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Mitochondrial DNA in Lung Cancer

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Mitochondrial DNA and Diseases

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1038))

Abstract

Mitochondrial DNA (mtDNA) variations are increasingly discovered and expected to be potential biomarkers to monitor severity, duration, stage, response to therapy, and prognosis in patients with lung cancer. The present article illustrates alterations of mtDNA in lung cancer, including alterations of mtDNA copy number and sequence mutations, as well as their possible mechanisms for carcinogenesis and development of lung cancer. The clear and comprehensive relationships between mtDNA variations and lung cancer are to be further confirmed to benefit effective strategies for lung cancer diagnosis and therapy.

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References

  1. Ding C, Li R, Wang P, Jin P, Li S, Guo Z. Identification of sequence polymorphisms in the D-loop region of mitochondrial DNA as a risk factor for lung cancer. Mitochondrial DNA. 2012;23:251–4. PMID:22708867

    Article  CAS  PubMed  Google Scholar 

  2. Hsu H-C, Li S-J, Chen C-Y, Chen M-F. Eicosapentaenoic acid protects cardiomyoblasts from lipotoxicity in an autophagy-dependent manner. Cell Biol Toxicol. 2017:1–13. PMID:28741157

    Google Scholar 

  3. Kazdal D, Harms A, Endris V, Penzel R, Kriegsmann M, Eichhorn F, Muley T, Stenzinger A, Pfarr N, Weichert W. Prevalence of somatic mitochondrial mutations and spatial distribution of mitochondria in non-small cell lung cancer. Br J Cancer. 2017.; PMID:28557978

    Google Scholar 

  4. Fliss MS, Usadel H, Caballero OL, Wu L, Buta MR, Eleff SM, Jen J, Sidransky D. Facile detection of mitochondrial DNA mutations in tumors and bodily fluids. Science. 2000;287:2017–9. PMID:10720328

    Article  CAS  PubMed  Google Scholar 

  5. Richard SM, Bailliet G, Páez GL, Bianchi MS, Peltomäki P, Bianchi NO. Nuclear and mitochondrial genome instability in human breast cancer. Cancer Res. 2000;60:4231–7. PMID:10945635

    CAS  PubMed  Google Scholar 

  6. Witte J, Lehmann S, Wulfert M, Yang Q, Röher HD. Mitochondrial DNA mutations in differentiated thyroid cancer with respect to the age factor. World J Surg. 2007;31:51–9. PMID:17171498

    Article  PubMed  Google Scholar 

  7. Yuan Y, Wang W, Li H, Yu Y, Tao J, Huang S, Zeng Z. Nonsense and missense mutation of mitochondrial ND6 gene promotes cell migration and invasion in human lung adenocarcinoma. BMC Cancer. 2015;15:346. PMID:25934296

    Article  PubMed  PubMed Central  Google Scholar 

  8. Pagani IS, Kok CH, Saunders VA, Van der Hoek MB, Heatley SL, Schwarer AP, Hahn CN, Hughes TP, White DL, Ross DMA. Method for next-generation sequencing of paired diagnostic and remission samples to detect mitochondrial DNA mutations associated with leukemia. J Mol Diagn. 2017.; PMID:28732215

    Google Scholar 

  9. Bao L, Zhang Y, Wang J, Wang H, Dong N, Su X, Xu M, Wang X. Variations of chromosome 2 gene expressions among patients with lung cancer or non-cancer. Cell Biol Toxicol. 2016;32:419–35. PMID:27301951

    Article  CAS  PubMed  Google Scholar 

  10. Bao L, Diao H, Dong N, Su X, Wang B, Mo Q, Yu H, Wang X, Chen C. Histone deacetylase inhibitor induces cell apoptosis and cycle arrest in lung cancer cells via mitochondrial injury and p53 up-acetylation. Cell Biol Toxicol. 2016;32:469–82. PMID:27423454

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Fang X, Netzer M, Baumgartner C, Bai C, Wang X. Genetic network and gene set enrichment analysis to identify biomarkers related to cigarette smoking and lung cancer. Cancer Treat Rev. 2013;39:77–88. PMID:22789435

    Article  CAS  PubMed  Google Scholar 

  12. Anderson S, Bankier AT, Barrell BG, de Bruijn MH, Coulson AR, Drouin J, Eperon IC, Nierlich DP, Roe BA, Sanger F. Sequence and organization of the human mitochondrial genome. Nature. 1981;290:457–65. PMID:7219534

    Article  CAS  PubMed  Google Scholar 

  13. Medvedev R, Hildt E, Ploen D. Look who’s talking—the crosstalk between oxidative stress and autophagy supports exosomal-dependent release of HCV particles. Cell Biol Toxicol. 2017:1–21. PMID:27987184

