Expression and methylation of mitochondrial transcription factor a in chronic obstructive pulmonary disease patients with lung cancer.
<h4>Background</h4>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 lu...
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oai:doaj.org-article:dfe6fa40a96744c0ae61c9961bafaf042021-11-18T08:41:21ZExpression and methylation of mitochondrial transcription factor a in chronic obstructive pulmonary disease patients with lung cancer.1932-620310.1371/journal.pone.0082739https://doaj.org/article/dfe6fa40a96744c0ae61c9961bafaf042013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24367550/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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).<h4>Conclusion</h4>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.Hong PengMin YangZhi-yong ChenPing ChenCha-xiang GuanXu-dong XiangShan CaiYan ChenXiang FangPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 12, p e82739 (2013) |
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Medicine R Science Q Hong Peng Min Yang Zhi-yong Chen Ping Chen Cha-xiang Guan Xu-dong Xiang Shan Cai Yan Chen Xiang Fang Expression and methylation of mitochondrial transcription factor a in chronic obstructive pulmonary disease patients with lung cancer. |
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<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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).<h4>Conclusion</h4>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. |
format |
article |
author |
Hong Peng Min Yang Zhi-yong Chen Ping Chen Cha-xiang Guan Xu-dong Xiang Shan Cai Yan Chen Xiang Fang |
author_facet |
Hong Peng Min Yang Zhi-yong Chen Ping Chen Cha-xiang Guan Xu-dong Xiang Shan Cai Yan Chen Xiang Fang |
author_sort |
Hong Peng |
title |
Expression and methylation of mitochondrial transcription factor a in chronic obstructive pulmonary disease patients with lung cancer. |
title_short |
Expression and methylation of mitochondrial transcription factor a in chronic obstructive pulmonary disease patients with lung cancer. |
title_full |
Expression and methylation of mitochondrial transcription factor a in chronic obstructive pulmonary disease patients with lung cancer. |
title_fullStr |
Expression and methylation of mitochondrial transcription factor a in chronic obstructive pulmonary disease patients with lung cancer. |
title_full_unstemmed |
Expression and methylation of mitochondrial transcription factor a in chronic obstructive pulmonary disease patients with lung cancer. |
title_sort |
expression and methylation of mitochondrial transcription factor a in chronic obstructive pulmonary disease patients with lung cancer. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2013 |
url |
https://doaj.org/article/dfe6fa40a96744c0ae61c9961bafaf04 |
work_keys_str_mv |
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