title: Mitochondrial DNA Deficiency in Ovarian Cancer Cells and Cancer Stem Cell-like Properties.
abstract: BACKGROUND
  A low quantity of mitochondrial DNA (mtDNA) is a risk factor in a variety of tumor types. However, it is unclear how mtDNA reduction influences tumor behavior.
  
  
  METHODS
  mtDNA-deficient ovarian cancer cells were established by ethidium bromide (EtBr) treatment with additive combination of pyruvate and uridine.
  
  
  RESULTS
  The mtDNA-deficient cells had a low growth and colony-forming efficiency compared to the control cells. RNA sequencing revealed down-regulation of mitochondrion-related genes and up-regulation of genes related to cell proliferation and anti-apoptosis. The expression of genes involved in cancer metastasis, proliferation, angiogenesis, drug resistance and cancer cell stemness were also up-regulated. Intriguingly, cancer stem cell markers CD90 and CD117 were both up-regulated by EtBr dose-dependently in both cell lines.
  
  
  CONCLUSIONS
  MtDNA deficiency may induce ovarian cancer stem cell-like properties through different ways in vitro, therefore contributing to different tumor behaviors.
authors.affiliation: Department of Pathology, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway Department of Pathology, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
authors.forename: Ruixia
authors.initials: R
authors.lastname: Huang
authors.affiliation: Department of Pathology, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
authors.forename: Junbai
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, P.R. China.
authors.forename: Yali
authors.initials: Y
authors.lastname: Zhong
authors.affiliation: Biotherapy Center, the General Hospital of Beijing Military Command, Beijing, P.R. China.
authors.forename: Yishan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Radiation Biology-Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
authors.forename: Trond
authors.initials: T
authors.lastname: Stokke
authors.affiliation: Department of Gynaecology, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway Department of Gynaecology, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
authors.forename: Claes G
authors.initials: CG
authors.lastname: Trope
authors.affiliation: Department of Pathology, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway Department of Pathology, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
authors.forename: Jahn M
authors.initials: JM
authors.lastname: Nesland
authors.affiliation: Department of Pathology, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway Department of Pathology, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway zhenhes@medisin.uio.no.
authors.forename: Zhenhe
authors.initials: Z
authors.lastname: Suo
mesh_terms: D017209:Apoptosis / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D004272:DNA, Mitochondrial / Q000235:genetics*; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D006801:Humans; D008928:Mitochondria / Q000235:genetics; D014411:Neoplastic Stem Cells / Q000473:pathology*; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000473:pathology; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology*; D015854:Up-Regulation / Q000235:genetics
chemical_list: D004272:DNA, Mitochondrial
keywords: CSCs; Mitochondrion; RT-PCR; anti-apoptosis; cancer cell proliferation; cancer stem cells; immunocytochemistry; mitochondrial DNA deficiency/dysfunction; stemness; transcriptome sequencing/RNA deep-sequencing; western blotting