    Google Scholar 

  14. Kang D, Hamasaki N. Mitochondrial oxidative stress and mitochondrial DNA. Clin Chem Lab Med. 2003;41:1281–8. PMID:14580153

    Article  CAS  PubMed  Google Scholar 

  15. Zhu L-Z, Hou Y-J, Zhao M, Yang M-F, Fu X-T, Sun J-Y, Fu X-Y, Shao L-R, Zhang H-F, Fan C-D. Caudatin induces caspase-dependent apoptosis in human glioma cells with involvement of mitochondrial dysfunction and reactive oxygen species generation. Cell Biol Toxicol. 2016;32:333–45. PMID:27184666

    Article  CAS  PubMed  Google Scholar 

  16. Yeh JJ, Lunetta KL, van Orsouw NJ, Jr MF, Mutter GL, Vijg J, Dahia PL, Eng C. Somatic mitochondrial DNA (mtDNA) mutations in papillary thyroid carcinomas and differential mtDNA sequence variants in cases with thyroid tumours. Oncogene. 2000;19:2060–6. PMID:10803467

    Article  CAS  PubMed  Google Scholar 

  17. Morais R, Desjardins P, Turmel C, Zinkewichpéotti K. Development and characterization of continuous avian cell lines depleted of mitochondrial DNA. Vitro Cell & Dev Biol J Tissue Cult Assoc. 1988;24:649–58. PMID:2840430

    Article  CAS  Google Scholar 

  18. Suzuki M, Toyooka S, Miyajima K, Iizasa T, Fujisawa T, Bekele NB, Gazdar AF. Alterations in the mitochondrial displacement loop in lung cancers. Clin Cancer Res. 2003;9:5636–41. PMID:14654546

    CAS  PubMed  Google Scholar 

  19. Kim W-H, Shen H, Jung D-W, Williams DR. Some leopards can change their spots: potential repositioning of stem cell reprogramming compounds as anti-cancer agents. Cell Biol Toxicol. 2016;32:157–68. PMID:27156576

    Article  PubMed  Google Scholar 

  20. Nishikawa M, Nishiguchi S, Shiomi S, Tamori A, Koh N, Takeda T, Kubo S, Hirohashi K, Kinoshita H, Sato E. Somatic mutation of mitochondrial DNA in cancerous and noncancerous liver tissue in individuals with hepatocellular carcinoma. Cancer Res. 2001;61:1843–5. PMID:11280735

    CAS  PubMed  Google Scholar 

  21. Chatterjee A, Mambo E, Sidransky D. Mitochondrial DNA mutations in human cancer. Oncogene. 2006;25:4663–74. PMID:16892080

    Article  CAS  PubMed  Google Scholar 

  22. Wallace DC. Mitochondrial diseases in man and mouse. Science. 1999;283:1482–8. PMID:10066162

    Article  CAS  PubMed  Google Scholar 

  23. Khansari N, Shakiba Y, Mahmoudi M. Chronic inflammation and oxidative stress as a major cause of age- related diseases and cancer. Recent Patents Inflamm Allergy Drug Discov. 2009;3:73–80. PMID:19149749

    Article  CAS  Google Scholar 

  24. Pelicano H, Carney D, Huang P. ROS stress in cancer cells and therapeutic implications. Drug Resist Updat. 2004;7:97–110. PMID:15158766

    Article  CAS  PubMed  Google Scholar 

  25. Brandon M, Baldi P, Wallace DC. Mitochondrial mutations in cancer. Oncogene. 2006;25:4647–62. PMID:16892079

    Article  CAS  PubMed  Google Scholar 

  26. Kulawiec M, Owens KM, Singh KK. Cancer cell mitochondria confer apoptosis resistance and promote metastasis. Cancer Biol Ther. 2014;8:1378–85. PMID:19556849

    Article  Google Scholar 

  27. Iii HDH, Liu CS, Rothman N, Weinstein SJ, Bonner MR, Shen M, Lim U, Virtamo J, Cheng W, Albanes D. Mitochondrial DNA copy number and lung cancer risk in a prospective cohort study. Carcinogenesis. 2010;31:847–9. PMID:20176654

    Article  Google Scholar 

  28. Mizumachi T, Muskhelishvili L, Naito A, Furusawa J, Fan CY, Siegel ER, Kadlubar FF, Kumar U, Higuchi M. Increased distributional variance of mitochondrial DNA content associated with prostate cancer cells as compared with normal prostate cells. Prostate. 2008;68:408–17. PMID:18196528

