Construction ceRNA network of regulated ferroptosis in doxorubicin induced myocardial injury
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ABSTRACT:
ORGANISM(S): Mus musculus Mus
PROVIDER: GSE207737 | GEO | 2023/01/03
REPOSITORIES: GEO
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Project description:Adiponectin (APN) is an endogenous adipokine secreted from adipocytes that exerts an anti-inflammation property. AdipoAI is an orally active adiponectin receptor agonist identified by our group, which can emulate APN's anti-inflammatory properties through mechanisms not fully understood. To explore AdipoAI function, we used lncRNA microarray and got differential lncRNA/mRNA expression medicated by AdipoAI. Identified as one kind of non-coding RNA with more than 200bp length, lncRNA has been demonstrated to have abundance biological functions, including anti-inflammatory response. In the current study, we performed an lncRNA microarray in LPS-induced Raw264.7 cells which pre-stimulated with AdipoAI, and screened 110 DElncRNAs and 190 DEmRNAs. Enrichment analyses were conducted to total mRNAs and DEmRNAs, including GSVA, ssGSEA, GO/KEGG, GSEA and PPI analysis. Among all these processes, endocytosis was significantly enriched. A co-expression analysis was built based on DElncRNAs and DEmRNAs. Then, using Targetscan and miRwalk to predict related microRNAs of DElncRNAs and DEmRNAs respectively, we established competing endogenous RNA (ceRNA) networks including 54 mRNAs from 8 GO items. Furthermore, 33 m6A methylation related marker genes were obtained from previous study and used for the construction of m6A related-lncRNA network using the co-expression analysis. We identified FTO as the hub gene of the network, and 14 lncRNAs that interacted with it. The expression levels of 10 lncRNAs selected from ceRNA and FTO- related lncRNAs networks were validated with qRT-PCR. Finally, Macrophage phenotype scores showed that AdipoAI could attenuate the M2b and M2c polarization of macrophage and correlate with the above lncRNAs. Our work reveals that lncRNA might involve in the anti-inflammation process of AdipoAI in LPS-induced macrophages through ceRNA network and epigenetic regulation of m6A. Mechanistically, these lncRNAs associated with AdipoAI might be related to endocytosis and polarization in macrophage, and provide new candidates for the anti-inflammatory application of APN and its receptor agonist.
2023-01-01 | GSE212065 | GEO
Project description:Construction of ceRNA network based on an RNA‑seq shows prognostic lncRNA biomarkers in Perthes’ disease
2023-05-15 | GSE217908 | GEO
Project description:Diffuse large B-cell lymphoma (DLBCL), the most common form of non-Hodgkin lymphoma, is characterized by an aggressive clinical course. In approximately one-third of DLBCL patients, first-line multi-agent immunochemotherapy fails to produce a durable response. Molecular heterogeneity and apoptosis resistance pose major therapeutic challenges in DLBCL treatment. To circumvent apoptosis resistance, the induction of ferroptosis might represent a promising strategy for lymphoma therapy. Here, a compound library targeting epigenetic modulators was screened to identify ferroptosis-sensitizing drugs. Strikingly, bromodomain and extra-terminal domain (BET) inhibitors sensitized cells of the germinal center B cell-like (GCB) subtype of DLBCL to ferroptosis induction and the combination of BET inhibitors with ferroptosis inducers, such as dimethyl fumarate (DMF) or RSL3, synergized in the killing of DLBCL cells in vitro and in vivo. On the molecular level, the BET protein BRD4 was found to be an essential regulator of ferroptosis suppressor protein 1 (FSP1) expression and to thus protect GCB DLBCL cells from ferroptosis. Collectively, we identified and characterized BRD4 as an important player in ferroptosis suppression in GCB DLBCL and provide a rationale for the combination of BET inhibitors with ferroptosis-inducing agents as a novel therapeutic approach for DLBCL treatment.
2023-08-01 | GSE231871 | GEO
Project description:The heart suffers from a severe loss of cardiomyocyte after myocardial infarction (MI). However, it is not known which type of cell death is the major contributor of the loss of cardiomyocytes. By studying a mouse heart MI model at a regenerative and a non-regenerative stage, we demonstrate that ferroptosis, not apoptosis or necroptosis, is the major contributor to cardiomyocyte death starting at 1 day-post-MI. Intrinsic Pitx2 signaling in cardiomyocyte prevents ferroptosis. Meanwhile, cardiac fibroblasts expressing high level of Fth1 interact with cardiomyocytes to share the iron burden, therefore inhibit cardiomyocyte ferroptosis. Cardiomyocyte Pitx2 also inhibits Tsp1 expression, therefore negatively regulate fibroblast-to-myofibroblast activation to limit fibrosis.
2023-06-02 | GSE211568 | GEO
Project description:Expression changes of competitive endogenous RNAs (ceRNAs) have been proposed to influence microRNA (miRNA) activity and thereby regulate other transcripts that contain miRNA binding sites. Here, we find that although miRNA levels define the extent of repression, they do not affect the magnitude of the ceRNA expression change required to observe derepression. Canonical 6-nt sites, which typically mediate modest repression, can nonetheless compete for miRNA binding, with potency ~20% of that observed for canonical 8-nt sites. Sites with extensive additional complementarity can be even more potent, but this occurs predominantly through miRNA degradation rather than competition. Cooperative binding of closely spaced sites for different miRNAs can also increase potency. These results provide quantitative insights into the stoichiometric relationship between miRNA and target abundance, target-site spacing and affinity requirements for ceRNA-mediated gene regulation and specify the unusual circumstances in which ceRNA-mediated gene regulation might be observed. Sixty-four mRNA profiles were generated of 1) primary hepatocytes of mice expressing variable levels of a recombinant Adenovirus expressing the transcript of AldolaseA (Ad-AldoA), containing sites matching miR-122, let-7, miR-192, miR-194 or a mutated site (no site) or 2) embryonic stem (ES) cells that were transfected with a Tet-inducible dual-color reporter construct expressing enhanced yellow fluorescent protein (eYFP) and mCherry that contains zero (0s) or three (3s) 8 nt miRNA seed matches for miR-293 or miR-92 in the 3� UTR. ES cells were sorted with a FACSAria IIIu flow cytometer into three bins based on their eYFP fluorescence intensity. All samples were sequenced in duplicates by an Illumina HiSeq 2500. Library preparation and sequencing were performed by Fasteris SA (Switzerland) or by the Functional Genomics Centre Zürich (FGCZ). Three small RNA profiles or either primary hepatocytes or embryonic stem cells were also generated by Solexa sequencing.
