LncRNA-NFYB axis drives immune suppression to promote HCC progression by a positive feedback
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE154509 | GEO | 2026/07/01
REPOSITORIES: GEO
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Project description:Palmitic acid (PA) absorption from the intestine is increased in metabolic dysfunction-associated steatohepatitis (MASH). It induces endoplasmic reticulum (ER) stress and interleukin-1 beta (IL-1β) production in hepatic stellate cells (HSCs). Protein kinase R-like endoplasmic reticulum kinase (PERK) is an ER stress sensor protein involved in HSC activation and liver fibrosis. However, its role in HSCs during hepatocellular carcinoma (HCC) progression remains unclear. This study clarified the process of IL-1β production via PERK in HSCs and explored the mechanism underlying MASH-related HCC progression. HSCs were treated with PA or transfected with PERK small-interfering RNA (siRNA) or PERK plasmid. Proliferation, scratch, and Transwell assays were performed on HCC cells cultured in the conditioned medium (CM) from HSCs. PA treatment increased PERK and IL-1β expressions in HSCs. PERK knockdown decreased IL-1β expression, while its overexpression increased it in HSCs. The CM from PA-treated HSCs showed elevated IL-1β levels and enhanced HCC cells’ proliferation, migration, and invasion; however, these effects were suppressed by PERK knockdown in HSCs. RNA-sequencing analysis revealed that p38δ mitogen-activated protein kinase (MAPK) is the intermediate molecule between PERK and IL-1β in HSCs. In the tumor microenvironment of MASH-related HCC, PERK in HSCs promotes HCC progression via the p38δ MAPK/IL-1β axis.
2025-06-07 | GSE292002 | GEO
Project description:Chronic inflammation is known to associate with prostate cancer development, but how epithelium-associated cancer initiating events cross-talk to inflammatory cells during prostate cancer initiation and progression is largely unknown. Using the Pten null murine prostate cancer model, we show an expansion of Gr-1+CD11b+ myeloid-derived suppressor cells (MDSCs) occurring intra-prostatically immediately following epithelium-specific Pten deletion without expansion in hematopoietic tissues. This MDSC expansion is accompanied by sustained immune suppression. Prostatic Gr-1+CD11b+ cells, but not those isolated from the spleen of the same tumor bearing mice, suppress T cell proliferation and express high levels of Arginase 1 and iNOS. Mechanistically, loss of PTEN in the epithelium leads to a significant upregulation of genes within the inflammatory response and cytokine-cytokine receptor interaction pathways, including Csf-1 and IL-1β, two genes known to induce MDSC expansion and immunosuppressive activities. Treating Pten null mice with the selective CSF-1 receptor inhibitor GW2580 decreases MDSC infiltration and relieves the associated immunosuppressive phenotype. Our study indicates that epithelium-associated tumor initiating events trigger the secretion of inflammatory cytokines and promote localized MDSC expansion and immune suppression, thereby promoting tumor progression Custom Agilent 4x44K whole mouse genome expression oligonucleotide microarrays were used to measure transcript levels in murine Pten null prostate cancer cell lines. Benign mouse prostate epithelia as wild type control against cell lines. Each cohort had three biological replicates.
2014-04-03 | E-GEOD-56468 | biostudies-arrayexpress
Project description:Chronic inflammation is known to associate with prostate cancer development, but how epithelium-associated cancer initiating events cross-talk to inflammatory cells during prostate cancer initiation and progression is largely unknown. Using the Pten null murine prostate cancer model, we show an expansion of Gr-1+CD11b+ myeloid-derived suppressor cells (MDSCs) occurring intra-prostatically immediately following epithelium-specific Pten deletion without expansion in hematopoietic tissues. This MDSC expansion is accompanied by sustained immune suppression. Prostatic Gr-1+CD11b+ cells, but not those isolated from the spleen of the same tumor bearing mice, suppress T cell proliferation and express high levels of Arginase 1 and iNOS. Mechanistically, loss of PTEN in the epithelium leads to a significant upregulation of genes within the inflammatory response and cytokine-cytokine receptor interaction pathways, including Csf-1 and IL-1β, two genes known to induce MDSC expansion and immunosuppressive activities. Treating Pten null mice with the selective CSF-1 receptor inhibitor GW2580 decreases MDSC infiltration and relieves the associated immunosuppressive phenotype. Our study indicates that epithelium-associated tumor initiating events trigger the secretion of inflammatory cytokines and promote localized MDSC expansion and immune suppression, thereby promoting tumor progression. Laser-capture microdissection was used to extract epithelial cells from murine benign and Pten null prostate tumors. Their transcript levels were measured by the custom Agilent 4x44K whole mouse genome expression oligonucleotide microarrays. Each cohort had three biological replicates.
