scholarly journals An integrated analysis of the competing endogenous RNA network and co-expression network revealed seven hub long non-coding RNAs in osteoarthritis

2020 ◽  
Vol 9 (3) ◽  
pp. 90-98 ◽  
Author(s):  
Haitao Chen ◽  
Liaobin Chen
Keyword(s):  
Extracellular Matrix ◽  
Expression Profiles ◽  
Osteoclast Differentiation ◽  
Signalling Pathway ◽  
Differentially Expressed ◽  
Integrated Analysis ◽  
Knee Cartilage ◽  
Competing Endogenous Rna ◽  
Cerna Network ◽  
Non Coding Rnas

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.

Integrated analysis profiles of long non–coding RNAs reveal potential biomarkers across brain regions in post–traumatic stress disorder

2020 ◽  
Author(s):  
Yaoyao Bian ◽  
Lili Yang ◽  
Zhongli Wang ◽  
Wen Li ◽  
Qing Wang ◽  
...  
Keyword(s):  
Post Traumatic Stress Disorder ◽  
Traumatic Stress ◽  
Stress Disorder ◽  
Expression Profiles ◽  
Differentially Expressed ◽  
Integrated Analysis ◽  
Post Traumatic Stress ◽  
Post Traumatic ◽  
Non Coding Rnas ◽  
Potential Biomarkers

Abstract Background Post–traumatic stress disorder (PTSD) is characterized by impaired fear extinction, excessive anxiety and depression. However, underlying mechanisms, especially the function roles of long non–coding RNAs (lncRNAs) involved in PTSD is still unclear. We argued that the lncRNAs, co–expressed mRNAs, as well as the associated pathways, are altered and may thus serve as potential biomarkers and key pathways related to PTSD.Methods The gene expression profiles of GSE68077 was downloaded from the GEO database, and the differentially expressed lncRNAs and mRNAs were identified. Gene ontology (GO) and Kyto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analysis were performed. Subsequently, protein–protein interaction (PPI) network was analyzed, and module analysis of the differentially expressed mRNAs was performed with Cytoscape software. Finally, lncRNAs–mRNAs co–expression network was constructed and core pair lncRNAs involved in PTSD were mapped.Results A total of 45 differentially expressed lncRNAs and 726 differentially expressed mRNAs were obtained. Among of which, 17 lncRNAs and 86 mRNAs were inter–regulated, and most of the lncRNAs–mRNAs co–expression showed positive correlations. The lncRNAs–mRNAs co–expressed network suggested the potentially functional roles of lncRNAs, regulated mRNAs and related pathways in PTSD. By implication of the core pair network, lncRNA–NONMMUT010120.2 synergistically up–regulated Ppargc1a and down–regulated Cir1, Slc38a9, Atp6v0a2. Moreover, lncRNA–NONMMUT023440.2, NONMMUT034155.2, NONMMUT105407.1 and NONMMUT149972.1 were co–expressed with 10 co–expressed mRNAs, which indicated that lncRNAs involved in PTSD might work by regulating the co–expressed mRNAs.

scholarly journals Construction and Comprehensive Analysis of Dysregulated Long Noncoding RNA-Associated Competing Endogenous RNA Network in Moyamoya Disease

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Xuefeng Gu ◽  
Dongyang Jiang ◽  
Yue Yang ◽  
Peng Zhang ◽  
Guoqing Wan ◽  
...  
Keyword(s):  
Moyamoya Disease ◽  
Cerebral Artery ◽  
Regulatory Network ◽  
Noncoding Rna ◽  
Expression Profiles ◽  
Differentially Expressed ◽  
Competing Endogenous Rna ◽  
Cerna Network ◽  
And Control ◽  
Control Samples

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.

scholarly journals Comprehensive Analysis of the Expression Profiles of Long Non-Coding RNAs with Associated ceRNA Network Involved in the Colon Cancer Staging and Progression

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Meini Wu ◽  
Wenliang Li ◽  
Fengchang Huang ◽  
Jing Sun ◽  
Kang ping Li ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Expression Profiles ◽  
Comprehensive Analysis ◽  
Differentially Expressed ◽  
Stage Iii ◽  
Aberrant Expression ◽  
Normal Tissues ◽  
Cerna Network ◽  
Tumor Tissues ◽  
Non Coding Rnas