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Jiang WW, Masayesva B, Zahurak M, Carvalho AL, Rosenbaum E, Mambo E, Zhou S, Minhas K, Benoit N, Westra WH. Increased mitochondrial DNA content in saliva associated with head and neck cancer. Clin Cancer Res. 2005;11:2486–91. PMID: 15814624

    Article  CAS  PubMed  Google Scholar 

  30. Ellinger J, Albers P, Müller SC, Von RA, Bastian PJ. Circulating mitochondrial DNA in the serum of patients with testicular germ cell cancer as a novel noninvasive diagnostic biomarker. BJU Int. 2009;104:48–52. PMID:19154496

    Article  CAS  PubMed  Google Scholar 

  31. Fan AX, Radpour R, Haghighi MM, Kohler C, Xia P, Hahn S, Holzgreve W, Zhong XY. Mitochondrial DNA content in paired normal and cancerous breast tissue samples from patients with breast cancer. J Cancer Res Clin. 2009;135:983–9. PMID:19125299

    Article  CAS  Google Scholar 

  32. Datta S, Majumder M, Biswas NK, Sikdar N, Roy B. Increased risk of oral cancer in relation to common Indian mitochondrial polymorphisms and autosomal GSTP1 locus. Cancer. 2007;110:1991–9. PMID:17886251

    Article  CAS  PubMed  Google Scholar 

  33. Malik AN, Czajka A. Is mitochondrial DNA content a potential biomarker of mitochondrial dysfunction? Mitochondrion. 2013;13:481–92. PMID:23085537

    Article  CAS  PubMed  Google Scholar 

  34. Lee HC, Li SH, Lin JC, CC W, Yeh DC, Wei YH. Somatic mutations in the D-loop and decrease in the copy number of mitochondrial DNA in human hepatocellular carcinoma. Mutat Res. 2004;547:71–8. PMID:15013701

    Article  CAS  PubMed  Google Scholar 

  35. Wang Y, Liu VWS, Xue WC, Cheung ANY, Ngan HYS. Association of decreased mitochondrial DNA content with ovarian cancer progression. Br J Cancer. 2006;95:1087–91. PMID:17047655

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Xu H, He W, Jiang HG, Zhao H, Peng XH, Wei YH, Wei JN, Xie CH, Liang C, Zhong YH. Prognostic value of mitochondrial DNA content and G10398A polymorphism in non-small cell lung cancer. Oncol Rep. 2013;30:3006–12. PMID:24101028

    Article  CAS  PubMed  Google Scholar 

  37. Wang H, Dai J. Changes on mitochondrial DNA content in non-small cell lung cancer. Chin J Lung Cancer. 2011;14:141. PMID:21342645

    CAS  Google Scholar 

  38. Lee HC, CY L, Fahn HJ, Wei YH. Aging- and smoking-associated alteration in the relative content of mitochondrial DNA in human lung. FEBS Lett. 1998;441:292. PMID:9883902

    Article  CAS  PubMed  Google Scholar 

  39. Turner CJ, Granycome C, Hurst R, Pohler E, Juhola MK, Juhola MI, Jacobs HT, Sutherland L, Holt IJ. Systematic segregation to mutant mitochondrial DNA and accompanying loss of mitochondrial DNA in human NT2 teratocarcinoma cybrids. Genetics. 2005;170:1879–85. PMID:15944344

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Singh KK, Sigala B, Sikder HA, Schwimmer C. Inactivation of Saccharomyces cerevisiae OGG1 DNA repair gene leads to an increased frequency of mitochondrial mutants. Nucleic Acids Res. 2001;29:1381–8. PMID:11239005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Zhang D, Mott JL, Chang SW, Denniger G, Feng Z, Zassenhaus HP. Construction of transgenic mice with tissue-specific acceleration of mitochondrial DNA mutagenesis. Genomics. 2000;69:151–61. PMID:11031098

    Article  CAS  PubMed  Google Scholar 

  42. Higuchi M. Regulation of mitochondrial DNA content and cancer. Mitochondrion. 2007;7:53–7. PMID:17320491

    Article  CAS  PubMed  Google Scholar 

  43. Sánchez AB, González-Sistal A. Novel role of p53 in maintaining mitochondrial genetic stability through interaction with DNA Pol γ. EMBO J. 2005;24:3482–92. PMID:16163384

    Article  Google Scholar 

  44. Isaacs C, Cavalli LR, Cohen Y, Pennanen M, Shankar LK, Freedman M, Singh B, Liu M, Gallagher A, Rone JD. Detection of LOH and mitochondrial DNA alterations in ductal lavage and nipple aspirate fluids from high-risk patients. Breast Cancer Res Treat. 2004;84:99–105. PMID:14999140

