Circ-Phkb promote LPS-induced acute lung injury via the TLR4/MyD88/NF-κB /CCL2 axis
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ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE226036 | GEO | 2024/02/07
REPOSITORIES: GEO
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Project description:Circ-Phkb promote LPS-induced acute lung injury via the TLR4/MyD88/NF-κB /CCL2 axis
| PRJNA938418 | ENA
Project description:BackgroundCircular RNAs (CircRNAs) have been associated with acute lung injury (ALI), but their molecular mechanisms remain unclear.MethodsThis study developed a rat model of lipopolysaccharide (LPS)-induced ALI and evaluated the modeling effect by hematoxylin and eosin staining, Masson's trichrome staining, lung wet-to-dry weight ratio, terminal deoxynucleotidyl transferase UTP nick end labeling (TUNEL), and enzyme-linked immunosorbent assay (ELISA) detection of inflammatory factors (interleukin-1β, tumor necrosis factor alpha, and interleukin-6). Using lung tissues from a rat model of LPS-induced ALI, we then conducted circRNA sequencing, mRNA sequencing, and bioinformatics analysis to obtain differential circRNA and mRNA expression profiles as well as potential ceRNA networks. Furthermore, we performed quantitative real-time polymerase chain reaction (qRT-PCR) assays to screen for circ-Phkb in ALI rat lung tissues, alveolar macrophages, and LPS-induced NR8383 cells. We conducted induction with or without LPS with circ-Phkb siRNA and overexpression lentivirus in NR8383. Cell Counting Kit-8, C5-Ethynyl-2'-deoxyuridine (Edu), TUNEL, and cytometry were used to identify proliferation and apoptosis, respectively. We detected inflammatory factors using ELISA. Finally, we used Western blot to detect the apoptosis-related proteins and TLR4/MyD88/NF-kB/CCL2 pathway activation.ResultsOur results revealed that both circRNA and mRNA profiles are different from those of the Sham group. We observed a significant circ-Phkb upregulation in NR8383 cells and LPS-exposed rats. Apoptosis and inflammation were greatly reduced when circ-Phkb expression was reduced in NR8383 cells, cell proliferation was increased, and circ-Phkb overexpression was decreased.ConclusionsIn terms of mechanism, circ-Phkb suppression inhibits CCL2 expression via the TLR4/MyD88/NF-kB pathway in LPS-induced alveolar macrophages.
| S-EPMC10826187 | biostudies-literature
Project description:Circular RNAs (circRNAs) represent a class of covalently closed RNAs, derived from a non-canonical splicing event, ubiquitously expressed among Eukaryotes and conserved among different species. We identified a circRNA (circ-ZNF609) involved in the regulation of human primary myoblast proliferation. Upon its depletion, the percentage of proliferating myoblasts was highly reduced. To deepen our knowledge about circ-ZNF609 role in cell cycle regulation, we studied its expression and function in Rhabdomyosarcoma (RMS), a pediatric skeletal muscle malignancy. We found that circ-ZNF609 is up-regulated in biopsies from both the two major RMS subtypes, the alveolar (ARMS) and the embryonal (ERMS), and we discovered that its knock-down blocks proliferation of an ERMS-derived cell line, while it has no effect on ARMS-derived cells. To understand the mechanism through which circ-ZNF609 affects cell proliferation we compared the different effects of circ-ZNF609 depletion in ERMS and ARMS and we identified genes and pathways on which the circRNA acts.
2018-12-14 | GSE117609 | GEO
Project description:This study shows that the TLR4/MyD88 pathway in intestinal mesenchymal cells promotes intestinal carcinogenesis in the APCmin mouse model.
2019-01-15 | GSE119341 | GEO
Project description:Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the digestive tract. The majority of GIST patients eventually develop resistance to imatinib therapy. To identify the responsible mechanisms, we investigated the differentially expressed mRNAs and circRNAs in imatinib-resistant GISTs using SBC ceRNA microarrays. We found that 107 mRNAs and 521 circRNAs were significantly differentially expressed between imatinib-naïve and imatinib-resistant GIST tissue samples. qRT-PCR analyses validated that circ-BRIP1, circ-EPHB4 and circ-RECQL4 and their host genes were upregulated in imatinib-resistant GISTs, and circ-BRIP1, circ-EPHB4, and RECQL4 were associated with imatinib resistance, tumor relapse and progression, and metastasis in GIST patients. The expression levels of circ-BRIP1, circ-EPHB4 and their host genes were also evaluated using TMAs with 150 human GISTs. The expression level of EPHB4 was significantly increased in high-grade GISTs in comparison to low-grade GISTs and correlated with imatinib resistance. Specifically, we first developed a method for high-throughput analysis of the expression of differentially expressed circRNAs by ISH-IHC in a set of FFPE-tissue microarrays in GIST. Our results also suggested a possible role for circ-BRIP1, circ-EPHB4, and their host genes in the progression of GISTs.
2024-11-01 | GSE188700 | GEO
Project description:Circular RNAs (circRNA) are a novel class of widespread non-coding RNAs (ncRNAs) that regulate gene expression in mammals. Recent studies demonstrate that functional peptides can be encoded by short open reading frames (sORFs) in ncRNAs, including circRNAs. In this study, through deep RNA sequencing on human endometrial cancer (EC) samples and their paired adjacent normal tissues, we uncovered that the circRNA hsa-circ-0000437 is significantly reduced in EC compared to matched paracancerous tissue. The hsa-circ-0000437 contains a sORF encoding a functional peptide termed as CORO1C-47aa. Overexpression of CORO1C-47aa is capable of inhibiting angiogenesis at the initiation stage by suppressing endothelial cell proliferation, migration, and differentiation through competing with TACC3 to bind to ARNT and suppress VEGF. The anti-tumor effects of CORO1C-47aa on EC progression suggest that CORO1C-47aa has a potential value in anti-carcinoma therapies and deserves further investigation.
