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 Circular RNA Associated Cerna Network Reveals Potential CircRNA Biomarkers in Human Breast Cancer

2020 ◽  
Author(s):  
Hui Shen ◽  
Huan Pan ◽  
Jianju Lu ◽  
Jianfen Shen ◽  
Longsheng Xu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Survival Analysis ◽  
Correlation Analysis ◽  
Mrna Expression ◽  
Circular Rna ◽  
Comprehensive Analysis ◽  
Differentially Expressed ◽  
Hub Genes ◽  
Cerna Network ◽  
Competitive Endogenous Rna

Abstract BackgroundThere is increasing evidence that circular RNA (circRNA) is closely related to tumorigenesis and cancer progression. circRNA has been identified as a sponge of microRNA (miRNA) in a competitive endogenous RNA (ceRNA) network and is involved in the regulation of mRNA expression. However, the roles of cancer specific circRNAs in circRNA-related ceRNA network of breast cancer (BRCA) are still unclear. This study aims to construct a ceRNA network associated with circRNA and to explore new therapeutic and prognostic targets and biomarkers for breast cancer.MethodsWe 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, these data were included in the study for comprehensive analysis. 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 analysis 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. The STRING search tool was used to predict the interaction between proteins, and the hub genes were screened by the MCODE plugin in Cytoscape.ResultsA 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 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 a total of 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. After comprehensive analysis, four potential ceRNA regulatory axes were constructed based on three circRNAs, two miRNAs, and three mRNAs.ConclusionsThis study provides an effective bioinformatics basis for further understanding 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 lncRNA-miRNA-mRNA ceRNA Network in Human Diarrhea Irritable Bowel Syndrome

2021 ◽  
Author(s):  
Jun-wei LIANG ◽  
Wen-jun BAI ◽  
Xiao-yan WANG ◽  
Li-li CHI
Keyword(s):  
Irritable Bowel Syndrome ◽  
Molecular Mechanisms ◽  
Enrichment Analysis ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Integrated Analysis ◽  
Down Regulation ◽  
Tissue Samples ◽  
Cerna Network ◽  
Irritable Bowel

Abstract Background:Many studies on long chain non-coding RNAs (lncRNAs) are published in recent years. But the roles of lncRNAs in diarrhea irritable bowel syndrome (IBS-D) are still unclear and should be further examined. The present work focused on determining the molecular mechanisms underlying lncRNAs regulation in IBS-D on the basis of the lncRNA-miRNA-mRNA competing endogenous RNA (ceRNA) network.Methods:This study collected the mRNAs (GSE36701) expression data within human tissue samples with IBS-D group and normal group based on Gene Expression Omnibus (GEO) database and collected the differentially expressed lncRNAs (DELs) and differentially expressed miRNAs (DEmiRs) based on PubMed.Functional enrichment analysis of DEGs was performed on the DAVID database. Then the interaction network was constructed and visualized using STRING database and Cytoscape.Results: This study identified 3192 DEmRNAs (1437 with up-regulation and 1755 with down-regulation),29 DEmiRs (18 upregulated and 11 downregulated)and 2 DELs(one upregulated and one downregulated) between IBS-D and control samples.Furthermore,we constructed a lncRNA-miRNA-mRNA network through two DELs (lncRNA TUG1 with up-regulation and lncRNA H19 with down-regulation), four DemiRs (hsa-miR-148a-3p,hsa-miR-342-3p,hsa-miR-149-5p with up-regulation and hsa-miR-219a-5p with down-regulation)and 24 DEGs (4 with up-regulation and 20 with down-regulation) with 42 axes. Simultaneously, we conducted functional enrichment and pathway analyses on genes within the as-constructed ceRNA network. According to our PPI/ceRNA network and functional enrichment analysis results, two critical genes were found (BCL2L11 and QKI). Conclusion:In conclusion, the ceRNA interaction axis we identified is a potentially critical target for treating IBS-D.BCL2L11 axis(LncH19-hsa-miR-148a-3p-BCL2L11) may via interaction with PI3K/AKT pathways in IBS-D.Our results shed more lights on the possible pathogenic mechanism in IBS-D using a lncRNA-associated ceRNA network.

scholarly journals Investigation of Candidate Genes and Pathways in Basal/TNBC Patients by Integrated Analysis

