Identification and Analysis of Dysregulated lncRNA, microRNA and mRNA expression profiles and construction of ceRNA network in THP-1 macrophage infected with Talaromyces marneffei
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE154780 | GEO | 2020/12/01
REPOSITORIES: GEO
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Project description:BackgroundCompetitive 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.MethodsNext-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.ResultsIn 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.ConclusionsThe 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.
| S-EPMC7811284 | biostudies-literature
Project description:BACKGROUND: Competitive endogenous RNA (ceRNA) reveals new mechanisms for interactions between RNAs. However, knowledge of ceRNA regulatory networks in macrophages infected with Talaromyces marneffei (T. marneffei, TM) is still limited. This study aims to explore the expression profiles of lncRNA, miRNA and mRNA, and the changes of ceRNA network related to immunity, inflammation, metabolism in TM-infected macrophage. METHODS: Next-generation sequencing technology (NGS) was used to obtain mRNA, miRNA and lncRNA expression profiles in TM-infected macrophages and normal macrophages. Cuffdiff and DESeq2 software packages are used to identify differentially expressed lncRNA, miRNA and mRNA. The function enrichment analysis was performed by GOseq package in R platform, and the lncRNA–miRNA–mRNA interaction ceRNA network was established in Cytoscape. Functional enrichment analysis was performed on genes contained in the ceRNA network, and genes significantly enriched in functional pathways were selected for qRT-PCR verification. RESULTS: A total of 119 lncRNAs, 28 miRNAs and 208 mRNAs were identified as differentially expressed RNAs in TM-infected macrophages. Among them, 38 lncRNAs, 10 miRNAs and 109 mRNAs are contained in the ceRNA regulatory network. GO analysis and KEGG pathway of mRNA in the ceRNA network showed that macrophages infected with TM activated pathways and functions related to immune response, metabolic response and inflammatory response. Select genes that are significantly abundant in GO analysis and KEGG pathway. The core genes were selected for quantitative real-time PCR (qRT-PCR) to verify consistency with the sequencing results. Eight groups of ceRNAs consisting of 3 mRNAs, 5 lncRNAs, and 2 miRNAs were verified. They are mRNA CSF3, IL24, LIF. lncRNA IL6R-AS1, LINC02009, AC068831.1, AC006252.1, LINC02466. These genes may be involved in immune response and inflammatory response-related pathways and functions in TM-infected macrophages. CONCLUSIONS: The CeRNA network plays an important role in understanding the mechanism of TM infection in macrophages. This study may provide effective and novel insights for further understanding the underlying mechanism of Talaromyces marneffei.
2020-12-01 | GSE154779 | GEO
Project description:BACKGROUND: Competitive endogenous RNA (ceRNA) reveals new mechanisms for interactions between RNAs. However, knowledge of ceRNA regulatory networks in macrophages infected with Talaromyces marneffei (T. marneffei, TM) is still limited. This study aims to explore the expression profiles of lncRNA, miRNA and mRNA, and the changes of ceRNA network related to immunity, inflammation, metabolism in TM-infected macrophage. METHODS: Next-generation sequencing technology (NGS) was used to obtain mRNA, miRNA and lncRNA expression profiles in TM-infected macrophages and normal macrophages. Cuffdiff and DESeq2 software packages are used to identify differentially expressed lncRNA, miRNA and mRNA. The function enrichment analysis was performed by GOseq package in R platform, and the lncRNA–miRNA–mRNA interaction ceRNA network was established in Cytoscape. Functional enrichment analysis was performed on genes contained in the ceRNA network, and genes significantly enriched in functional pathways were selected for qRT-PCR verification. RESULTS: A total of 119 lncRNAs, 28 miRNAs and 208 mRNAs were identified as differentially expressed RNAs in TM-infected macrophages. Among them, 38 lncRNAs, 10 miRNAs and 109 mRNAs are contained in the ceRNA regulatory network. GO analysis and KEGG pathway of mRNA in the ceRNA network showed that macrophages infected with TM activated pathways and functions related to immune response, metabolic response and inflammatory response. Select genes that are significantly abundant in GO analysis and KEGG pathway. The core genes were selected for quantitative real-time PCR (qRT-PCR) to verify consistency with the sequencing results. Eight groups of ceRNAs consisting of 3 mRNAs, 5 lncRNAs, and 2 miRNAs were verified. They are mRNA CSF3, IL24, LIF. lncRNA IL6R-AS1, LINC02009, AC068831.1, AC006252.1, LINC02466. These genes may be involved in immune response and inflammatory response-related pathways and functions in TM-infected macrophages. CONCLUSIONS: The CeRNA network plays an important role in understanding the mechanism of TM infection in macrophages. This study may provide effective and novel insights for further understanding the underlying mechanism of Talaromyces marneffei.
2020-12-01 | GSE154765 | GEO
Project description:Talaromyces (Penicillium) marneffei is an emerging opportunistic pathogen associated with HIV infection, particularly in Southeast Asia and southern China. The rapid uptake and killing of T. marneffei conidia by phagocytic cells along with the effective induction of an inflammatory response by the host is essential for disease control. T. marneffei produces a number of different laccases linked to fungal virulence. To understand the role of the various laccases in T. marneffei, laccase-encoding genes were investigated. Targeted single, double and triple gene deletions of laccases encoding lacA, lacB, and lacC showed no significant phenotypic effects suggesting redundancy of function. When a fourth laccase-encoding gene, pbrB, was deleted in the ?lacA ?lacB ?lacC background, the quadruple mutant displayed delayed conidiation and the conidia were more sensitive to H2O2, sodium dodecyl sulfate (SDS), and antifungal agents than wild-type and other transformants. Conidia of the quadruple mutant showed marked differences in their interaction with the human monocyte cell line, THP-1 such that phagocytosis was significantly higher when compared with the wild-type at one and 2 hours of incubation while the phagocytic index was significantly different from 15 to 120 minutes. In addition, killing of the quadruple mutant by THP-1 cells was more efficient at 2 and 4 hours of incubation. The levels of the proinflammatory cytokines TNF-?, IL-1? and IL-6 from THP-1 cells infected with the quadruple mutant were also significantly increased in comparison with wild-type. The results demonstrate that production of laccases by T. marneffei actually promotes the pathogen's resistance to innate host defenses.
