Bulk RNA-seq of colonic epithelial stem cell-derived organoids from healthy epithelial HO-1 knockout and control mice exposed to hemin vs vehicle
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE312912 | GEO | 2025/12/12
REPOSITORIES: GEO
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Project description:Heme, an iron-containing prosthetic group found in many proteins, carries out diverse biological functions such as electron transfer, oxygen storage and enzymatic reactions. Hemin, the oxidised form of heme, is used to treat porphyria and also to activate heme-oxygenase (HO) which catalyses the rate-limiting step in heme degradation. Our group has previously demonstrated that hemin displays antitumor activity in breast cancer (BC). The aim of this work has been to study the effect of hemin on protein expression modifications in a BC cell line to gain insight into the molecular mechanisms of hemin antitumor activity. For this purpose, we carried out proteome analysis by Mass Spectrometry (MS) which showed that 1309 proteins were significantly increased in hemin-treated cells, including HO-1 and the proteases that regulate HO-1 function, and 921 proteins were significantly decreased. Furthermore, the MS-data analysis showed that hemin regulates the expression of heme- and iron- related proteins, adhesion and cytoskeletal proteins, cancer signal transduction proteins and enzymes involved in lipid metabolism. By biochemical and cellular studies, we further corroborated the most relevant in-silico results. Altogether, these results show the multiple physiological effects that hemin treatment displays in BC and demonstrate its potential as anticancer agent.
2023-07-20 | PXD036701 | Pride
Project description:Bulk RNA-seq of colonic epithelial stem cell-derived organoids from healthy epithelial HO-1 knockout and control mice exposed to hemin vs vehicle
| PRJNA1377590 | ENA
Project description:Regulatory heme is known to control cellular behavior by regulating the activities of hemoproteins. We hypothesized that increased levels of regulatory heme may drive T cell exhaustion. To test this, we first confirmed that treatment with hemin, a heme analog, effectively increased intracellular regulatory heme levels in T cells. To evaluate the transcriptional changes in CD8+ T cells treated with hemin, we conducted RNA sequencing on CD8+ T cells with and without exogenous hemin treatment. The RNA-seq data revealed that hemin treatment strongly modulated gene expression patterns associated with terminally exhausted T cells. Pathway enrichment analysis further revealed that hemin suppressed pathways involved in proliferation and cytokine production while altering metabolic processes, such as cholesterol efflux and fatty acid biosynthesis, which are known to regulate T cell function. These results suggest that increased levels of regulatory heme drive T cell exhaustion differentiation.
2026-01-25 | GSE312103 | GEO
Project description:Many phytopathogens such as Ustilago maydis rely on their hosts for nutrients during disease. In this study, we tried to identify key genes involved in heme uptake and gain a deeper understanding of the transcriptional response to hemin treatment. We observed upregulations in ergosterol biosynthesis pathway as well as identified an Abc1 protein with pleitropic contributions to cell surface functions.
2024-11-06 | GSE265973 | GEO
Project description:Metabolic adaptation refers to the regulation of cellular metabolism to prevent tissue dysfunction in response to different forms of stress. Heme, an iron-containing porphyrin, is indispensable for oxygen transport and for the activity of hemoproteins such as catalases. Cytotoxic “labile” heme is readily degraded by two distinct heme oxygenases (HO). The conditional deletion of Hmox-1, the gene encoding the inducible heme-degrading enzyme heme oxygenase (HO)-1, impairs metabolic adaptation to malaria and to polymicrobial infection. Embryonic deficiency in HO-1 is partially lethal in mice and surviving animals show progressive chronic inflammatory disease making them an unsuitable model to study metabolic adaptation. Here we found that mice with an inducible deletion of Hmox1 (Hmox1R26Δ/Δ) but not control mice rapidly succumbed to sterile hemolytic stress. Mortality was associated with heme-driven kidney failure, hypoglycemia, and disruption of adaptive thermoregulation. RNA sequencing and targeted metabolomics combined with data-driven in silico metabolic modeling revealed that failed renal metabolic adaptation is driven by altered oxidative phosphorylation and impaired pentose phosphate pathway. Heme-induced kidney failure and mortality in Hmox1R26Δ/Δ mice was not prevented with impairment of the inflammatory response, nor with antioxidants. Our results emphasize the critical importance of Hmox1 expression in hemolytic stress leading to acute kidney injury and death.