2021 ◽  
Vol 20 ◽  
pp. 153303382110195
Author(s):  
Qi Liu ◽  
Xiang Song ◽  
Zhaoyun Liu ◽  
Zhiyong Yu
Keyword(s):  
Breast Cancer ◽  
Survival Analysis ◽  
Differentially Expressed Genes ◽  
Molecular Mechanisms ◽  
Triple Negative ◽  
Differentially Expressed ◽  
Breast Cancer Cell Lines ◽  
Integrated Analysis ◽  
Transcription Activator ◽  
Luminal Type

Purpose: This study aims to identify the key pathway and related genes and to further explore the potential molecular mechanisms of triple negative breast cancer (TNBC). Methods: The transcriptome data and clinical information of breast cancer patients were downloaded from the TCGA database, including 94 cases of paracancerous tissue, 225 cases of Basal like type, 151 cases of Her2 type, 318 cases of Luminal type A, 281 cases of Luminal type B, and 89 cases of Normal Like type. The differentially expressed genes (DEGs) were identified based on the criteria of |logFC|≥1.5 and adjust P < 0.001.Their functions were annotated by gene ontology (GO) analysis and Kyoto Encyclopedia of differentially expressed genes & Genomes (KEGG) pathway analysis. Cox regression univariate analysis and Kaplan-Meier survival curves (Log-rank method) were used for survival analysis. FOXD1, DLL3 and LY6D were silenced in breast cancer cell lines, and cell viability was assessed by CCK-8 assay. Further, the expression of FOXD1, DLL3 and LY6D were explored by immunohistochemistry on triple negative breast tumor tissue and normal breast tissue. Results: A total of 533 DEGs were identified. Functional annotation showed that DEGs were significantly enriched in intermediate filament cytoskeleton, DNA−binding transcription activator activity, epidermis development, and Neuroactive ligand−receptor interaction. Survival analysis found that FOXD1, DLL3, and LY6D showed significant correlation with the prognosis of patients with the Basal-like type ( P < 0.05). CCK-8 assay showed that compared with Doxorubicin alone group, the cytotoxicity of Doxorubicin combined with siRNA-knockdown of FOXD1, DLL3, or LY6D was much significant. Conclusion: The DEGs and their enriched functions and pathways identified in this study contribute to the understanding of the molecular mechanisms of TNBC. In addition, FOXD1, DLL3, and LY6D may be defined as the prognostic markers and potential therapeutic targets for TNBC patients.

scholarly journals Integrated analysis of lncRNA-miRNA-mRNA ceRNA network in human aortic dissection

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Hao Zhang ◽  
Ce Bian ◽  
Simei Tu ◽  
Fanxing Yin ◽  
Panpan Guo ◽  
...  
Keyword(s):  
Aortic Dissection ◽  
Molecular Mechanisms ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Integrated Analysis ◽  
Down Regulation ◽  
Tissue Samples ◽  
Cerna Network

Abstract Background Many studies on long chain non-coding RNAs (lncRNAs) are published in recent years. But the roles of lncRNAs in aortic dissection (AD) are still unclear and should be further examined. The present work focused on determining the molecular mechanisms underlying lncRNAs regulation in aortic dissection on the basis of the lncRNA-miRNA-mRNA competing endogenous RNA (ceRNA) network. Methods This study collected the lncRNAs (GSE52093), mRNAs (GSE52093) and miRNAs (GSE92427) expression data within human tissue samples with aortic dissection group and normal group based on Gene Expression Omnibus (GEO) database. Results This study identified three differentially expressed lncRNAs (DELs), 19 differentially expressed miRNAs (DEmiRs) and 1046 differentially expressed mRNAs (DEGs) identified regarding aortic dissection. Furthermore, we constructed a lncRNA-miRNA-mRNA network through three lncRNAs (including two with up-regulation and one with down-regulation), five miRNAs (five with up-regulation), as well as 211 mRNAs (including 103 with up-regulation and 108 with down-regulation). Simultaneously, we conducted functional enrichment and pathway analyses on genes within the as-constructed ceRNA network. According to our PPI/ceRNA network and functional enrichment analysis results, four critical genes were found (E2F2, IGF1R, BDNF and PPP2R1B). In addition, E2F2 level was possibly modulated via lncRNA FAM87A-hsa-miR-31-5p/hsa-miR-7-5p or lncRNA C9orf106-hsa-miR-7-5p. The expression of IGF1R may be regulated by lncRNA FAM87A-hsa-miR-16-5p/hsa-miR-7-5p or lncRNA C9orf106-hsa-miR-7-5p. Conclusion In conclusion, the ceRNA interaction axis we identified is a potentially critical target for treating AD. Our results shed more lights on the possible pathogenic mechanism in AD using a lncRNA-associated ceRNA network.