| S-EPMC4991349 | biostudies-literature
Project description:Identification and Analysis of Dysregulated lncRNA, microRNA and mRNA expression profiles and construction of ceRNA network in THP-1 macrophage infected with Talaromyces marneffei
| PRJNA647412 | ENA
Project description:Identification and Analysis of Dysregulated lncRNA, microRNA and mRNA expression profiles and construction of ceRNA network in THP-1 macrophage infected with Talaromyces marneffei [miRNA-seq]
| PRJNA647397 | ENA
Project description:Identification and Analysis of Dysregulated lncRNA, microRNA and mRNA expression profiles and construction of ceRNA network in THP-1 macrophage infected with Talaromyces marneffei [RNA-seq]
| PRJNA647421 | ENA
Project description:It is increasing evidence that ceRNA activity of long non-coding RNAs (lncRNAs) played critical roles in both normal physiology and tumorigenesis. However, functional roles and regulatory mechanisms of lncRNAs as ceRNAs in pancreatic ductal adenocarcinoma (PDAC), and their potential implications for early diagnosis remain unclear. In this study, we performed a genome-wide analysis to investigate potential lncRNA-mediated ceRNA interplay based on "ceRNA hypothesis". A dysregulated lncRNA-associated ceRNA network (DLCN) was constructed by utilizing sample-matched miRNA, lncRNA and mRNA expression profiles in PDAC and normal samples in combination with miRNA regulatory network. The results of network analysis uncovered seven novel lncRNAs as functional ceRNAs whose aberrant expression will result in the extensive variation in tumorigenic or tumor-suppressive gene expression through DLCN at the post-transcriptional level contributing to PDAC. Therefore, we developed a 7-lncRNA signature (termed LncRisk-7) based on the expression data of seven lncRNAs and SVM algorithm as a novel diagnostic tool to improve early diagnosis of PDAC. The LncRisk-7 achieved high performance in distinguishing PDAC patients from nonmalignant pancreas samples in the discovery cohort and was further confirmed in another two independent validation cohorts. Functional analysis demonstrated that seven lncRNA biomarkers act as ceRNAs involving the regulation of cell death, cell adhesion and cell cycle. This study will help to improve our understanding of the lncRNA-mediated ceRNA regulatory mechanisms in the pathogenesis of PDAC and provide novel lncRNAs as candidate diagnostic biomarkers or potential therapeutic targets.
| S-EPMC5302921 | biostudies-literature
Project description:Talaromyces (Penicillium) marneffei is an important pathogenic thermally dimorphic fungus causing systemic mycosis in Southeast Asia. The clinical significance of T. marneffei became evident when the human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome epidemic arrived in Southeast Asia in 1988. Subsequently, a decline in the incidence of T. marneffei infection among HIV-infected patients was seen in regions with access to highly active antiretroviral therapy and other control measures for HIV. Since the 1990s, an increasing number of T. marneffei infections have been reported among non-HIV-infected patients with impaired cell-mediated immunity. Their comorbidities included primary adult-onset immunodeficiency due to anti-interferon-gamma autoantibodies and secondary immunosuppressive conditions including other autoimmune diseases, solid organ and hematopoietic stem cell transplantations, T-lymphocyte-depleting immunsuppressive drugs and novel anti-cancer targeted therapies such as anti-CD20 monoclonal antibodies and kinase inhibitors. Moreover, improved immunological diagnostics identified more primary immunodeficiency syndromes associated with T. marneffei infection in children. The higher case-fatality rate of T. marneffei infection in non-HIV-infected than HIV-infected patients might be related to delayed diagnosis due to the lack of clinical suspicion. Correction of the underlying immune defects and early use of antifungals are important treatment strategies. Clinicians should be familiar with the changing epidemiology and clinical management of T. marneffei infection among non-HIV-infected patients.
| S-EPMC4820671 | biostudies-other
Project description:Talaromyces marneffei (T. marneffei) immune escape is essential in the pathogenesis of talaromycosis. It is currently known that T. marneffei achieves immune escape through various strategies. However, the role of cellular alternative splicing (AS) in immune escape remains unclear. Here, we depict the AS landscape in macrophages upon T. marneffei infection via high-throughput RNA sequencing and detect a truncated protein of NCOR2 / SMRT, named NCOR2-013, which is significantly upregulated after T. marneffei infection. Mechanistic analysis indicates that NCOR2-013 forms a co-repression complex with TBL1XR1 / TBLR1 and HDAC3, thereby inhibiting JunB-mediated transcriptional activation of pro-inflammatory cytokines via the inhibition of histone acetylation. Furthermore, we identify TUT1 as the AS regulator that regulates NCOR2-013 production and promotes T. marneffei immune evasion. Collectively, these findings indicate that T. marneffei escapes macrophage killing through TUT1-mediated alternative splicing of NCOR2 / SMRT, providing insight into the molecular mechanisms of T. marneffei immune evasion and potential targets for talaromycosis therapy.
| S-EPMC10579421 | biostudies-literature