AbstractLong non-coding RNAs (lncRNAs) act as competing endogenous RNAs (ceRNAs) to compete with microRNAs (miRNAs) in cancer occurrence and development. However, the differential expression of RNAs and their ceRNA network during the development of colon cancer (CC) remains unclear. This study was aimed at comprehensive analysis of the lncRNAs and their ceRNA networks associated with CC. Whole transcriptome sequencing was performed on colorectal and adjacent normal tissues at different pathological stages. Forty-nine lncRNAs were differently expressed between the CC tissues and their adjacent normal tissues at all stages. Aberrant expression of lncRNA CDKN2B-AS1 and lncRNA MIR4435-2HG was confirmed by TCGA database. Moreover, 14 lncRNAs were differentially expressed between early and advance stages of the tumor tissues, and 117 miRNAs were specifically expressed in stage III & IV. Weighted gene co-expression network analysis of 17105 differently expressed mRNAs revealed that the mRNAs shown in module pink, midnight blue, black, and light cyan were related to TNM and pathological stage, and that these mRNAs were enriched in cancer related functions and pathways. As DElncRNA showed a trend of change similar to that of the DEmRNA and opposite to that of DEmiRNA, ceRNA network was constructed with 3 DEmiRNAs, 5 DElncRNAs, and 130 DEmRNAs. Real time PCR revealed that expression of MEG3 was decreased in the tumor tissues belonging to stage III and IV as compared to that in stage I. Moreover, hsa-miR-324-5p was upregulated, while FGFR3, PLCB4, and IKBKB were downregulated in the tumor tissues as compared to that in the adjacent normal tissues. Thus, this study revealed differentially expressed lncRNA between different stages of CC as well as suggested that lncRNA CDKN2B-AS1, MIR4435-2HG, and MEG3 may act as diagnostic biomarkers for the development of CC.

scholarly journals Integrated Analysis of LncRNA-mRNA Coexpression in the Extracellular Matrix of Developing Deciduous Teeth in Miniature Pigs

2019 ◽  
Vol 2019 ◽  
pp. 1-9
Author(s):  
Yang Li ◽  
Guoqing Li ◽  
Fu Wang ◽  
Xiaoshan Wu ◽  
Zhifang Wu ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Noncoding Rna ◽  
Tooth Development ◽  
Expression Profiles ◽  
Differentially Expressed ◽  
Deciduous Teeth ◽  
Human Tooth ◽  
Integrated Analysis ◽  
Miniature Pigs ◽  
Tooth Germs

Miniature pigs, a valuable alternative model for understanding human tooth development, have deciduous teeth from all four tooth families that are replaced once by permanent molars. The extracellular matrix (ECM) supports cells and maintains the integrity of tooth germs during tooth development. However, details on the role of the ECM in tooth development are poorly understood. Here, we performed long noncoding RNA (lncRNA) and messenger RNA (mRNA) expression profiles in the ECM components of deciduous tooth germs by RNA sequencing in miniature pigs. From the early cap to the late bell stages, we identified 4,562 and 3,238 differentially expressed genes (DEGs) from E40 to E50 and E50 to E60, respectively. In addition, a total of 1,464 differentially expressed lncRNAs from E40 to E50 and 969 differentially expressed lncRNAs from E50 to E60 were obtained. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that DEGs were enriched significantly for multiple signaling pathways, especially for the ECM pathway. We then outlined the detailed dynamic gene expression profiling of ECM components during deciduous molar development. Comparison of the cap and bell stages revealed that the structure and functions of the ECM dynamically changed. The ECM-related genes, including THBS1, COL4A5, COL4A6, COL1A1, CHAD, TNR, GP1BA, and ITGA3, were significantly changed, and some were shown to enrich during the bell stage development. Finally, we outlined the coexpression of lncRNAs and ECM properties during tooth development. We showed that the interplay of key lncRNAs could change ECM processes and influence the ECM establishment of tooth patterns to accomplish full tooth formation. These results might provide information to elucidate the regulation network of the lncRNA and ECM in tooth development.

scholarly journals Integrated analysis of differentially expressed genes and construction of a competing endogenous RNA network in human Huntington neural progenitor cells

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Xiaoping Tan ◽  
Yang Liu ◽  
Taiming Zhang ◽  
Shuyan Cong
Keyword(s):  
Transcription Factors ◽  
Progenitor Cells ◽  
Neural Progenitor Cells ◽  
Integrated Analysis ◽  
Ppi Network ◽  
Competing Endogenous Rna ◽  
Protein Coding ◽  
Protein Coding Genes ◽  
Cerna Network ◽  
Non Coding Rnas