scholarly journals Genomic Expression Profiling of Colorectal Cancer in Silico

2021 ◽  
Author(s):  
Feifei Liu ◽  
Yu Wang ◽  
Wenxue Li ◽  
Diancheng Li ◽  
Yuwei Xin ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Survival Analysis ◽  
Mrna Expression ◽  
Differentially Expressed Genes ◽  
Expression Profiles ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Analysis Tool ◽  
Hub Genes ◽  
Normal Tissues

Abstract Background: Colorectal cancer (CRC) is one of the most common malignancies of the digestive system; the progression and prognosis of which are affected by a complicated network of genes and pathways. The aim of this study was to identify potential hub genes associated with the progression and prognosis of colorectal cancer (CRC).Methods: We obtained gene expression profiles from GEO database to search differentially expressed genes (DEGs) between CRC tissues and normal tissue. Subsequently, we conducted a functional enrichment analysis, generated a protein–protein interaction (PPI) network to identify the hub genes, and analyzed the expression validation of the hub genes. Kaplan–Meier plotter survival analysis tool was performed to evaluate the prognostic value of hub genes expression in CRC patients.Results: A total of 370 samples, involving CRC and normal tissues were enrolled in this article. 283 differentially expressed genes (DEGs), including 62 upregulated genes and 221 downregulated genes between CRC and normal tissues were selected. We finally filtered out 6 hub genes, including INSL5, MTIM, GCG, SPP1, HSD11B2, and MAOB. In the database of TCGA-COAD, the mRNA expression of INSL5, MT1M, HSD11B2, MAOB in tumor is lower than that in normal; the mRNA expression of SPP1 in tumor is higher than that in normal. In the HPA database, the expression of INSL5, GCG, HSD11B2, MAOB in tumor is lower than that in normal tissues; the expression of SPP1 in the tumor is higher than that in normal tissues. Survival analysis revealed that INSL5, GCG, SPP1 and MT1M may serve as prognostic biomarkers in CRC. Conclusions: We screened out six hub genes to predict the occurrence and prognosis of patients with CRC using bioinformatics methods, which may provide new targets and ideas for diagnosis, prognosis and individualized treatment for CRC.

scholarly journals Integrative transcriptome data mining for identification of core lncRNAs in breast cancer

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7821 ◽  
Author(s):  
Xiaoming Zhang ◽  
Jing Zhuang ◽  
Lijuan Liu ◽  
Zhengguo He ◽  
Cun Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Prognostic Value ◽  
Early Stage ◽  
Expression Profiles ◽  
Diagnostic Value ◽  
The Cancer Genome Atlas ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Data Set

Background Cumulative evidence suggests that long non-coding RNAs (lncRNAs) play an important role in tumorigenesis. This study aims to identify lncRNAs that can serve as new biomarkers for breast cancer diagnosis or screening. Methods First, the linear fitting method was used to identify differentially expressed genes from the breast cancer RNA expression profiles in The Cancer Genome Atlas (TCGA). Next, the diagnostic value of all differentially expressed lncRNAs was evaluated using a receiver operating characteristic (ROC) curve. Then, the top ten lncRNAs with the highest diagnostic value were selected as core genes for clinical characteristics and prognosis analysis. Furthermore, core lncRNA-mRNA co-expression networks based on weighted gene co-expression network analysis (WGCNA) were constructed, and functional enrichment analysis was performed using the Database for Annotation, Visualization and Integrated Discovery (DAVID). The differential expression level and diagnostic value of core lncRNAs were further evaluated by using independent data set from Gene Expression Omnibus (GEO). Finally, the expression status and prognostic value of core lncRNAs in various tumors were analyzed based on Gene Expression Profiling Interactive Analysis (GEPIA). Results Seven core lncRNAs (LINC00478, PGM5-AS1, AL035610.1, MIR143HG, RP11-175K6.1, AC005550.4, and MIR497HG) have good single-factor diagnostic value for breast cancer. AC093850.2 has a prognostic value for breast cancer. AC005550.4 and MIR497HG can better distinguish breast cancer patients in early-stage from the advanced-stage. Low expression of MAGI2-AS3, LINC00478, AL035610.1, MIR143HG, and MIR145 may be associated with lymph node metastasis in breast cancer. Conclusion Our study provides candidate biomarkers for the diagnosis and prognosis of breast cancer, as well as a bioinformatics basis for the further elucidation of the molecular pathological mechanism of breast cancer.