2022-02-17 | PXD026046 | Pride
Project description:Among the diseases caused by Toll-like receptor 4 (TLR4) abnormal activation by bacterial endotoxin, sepsis is the most dangerous one. The reprogramming of macrophages plays a crucial role in orchestrating the pathogenesis of sepsis. However, the precise mechanism underlying TLR4 activation in macrophages remained incompletely understood. Our studies revealed that upon lipopolysaccharide (LPS) stimulation, CREB-binding protein (CBP) was recruited to the TLR4 signalosome complex and resulted in pronounced acetylation in the TIR domains of TLR4, Myeloid differentiation factor 88 (MyD88) and MyD88 adapter-like (MAL), which significantly enhanced the activation of the NF-κB signaling pathway and polarization of M1 macrophages. In sepsis patients, significantly elevated TLR4-TIR acetylation was detected in CD16+ monocytes combined with elevated expression of M1 macrophage markers and production of pro-inflammatory cytokines. In contrast, histone deacetylase 1 (HDAC1) served as a key deacetylase in the deacetylation of the TIR domain complex. The inhibition of HDAC1 accelerated sepsis-associated syndromes, while the inhibition of CBP alleviated this process. Overall, our findings highlighted the crucial role of TIR domain complex acetylation in the regulation of inflammatory immune response and suggested that the reversible acetylation of the complex emerged as a promising therapeutic target for M1 macrophages during the progression of sepsis.
2024-08-01 | PXD052433 | Pride
Project description:Transcriptome analysis of submandibular glands in female MyD88+/+ and MyD88−/− NOD mice. Sjögren's syndrome (SS) is an autoimmune disease characterized by dysfunction of salivary glands (SGs) and lacrimal glands, which is caused by chronic inflammation associated with autoantibody and autoreactive lymphocyte infiltration. The pathogenic mechanism of SS has not been fully elucidated. Infiltrated lymphocytes form regularized structures similar to lymphoid follicles of secondary lymphoid organs, such as T/B cell compartments, high endothelial venules (HEVs), lymphatic vessels, and germinal centers, therefore being believed as an ectopic lymphoid tissue called tertiary lymphoid organs (TLO). We previously found that deletion of the Toll-like receptor/IL-1 receptor (TLR/IL-1R) adaptor molecule gene Myd88 in SS model mice NOD reduced the frequency of lymphocyte infiltration and HEV formation in SGs. In this study, we analyzed the effect of MyD88 deficiency on lymphoid follicle formation in SGs of NOD mice. Microarray analysis showed decreased expression of genes related to TLO, such as Cxcl13 and Cxcr5, in Myd88-deficient SGs. These results indicate that deficiency of TLR/IL-1R signaling decrease gene expression ot chemokines in SGs, suggesting MyD88-dependent signaling is directly involved in formation of lymphoid follicles in SS.
2021-09-01 | GSE157669 | GEO
Project description:The expression profiles of circRNAs in Jurkats cells, co-cultured with and without ionomycin, were analyzed by next-generation sequencing and validated using real-time polymerase chain reaction. The identified Ca2+ influx-regulated circRNAs were further examined in T cells from 42 patients with SLE and 23 healthy controls. The biological function of specific circRNAs was investigated using transfection and RNA pull-down assay. After validation, we confirmed that the expression levels of circ-ERCC4, circ-NFATC2, circ-MYH10, circ-CAMTA1, circ-ASH1L, circ-SOCS7, and circ-ASAP1 were consistently increased in Jurkat cells following Ca2+ influx. The expression levels of circ-CAMTA1, circ-ASH1L, and circ-ASAP1 were significantly lower in T cells from patients with SLE, with even lower levels observed in those with higher disease activity. Interferon (IFN)-α was found to suppress the expression of circ-CAMTA1. Circ-CAMTA1 bound to pyruvate carboxylase and inhibited its biologic activity. Overexpression of circ-CAMTA1, but not its linear form, significantly decreased extracellular glucose levels. Furthermore, increased expression of circ-CAMTA1, but not its linear form, enhanced IL-2 secretion and the protein expression of NFAT1.
2024-11-06 | GSE278650 | GEO
Project description:Recent research has underscored the significance of circular RNA (circRNA) in various cancers, including neuroblastoma (NB). Specifically, circ-SHPRH, a distinct circRNA, has emerged as an inhibitor of tumor growth through its ability to sequester miRNAs or produce the SHPRH-146aa protein. To explore circ-SHPRH's involvement in NB and its potential application in gene therapy, this study examined its expression in 94 NB tissues and cell lines (SK-N-BE(2), SH-SY5Y, CHLA-255) using real-time PCR and fluorescence in situ hybridization (FISH). Functional assays encompassing both overexpression and knockdown experiments in NB cell lines, as well as in vivo investigations, were conducted. RNA-seq analysis revealed a correlation between circ-SHPRH and the P21 (CDKN1A) pathway, a pivotal cell cycle regulator. Validation through PCR and other techniques confirmed that circ-SHPRH upregulated P21 expression. Furthermore, the regulatory role of circ-SHPRH in the P21-CDK pathway was corroborated through SHPRH-146aa expression. Notably, adenovirus-mediated overexpression of circ-SHPRH effectively curbed NB tumor growth in NSG mice, while combining circ-SHPRH with everolimus exhibited potential for NB treatment. This study elucidates the remarkable significance of circ-SHPRH in NB and its prospective utility in gene therapy, thereby paving the way for innovative therapeutic approaches.
2024-07-19 | GSE244294 | GEO