Journal article
Alteration of mitochondrial biogenesis promotes disease progression in multiple myeloma
Oncotarget, Vol.8(67), pp.111213-111224
2017
DOI: 10.18632/oncotarget.22740
PMCID: PMC5762316
PMID: 29340048
Abstract
Many cancers, including multiple myeloma (MM), retain more cytosolic iron to promote tumor cell growth and drug resistance. Higher cytosolic iron promotes oxidative damage due to its interaction with reactive oxygen species generated by mitochondria. The variation of mitochondrial biogenesis in different stages of MM disease was evaluated using gene expression profiles in a large clinical dataset. Sixteen of 18mitochondrial biogenesis related gene sets, including mitochondrial biogenesis signature and oxidative phosphorylation, were increased in myeloma cells compared with normal plasma cells and high expression was associated with an inferior patient outcome. Relapsed and drug resistant myeloma samples had higher expression of mitochondrial biogenesis signatures than newly diagnosed patient samples. The expression of mitochondrial biogenesis genes was regulated by the cellular iron content, which showed a synergistic effect in patient outcome in MM. Pharmacological ascorbic acid induced myeloma cell death by inhibition of mitochondria oxidative phosphorylation in an
in vivo
model. Here, we identify that dysregulated mitochondrial biogenesis and iron homeostasis play a major role in myeloma progression and patient outcome and that pharmacological ascorbic acid, through cellular iron content and mitochondrial oxidative species, should be considered as a novel treatment in myeloma including drug-resistant and relapsed patients.
Details
- Title: Subtitle
- Alteration of mitochondrial biogenesis promotes disease progression in multiple myeloma
- Creators
- Xin Zhan - University of IowaWenjie Yu - Department of Anatomy and Cell Biology University of Iowa, Iowa City, IA, USAReinaldo Franqui-Machin - Molecular & Cellular Biology Program, University of Iowa, Iowa City, IA, USAMelissa L Bates - Department of Health and Human Physiology, University of Iowa, Iowa City, IA, USAKalyan Nadiminti - Division of Hematology, Oncology, and Blood and Marrow Transplantation, Department of Internal Medicine, University of Iowa, Iowa City, IA, USAHuojun Cao - Department of Endodontics University of Iowa, Iowa City, IA, USABrad A Amendt - Department of Endodontics University of Iowa, Iowa City, IA, USAYogesh Jethava - Division of Hematology, Oncology, and Blood and Marrow Transplantation, Department of Internal Medicine, University of Iowa, Iowa City, IA, USAIvana Frech - Division of Hematology, Oncology, and Blood and Marrow Transplantation, Department of Internal Medicine, University of Iowa, Iowa City, IA, USAFenghuang Zhan - Division of Hematology, Oncology, and Blood and Marrow Transplantation, Department of Internal Medicine, University of Iowa, Iowa City, IA, USAGuido Tricot - Division of Hematology, Oncology, and Blood and Marrow Transplantation, Department of Internal Medicine, University of Iowa, Iowa City, IA, USA
- Resource Type
- Journal article
- Publication Details
- Oncotarget, Vol.8(67), pp.111213-111224
- DOI
- 10.18632/oncotarget.22740
- PMID
- 29340048
- PMCID
- PMC5762316
- NLM abbreviation
- Oncotarget
- ISSN
- 1949-2553
- eISSN
- 1949-2553
- Publisher
- Impact Journals LLC
- Language
- English
- Date published
- 2017
- Academic Unit
- Orthodontics; Anatomy and Cell Biology; Endodontics; Stead Family Department of Pediatrics; Surgery; Craniofacial Anomalies Research Center; Dental Research; Health, Sport, and Human Physiology ; Internal Medicine
- Record Identifier
- 9984002473302771
Metrics
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