scholarly journals Identification of a prognostic long non-coding RNA signature in breast cancer

2020 ◽  
Author(s):  
Gaochen Lan ◽  
Xiaoling Yu ◽  
Yanna Zhao ◽  
Jinjian Lan ◽  
Wan Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cox Regression ◽  
Prognostic Biomarker ◽  
Expression Profiles ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Cox Regression Analysis

Abstract Background: Breast cancer is the most common malignant disease among women. At present, more and more attention has been paid to long non-coding RNAs (lncRNAs) in the field of breast cancer research. We aimed to investigate the expression profiles of lncRNAs and construct a prognostic lncRNA for predicting the overall survival (OS) of breast cancer.Methods: The expression profiles of lncRNAs and clinical data with breast cancer were obtained from The Cancer Genome Atlas (TCGA). Differentially expressed lncRNAs were screened out by R package (limma). The survival probability was estimated by the Kaplan‑Meier Test. The Cox Regression Model was performed for univariate and multivariate analysis. The risk score (RS) was established on the basis of the lncRNAs’ expression level (exp) multiplied regression coefficient (β) from the multivariate cox regression analysis with the following formula: RS=exp a1 * β a1 + exp a2 * β a2 +……+ exp an * β an. Functional enrichment analysis was performed by Metascape.Results: A total of 3404 differentially expressed lncRNAs were identified. Among them, CYTOR, MIR4458HG and MAPT-AS1 were significantly associated with the survival of breast cancer. Finally, The RS could predict OS of breast cancer (RS=exp CYTOR * β CYTOR + exp MIR4458HG * β MIR4458HG + exp MAPT-AS1 * β MAPT-AS1). Moreover, it was confirmed that the three-lncRNA signature could be an independent prognostic biomarker for breast cancer (HR=3.040, P=0.000).Conclusions: This study established a three-lncRNA signature, which might be a novel prognostic biomarker for breast cancer.

scholarly journals Identifcation of The Ferroptosis-Related Gene Signature In Placenta of Patients With Early-Onset Preeclampsia

2021 ◽  
Author(s):  
Nana Yang ◽  
Qianghua Wang ◽  
Biao Ding ◽  
Yinging Gong ◽  
Yue Wu ◽  
...  
Keyword(s):  
Iron Homeostasis ◽  
Molecular Mechanisms ◽  
Late Onset ◽  
Expression Profiles ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Ppi Network ◽  
Network Analyses

Abstract Background: The accumulation of ROS resulting from upregulated levels of oxidative stress is commonly implicated in preeclampsia (PE). Ferroptosis is a novel form of iron-dependent cell death instigated by lipid peroxidation likely plays important role in PE pathogenesis. This study aims to investigate expression profiles and functions of the ferroptosis-related genes (FRGs) in early- and late-onset preeclampsia.Methods: The gene expression data and clinical information were downloaded from GEO database. The “limma” R package was used for screening differentially expressed genes. GO(Gene Ontology), Kyoto Encyclopedia of Genes and Genomes(KEGG) and protein protein interaction (PPI) network analyses were conducted to investigate the bioinformatics functions and molecular interactions of significantly different FRGs. Quantitative real-time reverse transcriptase PCR was used to verify the expression of hub FRGs in PE.Results: A total number of 4,215 DEGs were identified between EOPE and preterm cases and 3,356 DEGs were found between EOPE and LOPE subtypes. 20 significantly different FRGs were identified in EOPE, while only 3 in LOPE. Functional enrichment analysis revealed that the differentially expressed FRGs was mainly involved in EOPE and enriched in hypoxia- and iron-related pathways, such as response to hypoxia, iron homeostasis and iron ion binding process. The PPI network analysis and verification by RT-qPCR resulted in the identification of the following six interesting FRGs: FTH1, HIF1A, FTL, IREB2, MAPK8 and PLIN2. Conclusions: EOPE and LOPE owned distinct underlying molecular mechanisms and ferroptosis may be mainly implicated in pathogenesis of EOPE. Further studies are necessary for deeper inquiry into placental ferroptosis and its role in the pathogenesis of EOPE.

