title: Expression and methylation of mitochondrial transcription factor a in chronic obstructive pulmonary disease patients with lung cancer.
abstract: BACKGROUND
  Apoptosis plays a central role in the pathogenesis of chronic obstructive pulmonary disease (COPD), and this process can be regulated by mitochondrial transcription factor A (mtTFA). Epigenetics is involved in the regulation and modification of the genes involved in lung cancer and COPD. In this study, we determined the expression of mtTFA and its methylation levels in the COPD patients with lung cancer.
  
  
  METHODS
  Twenty-one squamous cell lung cancer patients, 11 with COPD and 10 without COPD, undergoing pneumonectomy were enrolled. The apoptotic index (AI) of pulmonary vascular endothelial cells was analyzed by transferase-mediated deoxyuridine triphosphate-biotin nick end labeling assay. The expression of mtTFA mRNA and protein was measured using PCR, immunohistochemistry and Western-blot. Methylation of the mtTFA promoter was detected using bisulfite sequencing PCR.
  
  
  RESULTS
  Compared to the non-COPD group, the AI was higher, and expression of mtTFA mRNA and protein was lower in the COPD group (P<0.001). Expression of the mtTFA protein was positively correlated with FEV1/Pre (r = 0.892, P<0.001), and negatively correlated with AI (r = -0.749, P<0.001) and smoke index (r = -0.763, P<0.001). Percentage of mtTFA promoter methylation in the COPD patients was significantly higher compared to the non-COPD patients (P<0.05).
  
  
  CONCLUSIONS
  These results suggest that the expression of mtTFA mRNA and protein is down-regulated in the lung tissue from the COPD patients with squamous cell lung cancer, and the level of mtTFA protein is related to apoptosis of pulmonary vascular endothelial cells. Aberrant mtTFA methylation may also play an important role in the pathogenesis of COPD.
authors.affiliation: Department of Respiratory Medicine, The Second Xiangya Hospital of Central-South University, Changsha, Hunan, PR China.
authors.forename: Hong
authors.initials: H
authors.lastname: Peng
authors.affiliation: Department of Respiratory Medicine, The Second Xiangya Hospital of Central-South University, Changsha, Hunan, PR China ; Human Key Laboratory of Medical Epigenomics, The Second Xiangya Hospital of Central-South University, Changsha, Hunan, PR China.
authors.forename: Min
authors.initials: M
authors.lastname: Yang
authors.affiliation: Department of Urology, Xiangya Hospital of Central-South University, Changsha, Hunan, PR China.
authors.forename: Zhi-yong
authors.initials: ZY
authors.lastname: Chen
authors.affiliation: Department of Respiratory Medicine, The Second Xiangya Hospital of Central-South University, Changsha, Hunan, PR China.
authors.forename: Ping
authors.initials: P
authors.lastname: Chen
authors.affiliation: Physiological Research Center, Xiangya Medical School of Central-South University, Changsha, Hunan, PR China.
authors.forename: Cha-xiang
authors.initials: CX
authors.lastname: Guan
authors.affiliation: Department of Respiratory Medicine, The Second Xiangya Hospital of Central-South University, Changsha, Hunan, PR China.
authors.forename: Xu-dong
authors.initials: XD
authors.lastname: Xiang
authors.affiliation: Department of Respiratory Medicine, The Second Xiangya Hospital of Central-South University, Changsha, Hunan, PR China.
authors.forename: Shan
authors.initials: S
authors.lastname: Cai
authors.affiliation: Department of Respiratory Medicine, The Second Xiangya Hospital of Central-South University, Changsha, Hunan, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Neurology, University of Texas Medical Branch, Galveston, Texas, United States of America.
authors.forename: Xiang
authors.initials: X
authors.lastname: Fang
mesh_terms: D000328:Adult; D019175:DNA Methylation / Q000235:genetics* / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D006801:Humans; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000235:genetics* / Q000378:metabolism*; D029424:Pulmonary Disease, Chronic Obstructive / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; C422562:mitochondrial transcription factor A