2014-04-03 | E-GEOD-56469 | biostudies-arrayexpress
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2023-05-03 | GSE189941 | GEO
Project description:Fibroblasts display significant heterogeneity and exhibit distinct gene expression profiles under different cytokine stimulations. We utilized RNA-seq to analyze the expression profile differences between control and IL-1β stimulated fibroblasts（ n=3）. Our analysis revealed 1756 differentially expressed genes between WT and Smyd1-KO hearts [adjusted P-value <0.05, |log2(fold change)| > 0.5]. Among these, 755 genes were upregulated, and 843 genes were downregulated in IL-1β stimulated human dermal fibroblasts. Notably, IL-1β stimulation can induce fibroblast differentiation into pro-inflammatory fibroblasts, characterized by the expression of neutrophil-related chemokines (CXCL1, CXCL2, CXCL3), ferroptosis-related genes (PTGS2, TNFAIP6), and pro-inflammatory cytokines (IL6). Our findings lay the groundwork for understanding the IL-1β-induced fibroblast expression of specific gene profiles.
2025-07-07 | GSE265838 | GEO
Project description:Purpose: Fibroblast-like synoviocytes (FLSs) play a crucial role in maintaining joint homeostasis by secreting matrix components and lubricin [1, 2]. However, under inflammatory conditions, FLSs contribute to tissue damage, leading to osteoarthritis (OA) [3]. The specific genes and pathways driving this inflammatory response in FLSs remain poorly understood. This study aims to elucidate the transcriptome-wide responses of FLSs to IL-1β, a master proinflammatory cytokine, and to investigate the modulatory effects of TGF-β1 on the expression of chemokine transcripts in a model of inflammatory arthritis. Methods: Normal FLSs were isolated from synovial explants obtained from patients undergoing anterior cruciate ligament reconstruction surgery. The isolated cells were expended and exposed to IL-1β (10 ng/mL) for 24 hours to simulate inflammatory arthritis. Changes in gene expression were assessed by RNA-seq and validated through Fluidigm multiplex real-time PCR [4]. In a separate experiment, FLSs were pre-treated with IL-1β as above and subsequently exposed to TGF-β1 (10 ng/mL) for an additional 48 hours to evaluate its potential modulatory effects on the expression of chemokines as determined by Fluidigm multiplex real-time PCR. Results: IL-1β-treated FLSs showed a significant upregulation of numerous chemokines, including CCL20, CCL5, CXCL8, CXCL6, CXCL4, CXCL1, CXCL3, and CXCL2. Additionally, transcripts associated with inflammatory arthritis, such as CSF2, CSF3, MMP12, IL1B, and LIPM, were elevated (Table 1). Expression of KRT14, KRT19, KRT18, and several other anabolic and matrix genes was significantly reduced with IL-1β-treatment (Table 1). The genes highly expressed in IL-1β-treated cells were enriched for NFkB signaling, cytokine and chemokine signaling, TNF signaling, and necroptosis, whereas genes lowly expressed were enriched for the immune system. TGF-β1 treatment exhibited strong anti-inflammatory effects, modulating the expression of numerous chemokines and inflammatory mediators, thereby counteracting the IL-1β-induced inflammatory response in FLSs (Fig. 1). Moreover, the expression of the chemokine transcription factor C/EBPβ was also high (about twofold) in IL-1β-treated cells, which was reduced by half after TGF-β1 treatment, suggesting that TGF-β1 exerts its anti-chemokine effects through transcriptional repression of C/EBPβ in FLSs. Conclusions: This is the first study to examine the effects of IL-1β treatment in FLS derived from patients with ACL tears. Our data show that IL-1β significantly influences the expression of CC and CXC chemokine transcripts in FLSs, mirroring findings in chondrocytes, where human adult chondrocytes exhibit increased expression of CC and CXC chemokines [5]. Our finding that TGF-β1 effectively mitigates the inflammatory responses induced by IL-1β, potentially through suppression of transcription factor C/EBPβ, is novel. It highlights the potential of TGF-β1 as a therapeutic target for OA-related inflammatory conditions. These findings warrant further mechanistic studies to understand the inflammatory dynamics of FLSs in inflammatory arthritis.