scholarly journals Integrated analysis of sex-biased mRNA and miRNA expression profiles in the gonad of the discus fish (Symphysodon aequifasciatus)

2018 ◽  
Author(s):  
yuanshuai Fu ◽  
Zhe Xu ◽  
Zaizhong Chen ◽  
Bin Wen ◽  
Jianzhong Gao
Keyword(s):  
Molecular Mechanisms ◽  
Target Genes ◽  
High Efficiency ◽  
Expression Profiles ◽  
Gonad Development ◽  
Differentially Expressed ◽  
Cdna Libraries ◽  
Integrated Analysis ◽  
Illumina Hiseq ◽  
Differentially Expressed Mirnas

The discus fish (Symphysodon aequifasciatus) is an ornamental fish that is well-known around the world. Phenotype investigation indicated that there are no significant differences in appearance between males and females of the discus fish. To better understand the sexual development mechanisms and obtain a high efficiency sex identification method in the artificial reproduction process of the discus fish, we constructed six cDNA libraries from three adult testes and three adult ovaries, and perform RNA-sequencing for identifying sex-biased candidate genes, microRNA (miRNA), and metabolic pathway using the Illumina Hiseq 4000. A total of 50,082 non-redundant genes (unigenes) were identified, of which 18,570 unigenes were significantly overexpressed in testes, and 11,182 unigenes were significantly overexpressed in ovaries, and 8 differentially expressed unigenes were validated by quantitative Real-Time PCR (qPCR). A total of 551 miRNAs were identified, of which 47 miRNAs were differentially expressed between testes and ovaries, and 7 differentially expressed miRNAs and one non-differential miRNA were validated by qPCR. Twenty-four of these differentially expressed miRNAs and their 15 predicted target genes constituted 41 important miRNA-mRNA interaction pairs, which may be important candidates for sex-related miRNAs and sex-related genes in the discus fish. Some of vital sex-related metabolic pathways were also identified that may play key roles in regulating gonad development of the discus fish. These results can provide important insights to better understand molecular mechanisms for sexual dimorphism in gonads development.

scholarly journals Identification and analysis of lncRNA, microRNA and mRNA expression profiles and construction of ceRNA network in Talaromyces marneffei-infected THP-1 macrophage

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e10529
Author(s):  
Yueqi Li ◽  
Wudi Wei ◽  
Sanqi An ◽  
Junjun Jiang ◽  
Jinhao He ◽  
...  
Keyword(s):  
Regulatory Networks ◽  
Expression Profiles ◽  
Enrichment Analysis ◽  
R Package ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Next Generation Sequencing Technology ◽  
Talaromyces Marneffei ◽  
Kegg Analysis ◽  
Cerna Network

Background Competitive endogenous RNA (ceRNA) reveals new mechanisms for interactions between RNAs, which have been considered to play a significant role in pathogen-host innate immune response. However, knowledge of ceRNA regulatory networks in Talaromyces marneffei (TM)-macrophages is still limited. Methods Next-generation sequencing technology (NGS) was used to obtain mRNA, miRNA and lncRNA expression profiles in TM-infected macrophages. The R package DESeq2 was used to identify differentially expressed lncRNA, miRNA and mRNA. The R package GOseq was used for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and the ceRNA network of lncRNA–miRNA–mRNA interaction was constructed in Cytoscape. Similarly, functional enrichment analysis on mRNA in the ceRNA network. Finally, two mRNAs and four lncRNAs in the ceRNA network were randomly selected to verify the expression using qRT-PCR. Results In total, 119 lncRNAs, 28 miRNAs and 208 mRNAs were identified as differentially expressed RNAs in TM-infected macrophages. The constructed ceRNA network contains 38 lncRNAs, 10 miRNAs and 45 mRNAs. GO and KEGG analysis of mRNA in the ceRNA network indicated that activated pathways in TM-infected macrophages were related to immunity, inflammation and metabolism. The quantitative validation of the expression of four randomly selected differentially expressed lncRNAs, AC006252.1, AC090197.1, IL6R-AS1, LINC02009 and two mRNAs, CSF1, NR4A3 showed that the expression levels were consistent with those in the RNA-sequencing. Conclusions The ceRNA network related to immunity, inflammation and metabolism plays an important role in TM-macrophage interaction. This study may provide effective and novel insights for further understanding the underlying mechanism of TM infection.

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