Mitochondrial DNA 4977-bp deletion correlated with reactive oxygen species production and manganese superoxide dismutase expression in gastric tumor cells
Open accessAbstract
BACKGROUND: Mitochondrial DNA 4977-bp deletion (DeltamtDNA(4977)) was reported in many human neoplasia. However, its biological significance remains to be evaluated and the molecular mechanism needs to be investigated. In this study, we analyzed the frequency of DeltamtDNA(4977) in gastric cancer (GC) cell lines and tissues, as well as reactive oxygen species (ROS) contents and manganese superoxide dismutase (MnSOD) expression levels in GC cell lines to explore its biological significance and molecular mechanism. METHODS: Semi-quantitative PCR and real-time PCR were used to detect the incidence of DeltamtDNA(4977) in 13 GC cell lines and 272 human gastric tissues (108 GC specimens and the respective adjacent normal tissues, and 56 normal gastric mucosa from non-cancer patients). We further identified intracellular ROS production by flow cytometry and MnSOD expression by semi-quantitative reverse transcription-PCR (RT-PCR) and Western blotting. Statistical analyses were carried out using the Logistic regression analysis and Kaplan-Meier method. RESULTS: Based on our earlier study, we optimized the PCR amplification condition by reducing the cycle number. In this study, we systematically documented the high incidence of DeltamtDNA(4977) in GC cell lines (10/13, 76.9%), GC tissues (86/108, 79.6%), matched normal tissues (73/108, 67.6%), and normal gastric mucosa of non-cancer patients (29/56, 51.8%). A significantly higher incidence of mutated DeltamtDNA(4977) was observed in GC tissues with respect to the adjacent normal tissues (79.6% vs 67.6%, P = 0.045), and they were both higher than that in normal controls (P < 0.05). Most importantly, we linked the DeltamtDNA(4977) mutations with the expression level of MnSOD and ROS contents. The cell lines containing lower expression level of MnSOD was found to have generally higher frequent DeltamtDNA(4977) and more ROS. CONCLUSION: The decreased anti-oxidative ability, which leads to increased ROS contents, is correlated with the mtDNA damage during gastric carcinogenesis.
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Cells with high levels of the common deletion produce more reactive oxygen species when stimulated with an H2O2 insult, resulting in reduced cell viability.
“the cells with high levels of this common deletion produce more reactive oxygen species when stimulated with an H2O2 insult, resulting in reduced cell viability (Jou et al., 2005; Liu et al., 2007; Wang and Lu, 2009).”
From Mitochondrial dysfunction and pathology in bipolar disorder and schizophrenia (2011) · cites this paper as Wang and Lu, 2009
Cites
Superoxide radical and superoxide dismutases
Fridovich, I. (1995) · Annual Review of Biochemistry · doi:10.1146/annurev.bi.64.070195.000525 · Cited by 3,455 · see citing works
Biology of disease: free radicals and tissue injury.
Freeman, B. Α., & Jd, C. (1982) · PubMed · Cited by 3,059 · see citing works
The cellular production of hydrogen peroxide
Boveris, A., Oshino, N., & Chance, B. (1972) · Biochemical Journal · doi:10.1042/bj1280617 · Cited by 1,549 · see citing works
ROS-Generating Mitochondrial DNA Mutations Can Regulate Tumor Cell Metastasis
Ishikawa, K., Takenaga, K., Akimoto, M., Koshikawa, N., Yamaguchi, A., Imanishi, H., Nakada, K., Honma, Y., & Hayashi, J.-I. (2008) · Science · doi:10.1126/science.1156906 · Cited by 1,444 · see citing works
mtDNA mutations increase tumorigenicity in prostate cancer
Petros, J. A., Baumann, A. K., Ruiz‐Pesini, E., Amin, M. B., Sun, C. Q., Hall, J., Lim, S.-D., Issa, M. M., Flanders, W. D., Hosseini, S. H., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0408894102 · Cited by 834 · see citing works
Mitochondrial DNA sequence variation in human evolution and disease.
