Mechanism of sensitivity and resistance to treatment with an TfR1 antibody fusion protein in B-cell malignancies
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE14754 | GEO | 2010/02/09
SECONDARY ACCESSION(S): PRJNA112247
REPOSITORIES: GEO
Similar Datasets
Project description:The transferrin receptor 1 (TfR1), encoded by TFRC gene, is the gatekeeper of cellular iron uptake for cells. A variety of molecular mechanisms are at work to tightly regulate TfR1 expression, and abnormal TfR1 expression was associated with diseases. In the current study, to figure out the regulation pattern of TfR1, we cloned and overexpressed human TFRC gene in HeLa cells. RNA-sequencing (RNA-seq) was used to analyze the global transcript level on overexpression-treated (OE) and normal control (NC) cell samples. 1669 differentially expressed genes (DEGs) were identified between OE and NC, and Gene ontology (GO) analysis for DEGs were carried out. It was found that lots of DEGs were associated with ion transmembrane transport and immunity. Moreover, the network was constructed on basis of DEGs regulating ion transport and immunity, the results revealed that TFRC was the node gene of the network, further suggesting that precisely controlled TfR1 expression might be not only essential for iron homeostasis, but also globally important for cell physiology, including ion transport and immunity.
2021-08-27 | GSE130048 | GEO
Project description:H-ferritin (HFn) nanocarrier is emerging as a promising theranostic platform for tumor diagnosis and therapy, which can specifically target tumor cells via binding transferrin receptor 1 (TfR1). This led us to investigate the therapeutic function of TfR1 in GC. The clinical significance ofTfR1 was assessed in 178 GC tissues using a magneto-HFn nanoparticle-based immunohistochemistry method. Therapeutic effects of doxorubicin-loaded HFn nanocarriers evaluated on TfR1 positive GC patient-derived xenograft (GC-PDX) models. The biological function of TfR1 was investigated through in vitro and in vivo assays. TfR1 was upregulated (73.03%) in GC tissues and reversely correlated with patient outcome. TfR1 negative sorted cells exhibited tumor-initiating feature, which enhanced tumor formation in vitro and in vivo, migration/invasion, whereas TfR1 positive sorted cells showed significant proliferation ability. Knockout of TfR1 in GC cells also enhanced cell invasion. TfR1 deficient cells displayed immune escape by upregulating PD-L1, CXCL9 and CXCL10, when disposed by IFN-γ. Western blot results demonstrated that knockout of TfR1 in GC cells upregulated Akt and STAT3 signaling. Moreover, in TfR1 positive GC-PDX models, HFn-Dox group significantly inhibited tumor growth and increased mouse survival compared with that of free-Dox group. TfR1 could be a potential prognostic and therapeutic biomarker for GC: (i) TfR1 reversely correlated with patient outcome and its negative cells possess tumor aggressive features; (ii) TfR1 positive cells can be killed by H-ferritin nanocarrier. Given the heterogeneity of GC, HFn nanocarrier combined with other therapies towards TfR1 negative cells (such as: small molecule or immunotherapy etc.) will be new options for GC treatment.
2023-01-01 | GSE143497 | GEO
Project description:Tfr1 is important for iron uptake in red blood cells. We deleted Tfr1 in skeletal muscle to determine the role of Tfr1 in iron uptake in skeletal muscle. We used microarrays to identify global gene changes associated with deletion of Tfr1 in skeletal muscle
2015-05-08 | GSE68675 | GEO
Project description:We deleted Tfr1 in the heart to determine the role of Tfr1 in iron uptake in normal cardiac funciton We used microarrays to identify global gene changes associated with deletion of Tfr1 in skeletal muscle
2015-05-12 | GSE68745 | GEO
Project description:We deleted Tfr1 in the heart to determine the role of Tfr1 in iron uptake in normal cardiac funciton We used microarrays to identify global gene changes associated with deletion of Tfr1 in skeletal muscle We isolated RNA from WT and Tfr1 KO hearts at both postnatal day 5 and postnatal day 10.RNA was labaled and hibridized to Affymetrics microarrays.
2015-05-12 | E-GEOD-68745 | biostudies-arrayexpress
Project description:Tfr1 is important for iron uptake in red blood cells. We deleted Tfr1 in skeletal muscle to determine the role of Tfr1 in iron uptake in skeletal muscle. We used microarrays to identify global gene changes associated with deletion of Tfr1 in skeletal muscle We used skeletal muscle and liver from wild type and Tfr1 skeletal muscle KO mice at postnatal day 5 and postnatal day 9. mRNA was extracted from the tissues, labaled and hibridized to Affymetrics microarrays.
