
DOI . ORG {
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Title[redir]:
Targeting ERRα promotes cytotoxic effects against acute myeloid leukemia through suppressing mitochondrial oxidative phosphorylation | Journal of Hematology & Oncology | Full Text
Description:
Acute myeloid leukemia (AML) is an aggressive blood cancer with poor clinical outcomes. Emerging data suggest that mitochondrial oxidative phosphorylation (mtOXPHOS) plays a significant role in AML tumorigenesis, progression, and resistance to chemotherapies. However, how the mtOXPHOS is regulated in AML cells is not well understood. In this study, we investigated the oncogenic functions of ERRα in AML by combining in silico, in vitro, and in vivo analyses and showed ERRα is a key regulator of mtOXPHOS in AML cells. The increased ERRα level was associated with worse clinical outcomes of AML patients. Single cell RNA-Seq analysis of human primary AML cells indicated that ERRα-expressing cancer cells had significantly higher mtOXPHOS enrichment scores. Blockade of ERRα by pharmacologic inhibitor (XCT-790) or gene silencing suppressed mtOXPHOS and increased anti-leukemic effects in vitro and in xenograft mouse models.
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Keywords {🔍}
errα, cells, aml, fig, additional, cell, file, data, article, genes, korea, mtoxphos, xct, expression, significantly, myeloid, target, treatment, google, scholar, information, leukemia, patients, mitochondrial, authors, medicine, analysis, acute, kim, cancer, aneuploid, experiments, national, south, higher, lines, kgα, mice, cas, research, university, oxidative, lee, jun, survival, receptor, expressed, pathway, test, control,
Topics {✒️}
estrogen-related receptor alpha estrogen-related receptor-α springer nature jin-man kim hee-seon choi mitochondrial oxidative phosphorylation eun-kyeong jo jun young heo supplementary figures min joung lee specific pathogen-free environment errα-expressing cancer cells errα-expressing malignant cells data represent means ± sd sang-hee lee lymphoid-primed multipotent progenitor aml patient-derived cells patient-derived aml cells increased anti-leukemic effects jae-young lee ik-chan song oxidative phosphorylation privacy choices/manage cookies kyeong tae kim nod/scid mice acute myeloid leukemia shns-kg1α-engrafted mice xct-790-treated cells independent soo-yeon woo authors scientific editing korea research institute bmc sherrα-kg1α-engrafted mice nod/scid/il2rγnull state privacy rights full size image single-cell level additional information publisher' abbreviations aml rna-seq data require oxidative metabolism acute myeloid leukaemia information related sang min jeon pusan national university myeloid leukemia cells dongjun lee venn diagram showing availability sharing
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headline:Targeting ERRα promotes cytotoxic effects against acute myeloid leukemia through suppressing mitochondrial oxidative phosphorylation
description:Acute myeloid leukemia (AML) is an aggressive blood cancer with poor clinical outcomes. Emerging data suggest that mitochondrial oxidative phosphorylation (mtOXPHOS) plays a significant role in AML tumorigenesis, progression, and resistance to chemotherapies. However, how the mtOXPHOS is regulated in AML cells is not well understood. In this study, we investigated the oncogenic functions of ERRα in AML by combining in silico, in vitro, and in vivo analyses and showed ERRα is a key regulator of mtOXPHOS in AML cells. The increased ERRα level was associated with worse clinical outcomes of AML patients. Single cell RNA-Seq analysis of human primary AML cells indicated that ERRα-expressing cancer cells had significantly higher mtOXPHOS enrichment scores. Blockade of ERRα by pharmacologic inhibitor (XCT-790) or gene silencing suppressed mtOXPHOS and increased anti-leukemic effects in vitro and in xenograft mouse models.
datePublished:2022-10-26T00:00:00Z
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ERRα
Mitochondrial oxidative phosphorylation
Apoptosis
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Hematology
Cancer Research
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headline:Targeting ERRα promotes cytotoxic effects against acute myeloid leukemia through suppressing mitochondrial oxidative phosphorylation
description:Acute myeloid leukemia (AML) is an aggressive blood cancer with poor clinical outcomes. Emerging data suggest that mitochondrial oxidative phosphorylation (mtOXPHOS) plays a significant role in AML tumorigenesis, progression, and resistance to chemotherapies. However, how the mtOXPHOS is regulated in AML cells is not well understood. In this study, we investigated the oncogenic functions of ERRα in AML by combining in silico, in vitro, and in vivo analyses and showed ERRα is a key regulator of mtOXPHOS in AML cells. The increased ERRα level was associated with worse clinical outcomes of AML patients. Single cell RNA-Seq analysis of human primary AML cells indicated that ERRα-expressing cancer cells had significantly higher mtOXPHOS enrichment scores. Blockade of ERRα by pharmacologic inhibitor (XCT-790) or gene silencing suppressed mtOXPHOS and increased anti-leukemic effects in vitro and in xenograft mouse models.
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ERRα
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Cancer Research
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address:
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type:PostalAddress
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address:
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type:PostalAddress
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address:
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type:PostalAddress
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type:PostalAddress
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affiliation:
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address:
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type:PostalAddress
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affiliation:
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type:PostalAddress
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name:Sema4, Stamford, USA
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name:Center for Research Equipment, Korea Basic Science Institute, Cheongju, South Korea
name:Department of Convergence Medicine, School of Medicine, Pusan National University, Yangsan, South Korea
name:Department of Convergence Medicine, School of Medicine, Pusan National University, Yangsan, South Korea
name:Biotechnology Process Engineering Center, Korea Research Institute of Bioscience and Biotechnology, Cheongju, South Korea
name:Department of Medical Science and Infection Control Convergence Research Center, Chungnam National University College of Medicine, Daejeon, South Korea
name:Infection Control Convergence Research Center, Chungnam National University College of Medicine, Daejeon, South Korea
name:Department of Medical Science and Infection Control Convergence Research Center, Chungnam National University College of Medicine, Daejeon, South Korea
name:Infection Control Convergence Research Center, Chungnam National University College of Medicine, Daejeon, South Korea
name:Department of Medical Science and Infection Control Convergence Research Center, Chungnam National University College of Medicine, Daejeon, South Korea
name:Infection Control Convergence Research Center, Chungnam National University College of Medicine, Daejeon, South Korea
name:Department of Medical Science and Infection Control Convergence Research Center, Chungnam National University College of Medicine, Daejeon, South Korea
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name:Infection Control Convergence Research Center, Chungnam National University College of Medicine, Daejeon, South Korea
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