Abstract Background Huntington's disease (HD) is one of the most common polyglutamine disorders, leading to progressive dyskinesia, cognitive impairment, and neuropsychological problems. Besides the dysregulation of many protein-coding genes in HD, previous studies have revealed a variety of non-coding RNAs that are also dysregulated in HD, including several long non-coding RNAs (lncRNAs). However, an integrated analysis of differentially expressed (DE) genes based on a competing endogenous RNA (ceRNA) network is still currently lacking. Methods In this study, we have systematically analyzed the gene expression profile data of neural progenitor cells (NPCs) derived from patients with HD and controls (healthy controls and the isogenic controls of HD patient cell lines corrected using a CRISPR-Cas9 approach at the HTT locus) to screen out DE mRNAs and DE lncRNAs and create a ceRNA network. To learn more about the possible functions of lncRNAs in the ceRNA regulatory network in HD, we conducted a functional analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) and established a protein–protein interaction (PPI) network for mRNAs interacting with these lncRNAs. Results We identified 490 DE mRNAs and 94 DE lncRNAs, respectively. Of these, 189 mRNAs and 20 lncRNAs were applied to create a ceRNA network. The results showed that the function of DE lncRNAs mainly correlated with transcriptional regulation as demonstrated by GO analysis. Also, KEGG enrichment analysis showed these lncRNAs were involved in tumor necrosis factor, calcium, Wnt, and NF-kappa B signaling pathways. Interestingly, the PPI network revealed that a variety of transcription factors in the ceRNA network interacted with each other, suggesting such lncRNAs may regulate transcription in HD by controlling the expression of such protein-coding genes, especially transcription factors. Conclusions Our research provides new clues for uncovering the mechanisms of lncRNAs in HD and can be used as the focus for further investigation.

scholarly journals Construction and Analysis of Competing Endogenous RNA Networks for Breast Cancer Based on TCGA Dataset

2020 ◽  
Vol 2020 ◽  
pp. 1-10 ◽  
Author(s):  
Xue Wang ◽  
Chundi Gao ◽  
Fubin Feng ◽  
Jing Zhuang ◽  
Lijuan Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Metastasis ◽  
Target Genes ◽  
Expression Profiles ◽  
The Cancer Genome Atlas ◽  
Differentially Expressed ◽  
Competing Endogenous Rna ◽  
Cerna Network ◽  
Competing Endogenous Rnas ◽  
Tcga Dataset

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.

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
Keyword(s):  
Expression Profiles ◽  
Area Under The Curve ◽  
Roc Curves ◽  
Diagnostic Value ◽  
Differentially Expressed ◽  
Competing Endogenous Rna ◽  
Diagnostic Efficacy ◽  
Go Analysis ◽  
Cerna Network ◽  
Neutrophil Degranulation

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.

scholarly journals Integrated Analysis of a Competing Endogenous RNA Network Reveals a Prognostic lncRNA Signature in Bladder Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Mou Peng ◽  
Xu Cheng ◽  
Wei Xiong ◽  
Lu Yi ◽  
Yinhuai Wang
Keyword(s):  
Bladder Cancer ◽  
Expression Patterns ◽  
Differential Expression Analysis ◽  
Differentially Expressed ◽  
Integrated Analysis ◽  
Competing Endogenous Rna ◽  
Predictive Tool ◽  
Aberrant Expression ◽  
Cerna Network ◽  
Rna Interaction

Long non-coding RNAs (lncRNAs) act as competing endogenous RNAs (ceRNAs) to regulate mRNA expression through sponging microRNA in tumorigenesis and progression. However, following the discovery of new RNA interaction, the differentially expressed RNAs and ceRNA regulatory network are required to update. Our study comprehensively analyzed the differentially expressed RNA and corresponding ceRNA network and thus constructed a potentially predictive tool for prognosis. “DESeq2” was used to perform differential expression analysis. Two hundred and six differentially expressed (DE) lncRNAs, 222 DE miRNAs, and 2,463 DE mRNAs were found in this study. The lncRNA-mRNA interactions in the miRcode database and the miRNA-mRNA interactions in the starBase, miRcode, and mirTarBase databases were searched, and a competing endogenous RNA (ceRNA) network with 186 nodes and 836 interactions was subsequently constructed. Aberrant expression patterns of lncRNA NR2F1-AS1 and lncRNA AC010168.2 were evaluated in two datasets (GSE89006, GSE31684), and real-time polymerase chain reaction was also performed to validate the expression pattern. Furthermore, we found that these two lncRNAs were independent prognostic biomarkers to generate a prognostic lncRNA signature by univariate and multivariate Cox analyses. According to the lncRNA signature, patients in the high-risk group were associated with a poor prognosis and validated by an external dataset. A novel genomic-clinicopathologic nomogram to improve prognosis prediction of bladder cancer was further plotted and calibrated. Our study deepens the understanding of the regulatory ceRNA network and provides an easy-to-do genomic-clinicopathological nomogram to predict the prognosis in patients with bladder cancer.