2026-03-15 | GSE293257 | GEO
Project description:Background: The cancer-related mortality of primary liver cancer ranks third globally, and hepatocellular carcinoma (HCC) is predominant, posing a serious threat to patients' health. Understanding HCC's pathogenesis and target molecules is crucial for early diagnosis and prognosis. Extracellular vesicles (EVs) and their carried miRNAs impact tumor progression. This study aims to investigate miR-183-5p in HCC cell-derived EVs on angiogenesis, progression, and metastasis, and provide diagnostic and therapeutic evidence. Methods: q-PCR was used to evaluate the expression of miR-183-5p in HCC tissue and plasma EV samples. Contrast-enhanced ultrasound and The Cancer Genome Atlas evaluated its correlation with angiogenesis and prognosis. In vitro, cell counting kit-8 (CCK-8), colony formation, transwell, tube formation, and permeability assays examined the effect of HCC cell-derived EVs on human umbilical vein endothelial cells (HUVECs). Subcutaneous tumor and lung metastasis models in nude mice verified it in vivo effects. RNA sequencing and databases predicted downstream genes and pathways, and dual luciferase and western blotting assays verified binding and activation. Conditioned medium from treated HUVECs was used on HCC cells, and chemokine levels measured. The CCL20/CCR6 axis effect was studied in vitro and in vivo by knocking down CCR6. Results: This study revealed the abnormal upregulation of miR-183-5p in both tissues and plasma EVs from patients with HCC, and its association with unfavorable prognosis. In vivo experiments, the promoting effects of miR-183-5p in HCC cell-derived EVs on the progression, metastasis and angiogenesis were verified by employing subcutaneous tumor formation models and lung metastasis models in nude mice. We demonstrated that miR-183-5p in HCC cell-derived EVs induced HUVECs proliferation, migration, angiogenesis and permeability by downregulating SIK1 expression and activating the PI3K/AKT signaling pathway in vitro. Moreover, stimulated HUVECs could secrete the chemokine CCL20 and induce HCC progression and metastasis through the CCL20/CCR6 signal pathway in vitro and in vivo. Conclusion: The findings indicated that miR-183-5p delivered by EVs from HCC cells is crucial in mediating the communication between HUVECs and HCC cells by modulating the SIK1/PI3K/AKT and CCL20/CCR6 signaling pathways, and EVs-miR-183-5p might be a potential therapeutic target for HCC patients.
2025-03-25 | GSE289187 | GEO
Project description:Atopic dermatitis (AD) is a debilitating inflammatory skin disorder. Biologics targeting the IL-4/IL-13 axis are effective in AD, but there is still a large proportion of patients that do not respond to IL-4R blockade. Further exploration of potentially pathogenic T cell-derived cytokines in AD may lead to new effective treatments. This study aimed to investigate the downstream effects of IL-26 on skin in the context of type 2 skin inflammation. We found that IL-26 alone exhibited limited inflammatory activity in skin. However, in presence of IL-1β, IL-26 potentiated the secretion of TSLP, CXCL1 and CCL20 from human epidermis through JAK/STAT signaling. Moreover, in an in vivo AD-like skin inflammation model, IL-26 exacerbated skin pathology and locally increased type 2 cytokines, most notably of Il13 in skin T helper cells. Neutralization of IL-1β abrogated IL-26-mediated effects, indicating that the presence of IL-1β is required for full IL-26 downstream action in vivo. These findings suggest that the presence of IL-1β enables IL-26 to be a key amplifier of inflammation in the skin. As such, IL-26 may contribute to the development and pathogenesis of inflammatory skin disorders such as AD.
2024-01-10 | GSE228860 | GEO
Project description:Chronic inflammation is known to associate with prostate cancer development, but how epithelium-associated cancer initiating events cross-talk to inflammatory cells during prostate cancer initiation and progression is largely unknown. Using the Pten null murine prostate cancer model, we show an expansion of Gr-1+CD11b+ myeloid-derived suppressor cells (MDSCs) occurring intra-prostatically immediately following epithelium-specific Pten deletion without expansion in hematopoietic tissues. This MDSC expansion is accompanied by sustained immune suppression. Prostatic Gr-1+CD11b+ cells, but not those isolated from the spleen of the same tumor bearing mice, suppress T cell proliferation and express high levels of Arginase 1 and iNOS. Mechanistically, loss of PTEN in the epithelium leads to a significant upregulation of genes within the inflammatory response and cytokine-cytokine receptor interaction pathways, including Csf-1 and IL-1β, two genes known to induce MDSC expansion and immunosuppressive activities. Treating Pten null mice with the selective CSF-1 receptor inhibitor GW2580 decreases MDSC infiltration and relieves the associated immunosuppressive phenotype. Our study indicates that epithelium-associated tumor initiating events trigger the secretion of inflammatory cytokines and promote localized MDSC expansion and immune suppression, thereby promoting tumor progression.
2014-04-03 | GSE56469 | GEO
Project description:Chronic inflammation is known to associate with prostate cancer development, but how epithelium-associated cancer initiating events cross-talk to inflammatory cells during prostate cancer initiation and progression is largely unknown. Using the Pten null murine prostate cancer model, we show an expansion of Gr-1+CD11b+ myeloid-derived suppressor cells (MDSCs) occurring intra-prostatically immediately following epithelium-specific Pten deletion without expansion in hematopoietic tissues. This MDSC expansion is accompanied by sustained immune suppression. Prostatic Gr-1+CD11b+ cells, but not those isolated from the spleen of the same tumor bearing mice, suppress T cell proliferation and express high levels of Arginase 1 and iNOS. Mechanistically, loss of PTEN in the epithelium leads to a significant upregulation of genes within the inflammatory response and cytokine-cytokine receptor interaction pathways, including Csf-1 and IL-1β, two genes known to induce MDSC expansion and immunosuppressive activities. Treating Pten null mice with the selective CSF-1 receptor inhibitor GW2580 decreases MDSC infiltration and relieves the associated immunosuppressive phenotype. Our study indicates that epithelium-associated tumor initiating events trigger the secretion of inflammatory cytokines and promote localized MDSC expansion and immune suppression, thereby promoting tumor progression
2014-04-03 | GSE56468 | GEO