Expression and methylation of mitochondrial transcription factor a in chronic obstructive pulmonary disease patients with lung cancer

Hong Peng, Min Yang, Zhi Yong Chen, Ping Chen, Cha Xiang Guan, Xu Dong Xiang, Shan Cai, Yan Chen, Xiang Fang

Research output: Contribution to journalArticle

15 Citations (Scopus)

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). Conclusion: 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.

Original languageEnglish (US)
Article numbere82739
JournalPLoS One
Volume8
Issue number12
DOIs
StatePublished - Dec 18 2013

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Pulmonary diseases
Methylation
lung neoplasms
methylation
respiratory tract diseases
Chronic Obstructive Pulmonary Disease
Lung Neoplasms
Transcription Factors
transcription factors
Obstructive Lung Diseases
Squamous Cell Neoplasms
lungs
Proteins
Endothelial cells
Lung
Messenger RNA
blood vessels
proteins
endothelial cells
Endothelial Cells

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Expression and methylation of mitochondrial transcription factor a in chronic obstructive pulmonary disease patients with lung cancer. / Peng, Hong; Yang, Min; Chen, Zhi Yong; Chen, Ping; Guan, Cha Xiang; Xiang, Xu Dong; Cai, Shan; Chen, Yan; Fang, Xiang.

In: PLoS One, Vol. 8, No. 12, e82739, 18.12.2013.

Research output: Contribution to journalArticle

Peng, Hong ; Yang, Min ; Chen, Zhi Yong ; Chen, Ping ; Guan, Cha Xiang ; Xiang, Xu Dong ; Cai, Shan ; Chen, Yan ; Fang, Xiang. / Expression and methylation of mitochondrial transcription factor a in chronic obstructive pulmonary disease patients with lung cancer. In: PLoS One. 2013 ; Vol. 8, No. 12.
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AU - Yang, Min

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AU - Guan, Cha Xiang

AU - Xiang, Xu Dong

AU - Cai, Shan

AU - Chen, Yan

AU - Fang, Xiang

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N2 - 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). Conclusion: 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.

AB - 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). Conclusion: 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.

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