title: The influence of mtDNA deletion on lung cancer cells under the conditions of hypoxia and irradiation.
abstract: OBJECTIVE
  This study was to evaluate the influence of mtDNA deletion on the lung cancer cells under the conditions of hypoxia or irradiation.
  
  
  METHODS
  The treatment conditions of lung cancer cell lines with (A549) and without mtDNA (ρ0A549: obtained by inducing from A549) included 2 h of hypoxia and 4 Gy irradiation (group 1: without treatment; group 2: 2 h of hypoxia; group 3: 4 Gy irradiation; group 4: 2 h of hypoxia plus 4 Gy irradiation). The Human OneArray™ microarray was used to hybridize with the Cy5-labeled aRNA in microarray sample preparation. Differentially expressed genes (DEGs) between the lung cancer cells with and without mtDNA were identified using NOISeq package in R. Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed using the online tool of DAVID.
  
  
  RESULTS
  In the KEGG pathway analysis of down-regulated DEGs, nineteen pathways were simultaneously enriched in the four groups, which were mainly metabolism- and biosynthesis-related pathways. Nine lung cancer-related pathways were enriched in group 4, and more cancer-associated DEGs, such as MYC, MAX, and E2F1 were found in group 4 than in the other groups.
  
  
  CONCLUSIONS
  The mtDNA deletion could inhibit the biosynthesis and metabolism of lung cancer cells and promote the effect of hypoxia and radiation on lung cancer cells. MYC might be the key gene of the cooperation of hypoxia and radiation and MYC, MAX, and E2F1 might play roles in hypoxia- and radiation-induced cell death in lung cancer cells without mtDNA.
authors.affiliation: Department of Oncology, Shengjing Hospital of China Medical University, No.39 Huaxiang Road, Tiexi District, Shenyang, 110022, China, hancb@126.com.
authors.forename: Cheng-Bo
authors.initials: CB
authors.lastname: Han
authors.forename: Li
authors.initials: L
authors.lastname: Sun
authors.forename: Jie-Tao
authors.initials: JT
authors.lastname: Ma
authors.forename: Yao-Yong
authors.initials: YY
authors.lastname: Li
authors.forename: Shu-Ling
authors.initials: SL
authors.lastname: Zhang
authors.forename: Dong-Mei
authors.initials: DM
authors.lastname: Bai
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhou
authors.forename: Le-Tian
authors.initials: LT
authors.lastname: Huang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D016022:Case-Control Studies; D016923:Cell Death / Q000235:genetics; D045744:Cell Line, Tumor / Q000528:radiation effects*; D004272:DNA, Mitochondrial / Q000235:genetics*; D015536:Down-Regulation; D017353:Gene Deletion; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D000860:Hypoxia; D008175:Lung Neoplasms / Q000235:genetics / Q000503:physiopathology; D046228:Microarray Analysis; D011829:Radiation Dosage; D011839:Radiation, Ionizing; D012016:Reference Values; D012680:Sensitivity and Specificity; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D004272:DNA, Mitochondrial; C114022:MYCBP2 protein, human; D044767:Ubiquitin-Protein Ligases