scholarly journals Integrated Analysis of Circular RNA-Associated ceRNA Network Reveals Potential circRNA Biomarkers in Human Breast Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-16
Author(s):  
Han Sheng ◽  
Huan Pan ◽  
Ming Yao ◽  
Longsheng Xu ◽  
Jianju Lu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Survival Analysis ◽  
Correlation Analysis ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Circular Rna ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Integrated Analysis ◽  
Cerna Network

Circular RNA (circRNA) is closely related to tumorigenesis and cancer progression. Yet, the roles of cancer-specific circRNAs in the circRNA-related ceRNA network of breast cancer (BRCA) remain unclear. The aim of this study was to construct a ceRNA network associated with circRNA and to explore new therapeutic and prognostic targets and biomarkers for breast cancer. We downloaded the circRNA expression profile of BRCA from Gene Expression Omnibus (GEO) microarray datasets and downloaded the miRNA and mRNA expression profiles of BRCA from The Cancer Genome Atlas (TCGA) database. Differentially expressed mRNAs (DEmRNAs), differentially expressed miRNAs (DEmiRNAs), and differentially expressed circRNAs (DEcircRNAs) were identified, and a competitive endogenous RNA (ceRNA) regulatory network was constructed based on circRNA–miRNA pairs and miRNA–mRNA pairs. Gene ontology and pathway enrichment analyses were performed on mRNAs regulated by circRNAs in ceRNA networks. Survival analysis and correlation analysis of all mRNAs and miRNAs in the ceRNA network were performed. A total of 72 DEcircRNAs, 158 DEmiRNAs, and 2762 DE mRNAs were identified. The constructed ceRNA network contains 60 circRNA–miRNA pairs and 140 miRNA–mRNA pairs, including 40 circRNAs, 30 miRNAs, and 100 mRNAs. Functional enrichment indicated that DEmRNAs regulated by DEcircRNAs in ceRNA networks were significantly enriched in the PI3K-Akt signaling pathway, microRNAs in cancer, and proteoglycans in cancer. Survival analysis and correlation analysis of all mRNAs and miRNAs in the ceRNA network showed that 13 mRNAs and 6 miRNAs were significantly associated with overall survival, and 48 miRNA–mRNA interaction pairs had a significant negative correlation. A PPI network was established, and 21 hub genes were determined from the network. This study provides an effective bioinformatics basis for further understanding of the molecular mechanisms and predictions of breast cancer. A better understanding of the circRNA-related ceRNA network in BRCA will help identify potential biomarkers for diagnosis and prognosis.

scholarly journals Integrated Analysis of Differentially Expressed Genes and Construction of a Competing Endogenous RNA Network in Human Huntington Neural Progenitor Cells

2020 ◽  
Author(s):  
Xiaoping Tan ◽  
Shuyan Cong ◽  
Yang Liu ◽  
Taiming Zhang
Keyword(s):  
Transcription Factors ◽  
Progenitor Cells ◽  
Neural Progenitor Cells ◽  
Integrated Analysis ◽  
Ppi Network ◽  
Competing Endogenous Rna ◽  
Protein Coding ◽  
Protein Coding Genes ◽  
Cerna Network ◽  
Non Coding Rnas

Abstract Background Huntington's disease (HD) is one of the most common polyglutamine disorders, leading to progressive dyskinesia, cognitive impairment, and neuropsychological problems. Besides the dysregulation of many protein-coding genes in HD, previous studies have revealed a variety of non-coding RNAs that are dysregulated in HD, including several long non-coding RNAs (lncRNAs). However, an integrated analysis of differentially expressed (DE) genes based on a competing endogenous RNA (ceRNA) network is still currently lacking. Results Here, we have systematically analyzed the gene expression profile data of neural progenitor cells (NPCs) derived from patients with HD and controls (healthy controls and the isogenic controls of HD patient cell lines corrected using CRISPR-Cas9 approach at the HTT locus, and we identified 490 DE mRNAs and 94 DE lncRNAs, respectively. Of these, 189 mRNAs and 20 lncRNAs were applied to create a ceRNA network. To learn more about the possible functions of lncRNAs in the ceRNA regulatory network in HD, we conducted a functional analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) and established a protein-protein interaction (PPI) network for mRNAs interacting with these lncRNAs. It is suggested that the function of DE lncRNAs mainly correlated with transcriptional regulation demonstrated by GO analysis. Also, KEGG enrichment analysis showed these lncRNAs were involved in tumor necrosis factor, calcium, Wnt, and NF-kappa B signaling pathways. Interestingly, the PPI network revealed that a variety of transcription factors in the ceRNA network interacted with each other, suggesting such lncRNAs may regulate transcription in HD by controlling the expression of such protein-coding genes, especially transcription factors. Conclusions Our research provides new clues for uncovering the mechanism of lncRNAs in HD and can be used as the focus for further investigation.

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