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Nrf2-regulated L-2-hydroxyglutarate sensitizes erythroid cells to ferroptosis in sickle cell disease

ABSTRACT: Nrf2-regulated L-2-hydroxyglutarate sensitizes erythroid cells to ferroptosis in sickle cell disease

PROVIDER: PRJNA779947 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR16929285_1.fastq.gz	Fastqsanger.gz
	SRR16929285_2.fastq.gz	Fastqsanger.gz
	SRR16929286_1.fastq.gz	Fastqsanger.gz
	SRR16929286_2.fastq.gz	Fastqsanger.gz
	SRR16929287_1.fastq.gz	Fastqsanger.gz

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Nrf2-regulated L-2-hydroxyglutarate sensitizes erythroid cells to ferroptosis in sickle cell disease

Project description:SCD had hemolysis with elevated levels of heme and iron, which induced ferroptosis. Here, we found Nrf2 knockout in SCD mice accumulated the levels of the metabolite L-2-hydroxyglutarate (L2HG), which impaired ferroptosis stress response to exacerbate SCD symptom. Mechanistically, L2HG was found to regulate the expression of genes involved in the iron and heme metabolism via histone epigenetic hypermethylation. Our findings indicate an important role of Nrf2/L2HG in SCD for ferroptosis response.

2021-11-19 | GSE188695 | GEO

Nrf2-regulated L-2-hydroxyglutarate sensitizes erythroid cells to ferroptosis in sickle cell disease [ChIP]

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Nrf2-regulated L-2-hydroxyglutarate sensitizes erythroid cells to ferroptosis in sickle cell disease [ChIP-seq]

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Nrf2-regulated L-2-hydroxyglutarate sensitizes erythroid cells to ferroptosis in sickle cell disease [ChIP]

Project description:Nrf2-regulated L-2-hydroxyglutarate sensitizes erythroid cells to ferroptosis in sickle cell disease [ChIP]

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Nrf2-regulated L-2-hydroxyglutarate sensitizes erythroid cells to ferroptosis in sickle cell disease [ChIP-seq]

Project description:Nrf2-regulated L-2-hydroxyglutarate sensitizes erythroid cells to ferroptosis in sickle cell disease [ChIP-seq]

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MFSD7C protects hemolysis-induced lung impairments by inhibiting ferroptosis

Project description:Hemolysis drives susceptibility to lung injury and predicts poor outcomes in diseases, such as malaria and sickle cell disease (SCD). However, the underlying pathological mechanism remains unknown. Here, we report that major facilitator superfamily domain containing 7C (MFSD7C) protects the lung from hemolytic-induced damage by preventing ferroptosis. Mechanistically, MFSD7C deficiency leads to mitochondrial dysfunction and lipid remodeling caused by increased fatty acid uptake and decreased consumption, the excess accumulation of lipids sensitizes cells to peroxidation and ferroptosis. Moreover, systematic delivery of MFSD7C mRNA-loaded nanoparticles to the lungs effectively prevented lung injury in mice with hemolysis. These findings present the detailed link between hemolytic complications and ferroptosis, providing potential therapeutic targets for patients with hemolytic disorders.

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MYCN mediates cysteine addiction and sensitizes to ferroptosis

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MYCN mediates cysteine addiction and sensitizes neuroblastoma to ferroptosis

Project description:MYCN mediates cysteine addiction and sensitizes neuroblastoma to ferroptosis

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CircPOLA2 sensitizes NSCLC cells to ferroptosis and suppresses tumorigenesis via the Merlin-YAP signaling pathway

Project description:Circular RNAs (circRNAs) have been implicated in the tumorigenesis of non-small cell lung cancer (NSCLC). Ferroptosis is considered a mechanism to suppress tumorigenesis. Herein, we identified a novel downregulated circRNA, circPOLA2 (hsa_circ_0004291), in NSCLC tissues and found that it was correlated with advanced clinical stage in patients. Nuclear-cytoplasmic fractionation assays and FISH assays confirmed that circPOLA2 was predominantly localized in the cytoplasm. Overexpression of circPOLA2 promoted lipid peroxidation and ferroptosis in NSCLC cells, thereby inhibiting cell proliferation and migration, while knockdown of circPOLA2 exerted the opposite effects. Mechanistically, circPOLA2 interacted with Merlin, a critical regulator of the Hippo pathway, and restricted Merlin phosphorylation at S518, leading to the activation of the Hippo pathway. In addition, circPOLA2 enhanced ferroptosis in NSCLC cells by activating the Hippo pathway. Together, circPOLA2 sensitizes cells to ferroptosis and suppresses tumorigenesis in NSCLC by facilitating Merlin-mediated activation of the Hippo signaling pathway.

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Project description:BRD4 inhibition sensitizes diffuse large B-cell lymphoma cells to ferroptosis

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