2025-12-02 | GSE246570 | GEO
Project description:The heme catabolism pathway is often elevated in aggressive cancers; however, the impact of this pathway and some of its byproducts on the tumor microenvironment remain largely unknown. In human breast cancers, tumor expression of the heme catabolizing enzyme heme oxygenase-1 (HO-1/HMOX1) is positively associated with macrophage abundance. In mouse mammary tumors, knockdown of Hmox1 significantly decreased tumor growth and lung metastasis. Analysis of mammary tumor interstitial fluid compared to matching plasma revealed that the heme metabolite bilirubin was elevated intratumorally, which could be partially reversed via Hmox1 knockdown. Further investigation revealed that bilirubin nearly ablates macrophage engulfment of dead tumor cells and significantly increases macrophage T cell suppression. Mammary tumors harboring Hmox1 knockdown had a significant decrease in tumor growth rate and number of pro-metastatic CD206+ macrophages upon treatment with αPD-1. Depletion of intratumoral bilirubin levels impacts pro-tumor macrophage populations, particularly in combination with immunotherapy, demonstrating that heme catabolism and bilirubin act as immunomodulators in cancer.
2026-04-24 | MTBLS14278 | MetaboLights
Project description:The aim was to determine the effect of heme oxygenase-1 (HO-1) overexpression on microRNA transcriptome in human non-small cell lung carcinoma cell line (NCI-H292). Since the cells of different HO-1 genotypes were used (cells are after retroviral transduction with empty vector with normal level of HO-1 or retroviral transduction with vector harboring HO-1), it is possible get the comprehensive answer which microRNAs are regulated by HO-1.
2013-04-27 | GSE37779 | GEO
Project description:Kidneys are pivotal organ in iron redistribution and can be severely damaged in the course of hemolysis. In our previous studies, we observed that induction of hyper- tension with angiotensin II (Ang II) combined with simvastatin administration results in a high mortality rate or the appearance of signs of kidney failure in heme oxy- genase-1 knockout (HO-1 KO) mice. Here, we aimed to address the mechanisms underlying this effect, focusing on heme and iron metabolism. We show that HO-1 deficiency leads to iron accumulation in the renal cortex. Higher mortality of Ang II and simvastatin-treated HO-1 KO mice coincides with in- creased iron accumulation and the upregulation of mucin-1 in the proximal convoluted tubules. In vitro studies showed that mucin-1 hampers heme- and iron-related oxidative stress through the sialic acid residues. In parallel, knock-down of HO-1 induces the glutathione pathway in an NRF2-depedent manner, which likely protects against heme-induced toxicity. To sum up, we showed that heme degradation during heme overload is not solely dependent on HO-1 enzymatic activity, but can be modulated by the glutathione pathway. We also identified mucin-1 as a novel redox regulator. The results suggest that hypertensive patients with less active HMOX1 alleles may be at higher risk of kidney injury after statin treatment.
2023-06-19 | PXD042995 | Pride
Project description:DEAD-box helicase 24 (DDX24) is a member of the DEAD-box protein family, which is essential for various aspects of RNA metabolism. DDX24 has been reported to play a role in ribosome biogenesis, transcription, and mRNA stability. Previous studies have implicated the functions of DDX24 in innate immunity, vascular malformation, cell growth, and cancer progression. Here, we describe a novel function of DDX24 in regulating the oxidative stress response and protecting cells from apoptosis. Our research revealed that DDX24 specifically regulates the expression of the heme oxygenase-1 (HO-1) gene, as determined by RNA sequencing analysis. HO-1 is responsible for degrading heme into carbon monoxide (CO), biliverdin, and ferrous ion (Fe2+), thereby exerting anti-apoptotic and anti-oxidative effects. We validated the regulation of HO-1 by DDX24 in both DDX24-depleted and DDX24-overexpressing HEK293 cells. Our findings indicate that DDX24 is involved in the induction of HO-1 expression under oxidative stress conditions. Importantly, DDX24 regulates the transcription of HO-1 instead of its mRNA stability, likely acting at the promoter and enhancer E1 region of the HO-1 gene. Furthermore, DDX24 depletion in HEK293T cells inhibits cell viability. DDX24 exerts both anti-apoptotic and anti-oxidative effects during oxidative stress. These results suggest that DDX24 plays a crucial role in protecting cells from oxidative stress-induced damage by regulating the transcription of HO-1.
2026-01-01 | GSE299414 | GEO
Project description:The aim was to determine the effect of heme oxygenase-1 (HO-1) overexpression on microRNA transcriptome in human non-small cell lung carcinoma cell line (NCI-H292). Since the cells of different HO-1 genotypes were used (cells are after retroviral transduction with empty vector with normal level of HO-1 or retroviral transduction with vector harboring HO-1), it is possible get the comprehensive answer which microRNAs are regulated by HO-1. Confluent NCI-H292 cells that contain EV-ctrl or overexpressing HO-1. Pool of reference cells are cells untreated and treated with 10 ng/ml TNF-M-NM-1 for 6 hours before RNA isolation. The samples are biological triplicates - three independent experiments were performed at different time points for all cell lines. Total number of the presented samples is 6.
2013-04-27 | E-GEOD-37779 | biostudies-arrayexpress