bioinformatics tools, this study aimed to discover differentially expressed nonprotein-coding RNAs and genes with potential prognostic relevance in ESCC. Methods. Two microRNAs (miRNAs) and one circular RNA (circRNA) microarray datasets were downloaded from the Gene Expression Omnibus (GEO) database. Differential expression of miRNAs (DEMs) and circRNAs (DECs) was, respectively, identified in ESCC tissue and compared to adjacent healthy tissue. Further analysis was performed using the miRNA microarray datasets, where miRTarBase was used to predict which messenger RNAs (mRNAs) was present. This was followed by protein-protein interaction (PPI) network, Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Ontology (GO) analyses. Moreover, cytoHubba and UALCAN were used to predict the important nodes and perform patient survival analysis, respectively. The miRNA-associated circRNAs were predicted using the ENCORI website. The interaction between DECs and the predicted circRNAs was also determined. A circRNA-miRNA-mRNA axis was constructed. Results. Associated with RAP1B and circ_0052867, two miRNAs (miR-133b and miR-139-5p) were identified as being differentially expressed and downregulated across the two datasets. Finally, the circ_0052867/miR-139-5p/RAP1B regulatory axis was established. Conclusion. This study provides support for the possible mechanisms of disease progression in ESCC.


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.


Hereditas ◽  
2021 ◽  
Vol 158 (1) ◽  
Author(s):  
Yucheng Fu ◽  
Qi Liu ◽  
Qiyuan Bao ◽  
Junxiang Wen ◽  
Zhuochao Liu ◽  
...  

Abstract Background Osteosarcoma is the primary bone malignant neoplasm that often develops metastasis. Increasing evidences have shown that non-coding RNAs (ncRNAs) relate to the progression of osteosarcoma. However, the ncRNAs’ roles in osteosarcoma metastasis are still unknown. Methods Differentially expressed (DE) RNAs were identified from Gene Expression Omnibus (GEO) database. Protein-protein interaction (PPI) of DE messenger RNAs (DEmRNAs) was built through STRING database. The target mRNAs and long ncRNAs (lncRNAs) of microRNAs (miRNA) were predicted through miRDB, Targetscan and Genecode databases, which then cross-checked with previously obtained DERNAs to construct competing endogenous RNA (ceRNA) network. All networks were visualized via Cytoscape and the hub RNAs were screened out through Cytoscape plug-in Cytohubba. The gene functional and pathway analyses were performed through DAVID and MirPath databases. The survival analyses of hub RNAs were obtained through Kaplan-Meier (KM) survival curves. Results Five hundred sixty-four DEmRNAs, 16 DElncRNAs and 22 DEmiRNAs were screened out. GO functional and KEGG pathway analyses showed that DERNAs were significantly associated with tumor metastasis. The ceRNA network including 6 lncRNAs, 55 mRNAs and 20 miRNAs were constructed and the top 10 hub RNAs were obtained. Above all, PI3K/AKT signaling pathway was identified as the most important osteosarcoma metastasis-associated pathway and its hub ceRNA module was constructed. The survival analyses showed that the RNAs in hub ceRNA module closely related to osteosarcoma patients’ prognosis. Conclusions The current study provided a new perspective on osteosarcoma metastasis. More importantly, the RNAs in hub ceRNA module might act as the novel therapeutic targets and prognostic factors for osteosarcoma patients.


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.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Taiyu Hui ◽  
Yuanyuan Zheng ◽  
Chang Yue ◽  
Yanru Wang ◽  
Zhixian Bai ◽  
...  

AbstractCompetitive endogenous RNA (ceRNA) is a transcript that can be mutually regulated at the post-transcriptional level by competing shared miRNAs. The ceRNA network connects the function of protein-encoded mRNA with the function of non-coding RNA, such as microRNA (miRNA), long non-coding RNA (lncRNA), and circular RNA (circRNA). However, compared with the ceRNA, the identification and combined analysis of lncRNAs, mRNAs, miRNAs, and circRNAs in the cashmere fineness have not been completed. Using RNA-seq technology, we first identified the miRNAs presented in Liaoning Cashmere Goat (LCG) skin, and then analyzed the mRNAs, lncRNAs, circRNAs expressed in LCG and Inner Mongolia cashmere goat (MCG) skin. As a result, 464 known and 45 new miRNAs were identified in LCG skin. In LCG and MCG skin, 1222 differentially expressed mRNAs were identified, 170 differentially expressed lncRNAs and 32 differentially expressed circRNAs were obtained. Then, qRT-PCR was used to confirm further the representative lncRNAs, mRNAs, circRNAs and miRNAs. In addition, miRanda predicted the relationships of ceRNA regulatory network among lncRNAs, circRNAs, miRNAs and mRNAs, the potential regulatory effects were investigated by Go and KEGG analysis. Through the screening and analysis of the results, the ceRNA network regulating cashmere fineness was constructed. LncRNA MSTRG14109.1 and circRNA452 were competed with miRNA-2330 to regulated the expression of TCHH, KRT35 and JUNB, which may provide a potential basis for further research on the process of regulating the cashmere fineness.


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.


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