    Article  CAS  PubMed  Google Scholar 

  45. Bandy B, Davison AJ. Mitochondrial mutations may increase oxidative stress: implications for carcinogenesis and aging? Free Radic Biol Med. 1990;8:523–39. PMID:2193852

    Article  CAS  PubMed  Google Scholar 

  46. Shay JW, Werbin H. Are mitochondrial DNA mutations involved in the carcinogenic process? Mutat Res. 1987;186:149–60. PMID:3306359

    Article  CAS  PubMed  Google Scholar 

  47. Chiu RW, Chan LY, Lam NY, Tsui NB, Ng EK, Rainer TH, Lo YM. Quantitative analysis of circulating mitochondrial DNA in plasma. Clin Chem. 2003;49:719–26. PMID:12709361

    Article  CAS  PubMed  Google Scholar 

  48. Sui G, Zhou S, Wang J, Canto M, Lee EE, Eshleman JR, Montgomery EA, Sidransky D, Califano JA, Maitra A. Mitochondrial DNA mutations in preneoplastic lesions of the gastrointestinal tract: a biomarker for the early detection of cancer. Mol Cancer. 2006;5:73. PMID:17166268

    Article  PubMed  PubMed Central  Google Scholar 

  49. Wang X. New biomarkers and therapeutics can be discovered during COPD-lung cancer. Transition. 2016.; PMID:27405768

    Google Scholar 

  50. Gu J, Wang X. New future of cell biology and toxicology: thinking deeper. 2016; PMID:26874518

    Google Scholar 

  51. Wang X. CBT profiles of cabozantinib approved for advanced renal cell carcinomas. Cell Biol Toxicol. 2016;32:259–61. PMID:27383755

    Article  CAS  PubMed  Google Scholar 

  52. Chen C, Shi L, Li Y, Wang X, Yang S. Disease-specific dynamic biomarkers selected by integrating inflammatory mediators with clinical informatics in ARDS patients with severe pneumonia. Cell Biol Toxicol. 2016;32:169–84. PMID:27095254

    Article  PubMed  PubMed Central  Google Scholar 

  53. Shi L, Zhu B, Xu M, Wang X. Selection of AECOPD-specific immunomodulatory biomarkers by integrating genomics and proteomics with clinical informatics. Cell Biol Toxicol. 2017:1–15. PMID:28779230

    Google Scholar 

  54. Arumugam P, Samson A, Ki J, Song JM. Knockdown of clusterin alters mitochondrial dynamics, facilitates necrosis in camptothecin-induced cancer stem cells. Cell Biol Toxicol. 2017;33:307–21. PMID:28064403

    Article  CAS  PubMed  Google Scholar 

  55. Mossoba ME, Flynn TJ, Vohra S, Wiesenfeld PL, Sprando RL. Human kidney proximal tubule cells are vulnerable to the effects of Rauwolfia serpentina. Cell Biol Toxicol. 2015;31:285–93. PMID:26838987

    Article  CAS  PubMed  Google Scholar 

  56. Wu Y, Geng X-C, Wang J-F, Miao Y-F, Lu Y-L, Li B. The HepaRG cell line, a superior in vitro model to L-02, HepG2 and hiHeps cell lines for assessing drug-induced liver injury. Cell Biol Toxicol. 2016;32:37–59. PMID:27027780

    Article  CAS  PubMed  Google Scholar 

  57. Fathi H, Ebrahimzadeh MA, Ziar A, Mohammadi H. Oxidative damage induced by retching; antiemetic and neuroprotective role of Sambucus ebulus L. Cell Biol Toxicol. 2015;31:231–9. PMID:26493312

    Article  PubMed  Google Scholar 

  58. Zhu D, Liu Z, Pan Z, Qian M, Wang L, Zhu T, Xue Y, Wu D. A new method for classifying different phenotypes of kidney transplantation. Cell Biol Toxicol. 2016;32:323–32. PMID:27278387

    Article  CAS  PubMed  Google Scholar 

  59. Kikuchi S, Ninomiya T, Kohno T, Kojima T, Tatsumi H. Cobalt inhibits motility of axonal mitochondria and induces axonal degeneration in cultured dorsal root ganglion cells of rat. Cell Biol Toxicol. 2017:1–15. PMID:28656345

    Google Scholar 

  60. Kaarniranta K, Tokarz P, Koskela A, Paterno J, Blasiak J. Autophagy regulates death of retinal pigment epithelium cells in age-related macular degeneration. Cell Biol Toxicol. 2017:1–16. PMID:27900566

