TfR1 binding with H-ferritin nanocarrier achieves prognostic diagnosis and enhances the therapeutic efficacy in clinical gastric cancer
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ABSTRACT:
PROVIDER: PRJNA600833 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR10875546_1.fastq.gz | Fastqsanger.gz | |||
| SRR10875546_2.fastq.gz | Fastqsanger.gz | |||
| SRR10875547_1.fastq.gz | Fastqsanger.gz | |||
| SRR10875547_2.fastq.gz | Fastqsanger.gz |
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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: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 of TfR1 was assessed in 178 GC tissues by using a magneto-HFn nanoparticle-based immunohistochemistry method. The therapeutic effects of doxorubicin-loaded HFn nanocarriers (HFn-Dox) were 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 features, which enhanced tumor formation and 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 with IFN-γ. Western blot results demonstrated that TfR1-knockout GC cells upregulated Akt and STAT3 signaling. Moreover, in TfR1-positive GC-PDX models, the 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 possessed tumor-aggressive features; (ii) TfR1-positive cells can be killed by HFn drug nanocarrier. Given the heterogeneity of GC, HFn drug nanocarrier combined with other therapies toward TfR1-negative cells (such as small molecules or immunotherapy) will be a new option for GC treatment.
| S-EPMC7002446 | biostudies-literature
Project description:Transferrin receptor 1 (TfR1), a widely expressed type II transmembrane glycoprotein located on the plasma membrane, is well known for its established role in cellular iron uptake. Nevertheless, emerging evidence implies that TfR1 exhibits previously unrecognized noncanonical functions. Herein, we demonstrated the nuclear translocation of TfR1 and revealed the interaction between TfR1 and p53 within the nucleus. Through comprehensive analyses at the proteomic, genomic, and transcriptomic levels, we demonstrated that this interaction significantly influences the transcriptional activity of p53 on its downstream target genes, which are highly enriched in DNA damage repair functions. Specifically, our investigation revealed the indispensable role of nuclear TfR1 in the regulation of the nucleotide excision repair (NER) pathway, exemplified by the transcriptional regulation of XPC. Notably, both in vitro and in vivo results revealed a positive regulatory role of TfR1 in the NER pathway. Subsequent phenomic analysis of clinical colorectal tumor samples confirmed a positive correlation between nuclear TfR1 levels and tumor malignancy, aggressive features, and metastasis. Collectively, our findings highlight the non-classical function of TfR1, emphasizing its importance in the regulation of gene expression, as well as tumor progression.
2025-07-08 | PXD063330 | Pride
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: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:The retention of galactose-deficient IgA1 (Gd-IgA1) in the glomerular mesangium is a hallmark of IgA nephropathy (IgAN). The immune complex formed by Gd-IgA1 binds to transferrin receptor 1 (TfR1) and deposits on mesangial cell, inducing cell proliferation, inflammatory response, matrix secretion, etc., causes organic damage and dysfunction of the kidney. Even though, the mechanism of how Gd-IgA1 recognize and bind to TfR1 is unclear. In this experiment, we ami to determine the specific interaction region responsible for Gd-IgA1 and TfR1. We prepared a complex of Gd-IgA1 and TfR1 by incubating the two proteins under acidic conditions and stabilizing it using the chemical cross-linking agent glutaraldehyde. And then, the gel bands corresponding to the Gd-IgA1-TfR1 complex was exexcised from the SDS-PAGE gel and analyzed by high-resolution mass spectrometry. This analysis identified fragments containing the hinge peptide sequence, with the R276 residue interacting with the E350 and D356 residues in the apical domain of TfR1. Our results reveal that the hinge peptide of Gd-IgA1 interacts specifically with the apical domain of TfR1.
2025-07-14 | PXD063709 | Pride
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: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