Wallace, D. C. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.19.8739 · Cited by 520 · see citing works
Chomyn, A., Martinuzzi, A., Yoneda, M., Daga, A., Hurko, O., Johns, D. R., Lai, S. T., Nonaka, I., Angelini, C. I., & Attardi, G. M. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.10.4221 · Cited by 491 · see citing works
Ambrosone, C. B., Freudenheim, J. L., Thompson, P. A., Bowman, E. D., Vena, J. E., Marshall, J. R., Graham, S., Laughlin, R., Nemoto, T., & Shields, P. G. (1999) · PubMed · Cited by 400 · see citing works
Pitkanen, S., & Robinson, B. H. (1996) · Journal of Clinical Investigation · doi:10.1172/jci118798 · Cited by 388 · see citing works
Hirose, K., Longo, D. L., Oppenheim, J. J., & Matsushima, K. (1993) · The FASEB Journal · doi:10.1096/fasebj.7.2.8440412 · Cited by 340 · see citing works
Mitochondrial DNA repair and aging
Mandavilli, B. S., Santos, J. H., & Houten, B. V. (2002) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/s0027-5107(02)00220-8 · Cited by 338 · see citing works
Wispé, J. R., Warner, B. B., Clark, J. C., Dey, C. R., Neuman, J. T., Glasser, S. W., Crapo, J. D., Chang, L. Y., & Whitsett, J. A. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)35927-1 · Cited by 314 · see citing works
Sciacco, M., Bonilla, E., Schon, E. A., DiMauro, S., & Moraes, C. T. (1994) · Human Molecular Genetics · doi:10.1093/hmg/3.1.13 · Cited by 305 · see citing works
Regulation of reactive oxygen species-induced apoptosis and necrosis by caspase 3-like proteases
Higuchi, M., Honda, T., Proske, R. J., & Yeh, E. T. H. (1998) · Oncogene · doi:10.1038/sj.onc.1202211 · Cited by 223 · see citing works
Oberley, T. D. (2002) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)64857-2 · Cited by 201 · see citing works
Mitochondrial genome instability in human cancers
Bianchi, N. O., Bianchi, M. S., & Richard, S. M. (2001) · Mutation Research/Reviews in Mutation Research · doi:10.1016/s1383-5742(00)00063-6 · Cited by 189 · see citing works
Two direct repeats cause most human mtDNA deletions
Samuels, D. C., Schon, E. A., & Chinnery, P. F. (2004) · Trends in Genetics · doi:10.1016/j.tig.2004.07.003 · Cited by 185 · see citing works
Mitochondrial Dysfunction Is a Common Phenotype in Aging and Cancer
Singh, K. K. (2004) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1297.043 · Cited by 104 · see citing works
Yen, T., King, K.-L., Lee, H.-C., et al. (1994) · Free Radical Biology & Medicine · doi:10.1016/0891-5849(94)90145-7 · Cited by 96 · see citing works
Urano, M., Kuroda, M., Reynolds, R., et al. (1995) · PubMed · Cited by 71 · see citing works
Large deletions in mitochondrial DNA in radiation-associated human thyroid tumors.
Rogounovitch, T., Saenko, V., Shimizu‐Yoshida, Y., Abrosimov, A. Y., Lushnikov, E. F., Roumiantsev, P. O., Ohtsuru, A., Namba, H., Tsyb, A. F., & Yamashita, S. (2002) · PubMed · Cited by 61 · see citing works
Dani, M. A. C., Dani, S. U., Lima, S. P. G., et al. (2004) · PubMed · Cited by 52 · see citing works
Deng, G. R., Lu, Y. Y., Chen, S. M., et al. (1987) · PubMed · Cited by 46 · see citing works
Shieh, D., Chou, W. P., Wei, Y., et al. (2004) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1293.016 · Cited by 33 · see citing works
ΔmtDNA4977 Is More Common in Non-tumoral Cells from Gastric Cancer Sample
Kamalıdehghan, B., Houshmand, M., Ismail, P., et al. (2006) · Archives of Medical Research · doi:10.1016/j.arcmed.2006.02.005 · Cited by 24 · see citing works
Dani, S. U., Dani, M. A. C., & Simpson, A. J. G. (2003) · Medical Hypotheses · doi:10.1016/s0306-9877(03)00105-1 · Cited by 19 · see citing works
Shen, H., Zhao, M., Dong, B., et al. (2003) · PubMed · Cited by 6 · see citing works
Frequent mtDNA mutations and its role in gastric carcinogenesis
Liu, M., & Lu, Y. (2002) · Chinese Science Bulletin · doi:10.1007/bf03183316 · Cited by 2 · see citing works
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Mitochondrial dysfunction and pathology in bipolar disorder and schizophrenia
Clay, H. B., Daws, S., & Konradi, C. (2011) · International Journal of Developmental Neuroscience · doi:10.1016/j.ijdevneu.2010.08.007 · Cited by 399 · see citing works
- Authors
- WANG, J., & LÜ, Y.-Y.
- Affiliations
- Peking University Cancer Hospital (CN)
- ORCID
- WANG, Juan
- Venue
- Chinese Medical Journal
- Published
- 2009-02
- Volume
- 122
- Issue
- 4
- Pages
- 431-436
- ISSN
- 0366-6999 (ISSN-L)
- OpenAlex
- W1458950882
- Cited by
- 33
- References
- 28
- Citations by year
- 2025: 1 · 2022: 1 · 2021: 4 · 2020: 2 · 2019: 2 · 2018: 1 · 2017: 1 · 2015: 3 · 2014: 3 · 2013: 5 · 2012: 4
- FWCI
- 1.34
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by-nc-nd
- Locations
- Chinese Medical Journal (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer and biochemical research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Keywords
- 4977 bp deletion, gastric cancer, reactive oxygen species, manganese superoxide dismutase, oxidative stress, gastric carcinogenesis, mitochondrial DNA damage, gastric cancer cell lines
- MeSH terms
- Adult, Aged, Aged, 80 and over, DNA, Mitochondrial, Female, Humans, Male, Middle Aged, Mutation, Stomach Neoplasms, Superoxide Dismutase, Blotting, Western, Reactive Oxygen Species, Reverse Transcriptase Polymerase Chain Reaction, Cell Line, Tumor, In Vitro Techniques
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