    Google Scholar 

  61. Chiang H-C, Wang C-H, Yeh S-C, Lin Y-H, Kuo Y-T, Liao C-W, Tsai F-Y, Lin W-Y, Chuang W-H, Tsou T-C. Comparative microarray analyses of mono (2-ethylhexyl) phthalate impacts on fat cell bioenergetics and adipokine network. Cell Biol Toxicol. 2017:1–16. PMID:28083810

    Google Scholar 

  62. Sanyal S, Das P, Law S. Effect of chronic pesticide exposure on murine cornea: a histopathological, cytological and flow cytometric approach to study ocular damage by xenobiotics. Cell Biol Toxicol. 2016;32:7–22. PMID:26897134

    Article  CAS  PubMed  Google Scholar 

  63. Soltani B, Ghaemi N, Sadeghizadeh M, Najafi F. Curcumin confers protection to irradiated THP-1 cells while its nanoformulation sensitizes these cells via apoptosis induction. Cell Biol Toxicol. 2016;32:543–61. PMID:27473378

    Article  CAS  PubMed  Google Scholar 

  64. Keta O, Bulat T, Golić I, Incerti S, Korać A, Petrović I, Ristić-Fira A. The impact of autophagy on cell death modalities in CRL-5876 lung adenocarcinoma cells after their exposure to γ-rays and/or erlotinib. Cell Biol Toxicol. 2016;32:83–101. PMID:27026538

    Article  CAS  PubMed  Google Scholar 

  65. Ganta KK, Mandal A, Chaubey B. Depolarization of mitochondrial membrane potential is the initial event in non-nucleoside reverse transcriptase inhibitor efavirenz induced cytotoxicity. Cell Biol Toxicol. 2017;33:69–82. PMID:27639578

    Article  PubMed  Google Scholar 

  66. Giromini C, Rebucci R, Fusi E, Rossi L, Saccone F, Baldi A. Cytotoxicity, apoptosis, DNA damage and methylation in mammary and kidney epithelial cell lines exposed to Ochratoxin A. Cell Biol Toxicol. 2016;32:249–58. PMID:27184667

    Article  CAS  PubMed  Google Scholar 

  67. Tlotleng N, Vetten MA, Keter FK, Skepu A, Tshikhudo R, Gulumian M. Cytotoxicity, intracellular localization and exocytosis of citrate capped and PEG functionalized gold nanoparticles in human hepatocyte and kidney cells. Cell Biol Toxicol. 2016;32:305–21. PMID:27184667

    Article  CAS  PubMed  Google Scholar 

  68. Divolis G, Mavroeidi P, Mavrofrydi O, Papazafiri P. Differential effects of calcium on PI3K-Akt and HIF-1α survival pathways. Cell Biol Toxicol. 2016;32:437–49. PMID:27344565

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

The work was supported by Zhongshan Distinguished Professor Grant (XDW), the National Nature Science Foundation of China (91230204, 81270099, 81320108001, 81270131, 81300010), the Shanghai Committee of Science and Technology (12JC1402200, 12431900207, 11410708600, 14431905100), Operation funding of Shanghai Institute of Clinical Bioinformatics, Ministry of Education for Academic Special Science and Research Foundation for PhD Education (20130071110043), and National Key Research and Development Program (2016YFC0902400, 2017YFSF090207).

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Authors and Affiliations

  1. Zhongshan Hospital Clinical Science Institute, Fudan University, Shanghai, China

    Fangming Liu

  2. Department of Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Freiburg im Breisgau, Germany

    David E. Sanin

  3. Zhongshan Hospital Institute of Clinical Science, Fudan University, Shanghai Medical College, Shanghai, China

    Xiangdong Wang

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  1. Fangming Liu
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  2. David E. Sanin
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  3. Xiangdong Wang
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Correspondence to Xiangdong Wang .

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Editors and Affiliations

  1. Liaoning Province Key Laboratory of Cancer Metabolomics, Jinzhou Hospital of Jinzhou Medical University, Jinzhou, Liaoning, China

    Hongzhi Sun

  2. Zhongshan Hospital Institute of Clinical Science, Fudan University, Shanghai Medical College, Shanghai, China

    Xiangdong Wang

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Liu, F., Sanin, D.E., Wang, X. (2017). Mitochondrial DNA in Lung Cancer. In: Sun, H., Wang, X. (eds) Mitochondrial DNA and Diseases. Advances in Experimental Medicine and Biology, vol 1038. Springer, Singapore. https://doi.org/10.1007/978-981-10-6674-0_2

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