2016-10-27 | E-GEOD-76288 | biostudies-arrayexpress
Project description:Ferroptosis, a cell death pathway driven by lipid peroxidation, is implicated in several human diseases including cancer. Although ferroptosis is entwined with apoptosis, it currently has no characteristic biomarkers or gene signature. In this project we established a continuous phenotypic gradient between ferroptosis and apoptosis and coupled it to transcriptomic and metabolomic landscapes. Omics and mechanistic studies revealed that ferroptosis was associated with enhanced MITF activity, lysosomal function, glutaminolysis, TCA cycle, and activation of ATF4, while its transition into apoptosis was attributed to enhanced ER-stress, ATF4/CHOP switch and PE/PC metabolic shift. The gradual ferroptosis-to-apoptosis transcriptomic landscape was used to generate a unique, unbiased transcriptomic predictor, the Gradient Gene Set (GGS), which classified ferroptosis and apoptosis with high accuracy. Further GGS optimization and datasets analysis of various ferroptotic and apoptotic responses revealed highly specific ferroptosis biomarkers, which were robustly validated in vitro and in vivo. A subset of the GGS was correlated with poor prognosis in breast cancer patients and in PDX models and was found to consist of different ferroptosis repressors, including PDAP1, whose knockdown suppressed breast tumor growth in a mouse model. Collectively, this study highlights molecular switches between ferroptosis and apoptosis, uncovering a highly prognostic predictive ferroptosis gene signature, pointing to a few ferroptosis repressors for targeted breast cancer therapy.
2024-03-07 | GSE235201 | GEO
Project description:Background: The growth and development of leaf and petiole have an important influence on the photosynthesis of plants. The research on molecular mechanism of leaf and petiole development is of great significance, whether it is to improve plant photosynthetic efficiency, cultivate varieties with high photosynthetic efficiency, or improve the yield of crops using leaves as food organs. In this study, we aimed to identify the mRNAs, long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs) related to leaf and petiole development in Chinese cabbage (Brassica campestris L. ssp. pekinensis). These data were then used to construct competitive endogenous RNA (ceRNA) networks, which can provide valuable information for better understanding the mechanism of leaf and petiole development. Results: In this study, the leaf and petiole of the baby Chinese cabbage inbred line ‘PHL’ were used as research materials for whole-transcriptome sequencing. A total of 10646 differentially expressed (DE) mRNAs, 303 DE lncRNAs, 7 DE circRNAs, and 195 DE miRNAs were identified between the leaf and petiole. Some transcription factors or proteins that play important roles in leaf and petiole development were identified, such as xyloglucan endotransglucosylase/hydrolase (XTH) protein, expansion protein, TCP15 transcription factor, bHLH transcription factor, LOB domain protein, cellulose synthase (CESA), MOR1-like protein, and plant hormone biosynthesis related genes. Additionally, we constructed a leaf and petiole development-related ceRNA regulatory network, and obtained 85 pairs of ceRNA relationships, including 71 DEmiRNA-DEmRNA, 12 DEmiRNA-DElncRNA and 2 DEmiRNA-DEcircRNA. Three LSH genes (BrLSH1, BrLSH2 and BrLSH3) with significant differential expression between leaf and petiole of baby Chinese cabbage were screened from transcriptome data for subcellular localization analysis and overexpression transgenic verification. The results showed that BrLSH1, BrLSH2 and BrLSH3 were nucleoprotein and BrLSH2 has an obvious inhibitory effect on the growth and development of Arabidopsis thaliana. Conclusions: Our results revealed the potential mRNAs and non-coding RNAs (ncRNAs) involved in leaf and petiole development, which laid a foundation for further research on the molecular mechanism of leaf and petiole development in Chinese cabbage.
2022-12-29 | GSE218959 | GEO
Project description:Purpose: We aimed to detected the circRNA expression profile and constructed a circRNA-based competing endogenous RNA (ceRNA) network in autism. Methods:Valproate acid was used to establish an in vivo model of autism in mice. circRNAs in autism group was identified by RNA sequencing. The expression of circRNAs were detected by real-time PCR. Module analysis was conducted followed by GO and KEGG pathway enrichment analysis. Results: A total of 1059 differentially expressed circRNAs (477 upregulated and 582 downregulated) in autism group. The expression of novel_circ_015779 and novel_circ_035247 were detected by real-time PCR. A ceRNA network based on altered circRNAs was established, with 9715 nodes and 150408 edges. The top three modules were all correlated with autism-related pathways involving ‘TGF-beta signaling pathway’, ‘Notch signaling pathway’, ‘MAPK signaling pathway’, ‘long term depression’, ‘thyroid hormone signaling pathway’, etc. Conclusions: The present study reveals a novel circRNA involved mechanisms in the pathogenesis of autism.
2020-12-29 | GSE163904 | 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 | 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