• Users Online: 67
  • Print this page
  • Email this page
ORIGINAL ARTICLE
Year : 2020  |  Volume : 53  |  Issue : 5  |  Page : 165-176

Role of mitochondrial DNA copy number alteration in non-small cell lung cancer


1 Center for General Education, Kainan University, Taoyuan City; School of Life Science, National Taiwan Normal University; Faculty of Medicine, National Yang-Ming University, Taipei; Division of Thoracic Surgery, Taipei Hospital, Ministry of Health and Welfare, New Taipei City, Taiwan
2 Faculty of Medicine, National Yang-Ming University; Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
3 Center for Mitochondrial Medicine and Free Radical Research, Changhua Christian Hospital, Changhua City, Taiwan
4 Division of Thoracic Surgery, Taipei Hospital, Ministry of Health and Welfare, New Taipei City; Department of Life Science and Institute of Genome Sciences, National Yang-Ming University, Taipei, Taiwan
5 Department of Life Science and Institute of Genome Sciences, National Yang-Ming University, Taipei, Taiwan
6 Division of Pathology, Feng-Yuan Hospital, Ministry of Health and Welfare, Taichung City, Taiwan

Correspondence Address:
Chen-Sung Lin
Taipei Hospital, Ministry of Health and Welfare, New Taipei City
Taiwan
Yau-Huei Wei
Center for Mitochondrial Medicine and Free Radical Research, Changhua Christian Hospital, Changhua City
Taiwan
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/fjs.fjs_15_20

Rights and Permissions

Background: Mitochondrial dysfunction may involve in the progression of human non-small cell lung cancers (NSCLCs). We analyzed the mitochondrial DNA (mtDNA) copy number, the expression levels of mitochondrial biogenesis-related proteins including pyruvate dehydrogenase, mitochondrial transcription factor A (TFAM) and mtDNA-encoded peptide NADH dehydrogenase subunit 1 (ND1), and the expression level of hexokinase II (HK-II) in human NSCLCs both ex vivo and in vitro. Materials and Methods: Paired cancerous and non-cancerous pathological specimens from 20 resected NSCLCs and an NSCLC cell line, the H23, were used in this study. H23 was infected by lentiviral particles to knockdown (KD) the expression of TFAM. TFAM-Null and TFAM-KD represent the control and TFAM knocked-down H23 cells, respectively. The mtDNA copy number was measured by quantitative real-time polymerase chain reaction and the protein expression levels were measured by immunohistochemical staining and Western blotting, respectively. Results: Low TFAM expression (P = 0.066) and low mtDNA copy number of NSCLCs (P = 0.009) were poor prognostic variables in NSCLC patients. Advanced T4 NSCLCs had lower TFAM expression (P = 0.021), lower expression of mtDNA-encoded ND1 polypeptide (P = 0.049), and lower mtDNA copy number (P = 0.050) than did T1 or T2/T3 NSCLCs, respectively. TFAM-KD cells expressed lower levels of TFAM protein (P < 0.005), ND1 polypeptide (P < 0.005) and mtDNA copy number (P = 0.003), but higher level of vimentin protein (P = 0.045) and higher transwell migration activity (P = 0.003) than did TFAM-Null cells. Conclusion: Mitochondrial dysfunction caused by lower levels of TFAM, mtDNA copy number, and mtDNA-encoded ND1 polypeptide may play an important role in the progression of NSCLCs.


[FULL TEXT] [PDF]*
Print this article     Email this article
 Next article
 Previous article
 Table of Contents

 Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
 Citation Manager
 Access Statistics
 Reader Comments
 Email Alert *
 Add to My List *
 * Requires registration (Free)
 

 Article Access Statistics
    Viewed492    
    Printed4    
    Emailed0    
    PDF Downloaded54    
    Comments [Add]    

Recommend this journal