2015-05-08 | E-GEOD-68675 | biostudies-arrayexpress
Project description:Iron is essential for all cells but is toxic in excess, so iron absorption and distribution are tightly regulated. Serum iron is bound to transferrin and primarily enters erythroid cells via receptor-mediated endocytosis of the transferrin receptor (Tfr1). Tfr1 is essential for developing erythrocytes and reduced Tfr1 expression is associated with anemia. The transcription factors STAT5A/B are activated by many cytokines, including erythropoietin. Stat5a/b-/- mice are severely anemic and die perinatally, but no link has been made to iron homeostasis. To study the function of STAT5A/B in vivo, we deleted the floxed Stat5a/b locus in hematopoietic cells with a Tie2-Cre transgene. These mice exhibited microcytic, hypochromic anemia, as did lethally irradiated mice transplanted with Stat5a/b-/- fetal liver cells. Flow cytometry and RNA analyses of erythroid cells from mutant mice revealed a 50% reduction in Tfr1 mRNA and protein. We detected STAT5A/B binding sites in the first intron of the Tfr1 gene and found that expression of constitutively active STAT5A in an erythroid cell line increased Tfr1 levels. Chromatin immunoprecipitation experiments confirmed the binding of STAT5A/B to these sites. We conclude that STAT5A/B is an important regulator of erythroid progenitor iron uptake via its control of Tfr1 transcription. Keywords: genetic modification
2008-06-13 | GSE11777 | GEO
Project description:In the current study, to figure out the regulation pattern of TfR1, we knocked down TFRC expression level by shRNA in HeLa cells. RNA-sequencing (RNA-seq) was used to analyze the global transcript level and alternative splicing (AS) on knockdown-treated (KD) and normal control (NC) cell samples. 629 differentially expressed genes (DEGs) were identified between OE and NC, and Gene ontology (GO) and KEGG analysis for DEGs were carried out. It was found that multiple DEGs were involved in O-glycan processing, protein modification, response to hypoxia and ATP catabolic process, indicating the down-regulated expression of TfR1 extensively disturbed cell physiology.
2022-05-08 | GSE131598 | GEO
Project description:Iron is essential for all cells but is toxic in excess, so iron absorption and distribution are tightly regulated. Serum iron is bound to transferrin and primarily enters erythroid cells via receptor-mediated endocytosis of the transferrin receptor (Tfr1). Tfr1 is essential for developing erythrocytes and reduced Tfr1 expression is associated with anemia. The transcription factors STAT5A/B are activated by many cytokines, including erythropoietin. Stat5a/b-/- mice are severely anemic and die perinatally, but no link has been made to iron homeostasis. To study the function of STAT5A/B in vivo, we deleted the floxed Stat5a/b locus in hematopoietic cells with a Tie2-Cre transgene. These mice exhibited microcytic, hypochromic anemia, as did lethally irradiated mice transplanted with Stat5a/b-/- fetal liver cells. Flow cytometry and RNA analyses of erythroid cells from mutant mice revealed a 50% reduction in Tfr1 mRNA and protein. We detected STAT5A/B binding sites in the first intron of the Tfr1 gene and found that expression of constitutively active STAT5A in an erythroid cell line increased Tfr1 levels. Chromatin immunoprecipitation experiments confirmed the binding of STAT5A/B to these sites. We conclude that STAT5A/B is an important regulator of erythroid progenitor iron uptake via its control of Tfr1 transcription. Experiment Overall Design: Isolated Ter119-positive fetal liver cells from three to five E14.5 embryos of the same genotype were combined, and total RNA was extracted using TRIzol reagent (Life Technologies) with two additional ethanol precipitations. RNA quality was verified using an Agilent Bioanalyzer (Agilent Technologies). Microarray analyses were performed using Affymetrix Mouse Genome 430 2.0 array GeneChips (Affymetrix). Up- and down-regulated genes were selected based on P values of <0.05 and fold changes of >1.5 or -1.5 as assessed by ANOVA using Partek Pro software (Partek). To determine specific pathways, gene pathway analysis was obtained using the statistically significant gene list (P<0.05) represented on the chip.
2008-10-21 | E-GEOD-11777 | biostudies-arrayexpress
Project description:The role of Tfr1 in non-erythroid tissues remains elusive due to the embryonic lethality of the Tfr1 global knockout mouse model. To bypass this problem, we generated a mouse model in which Tfr1 was conditionally deleted in intestinal epithelial cells (IECs). These mice developed severe IEC disruption, characterized by blunted villi, edema, loss of proliferative intervillus IECs, accumulation of lipids, and early neonatal lethality. Strikingly, a wide range of genes associated with epithelial-to-mesenchymal transition were highly upregulated in IEC lacking Tfr1. Additionally, candidate vesicular transport and sorting genes implicated in lipid absorption and trafficking were downregulated. Surprisingly, the presence of a mutant allele of Tfr1, which is unable to bind to iron-loaded transferrin, was capable of rescuing the lethality, intestinal epithelial homeostasis, and proliferation in a majority of the Tfr1 conditional knockout mice.
2015-05-19 | GSE68984 | GEO