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Clinical and Translational Oncology

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18.09.2017 | Research Article

NFBD1/MDC1 participates in the regulation of proliferation and apoptosis in human laryngeal squamous cell carcinoma

verfasst von: X. Liu, Z. Qiu, Z. Wang, W. Zuo, Z. Gong, C. Liu, Q. Zeng, Y. Qian, L. Jiang, Y. Li, Y. Bu, G. Hu

Erschienen in: Clinical and Translational Oncology | Ausgabe 4/2018

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Abstract

Purpose

The objective of the study was to investigate the role of NFBD1 in the proliferation and apoptosis of laryngeal squamous cell carcinoma (LSCC) cells.

Methods

Immunohistochemistry (IHC) and qRT-PCR was employed to determine the expressions of NFBD1 protein and mRNA in LSCC tissues and adjacent noncancerous tissues. After the downregulation of NFBD1 expression, the colony formation assay, MTS assay and apoptosis assay were used to investigate the changes in the proliferation and apoptosis of Hep2 cells. The mechanisms by which silencing NFBD1 promote apoptosis of Hep2 cells were examined by western blotting. Furthermore, xenograft models were used to evaluate the proliferation of Hep2 cells in vivo.

Results

NFBD1 protein was upregulated in 55.6% of LSCC cancer tissues compared with adjacent normal tissues (26.7%). NFBD1 knockdown in Hep2 cells significantly impacted proliferation and apoptosis, and silencing NFBD1 might promote apoptosis of Hep2 cells by activating the mitochondrial apoptotic pathway. Xenograft models showed that silencing NFBD1 also significantly inhibited tumor growth.

Conclusions

Our data highlight that NFBD1 participates in the regulation of proliferation and apoptosis in LSCC, and suggest that NFBD1 could be a promising therapy target.

Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65(2):87–108. doi:10.3322/caac.21262.CrossRefPubMed

Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 2016;66(1):7–30. doi:10.3322/caac.21332.CrossRefPubMed

Tai P, Yu E, Shiels R, Tonita J. Long-term survival rates of laryngeal cancer patients treated by radiation and surgery, radiation alone, and surgery alone: studied by lognormal and Kaplan–Meier survival methods. BMC Cancer. 2005;5:13. doi:10.1186/1471-2407-5-13.CrossRefPubMedPubMedCentral

Varghese BT, Sebastian P, Mathew A. Treatment outcome in patients undergoing surgery for carcinoma larynx and hypopharynx: a follow-up study. Acta Otolaryngol. 2009;129(12):1480–5. doi:10.3109/00016480902748520.CrossRefPubMed

Yilmaz M, Karatas OF, Yuceturk B, Dag H, Yener M, Ozen M. Alpha-B-crystallin expression in human laryngeal squamous cell carcinoma tissues. Head Neck. 2015;37(9):1344–8. doi:10.1002/hed.23746.CrossRefPubMed

Cacicedo J, Fernandez I, del Hoyo O, Navarro A, Gomez-Iturriaga A, Pijoan JI, et al. Prognostic value of maximum standardized uptake value measured by pretreatment 18F-FDG PET/CT in locally advanced head and neck squamous cell carcinoma. Clin Transl Oncol. 2017;. doi:10.1007/s12094-017-1674-6.PubMed

Valenciano A, Henríquez-Hernández LA, Lloret M, Pinar B, Lara PC. New biological markers in the decision of treatment of head and neck cancer patients. Clin Transl Oncol. 2014;16(10):849–58. doi:10.1007/s12094-014-1193-7.CrossRefPubMed

Jeggo PA, Pearl LH, Carr AM. DNA repair, genome stability and cancer: a historical perspective. Nat Rev Cancer. 2016;16(1):35–42. doi:10.1038/nrc.2015.4.CrossRefPubMed

Ozaki T, Nagase T, Ichimiya S, Seki N, Ohiri M, Nomura N, et al. NFBD1/KIAA0170 is a novel nuclear transcriptional transactivator with BRCT domain. DNA Cell Biol. 2000;19(8):475–85. doi:10.1089/10445490050128403.CrossRefPubMed

10.

Goldberg M, Stucki M, Falck J, D’Amours D, Rahman D, Pappin D, et al. MDC1 is required for the intra-S-phase DNA damage checkpoint. Nature. 2003;421(6926):952–6.CrossRefPubMed

11.

Stewart GS, Wang B, Bignell CR, Taylor AMR, Elledge SJ. MDC1 is a mediator of the mammalian DNA damage checkpoint. Nature. 2003;421(6926):961–6.CrossRefPubMed

12.

Stiff T, O’Driscoll M, Rief N, Iwabuchi K, Lobrich M, Jeggo PA. ATM and DNA-PK function redundantly to phosphorylate H2AX after exposure to ionizing radiation. Cancer Res. 2004;64(7):2390–6.CrossRefPubMed

13.

Eliezer Y, Argaman L, Kornowski M, Roniger M, Goldberg M. Interplay between the DNA damage proteins MDC1 and ATM in the regulation of the spindle assembly checkpoint. J Biol Chem. 2014;289(12):8182–93. doi:10.1074/jbc.M113.532739.CrossRefPubMedPubMedCentral

14.

Lou Z, Minter-Dykhouse K, Wu X, Chen J. MDC1 is coupled to activated CHK2 in mammalian DNA damage response pathways. Nature. 2003;421(6926):957–61. doi:10.1038/nature01447.CrossRefPubMed

15.

Lou Z, Minter-Dykhouse K, Franco S, Gostissa M, Rivera MA, Celeste A, et al. MDC1 maintains genomic stability by participating in the amplification of ATM-dependent DNA damage signals. Mol Cell. 2006;21(2):187–200.CrossRefPubMed

16.

Nakanishi M, Ozaki T, Yamamoto H, Hanamoto T, Kikuchi H, Furuya K, et al. NFBD1/MDC1 associates with p53 and regulates its function at the crossroad between cell survival and death in response to DNA damage. J Biol Chem. 2007;282(31):22993–3004. doi:10.1074/jbc.M611412200.CrossRefPubMed

17.

Wang Z, Zeng Q, Chen T, Liao K, Bu Y, Hong S, et al. Silencing NFBD1/MDC1 enhances the radiosensitivity of human nasopharyngeal cancer CNE1 cells and results in tumor growth inhibition. Cell Death Dis. 2015;6:e1849. doi:10.1038/cddis.2015.214.CrossRefPubMedPubMedCentral

18.

Zeng Q, Wang Z, Liu C, Gong Z, Yang L, Jiang L, et al. Knockdown of NFBD1/MDC1 enhances chemosensitivity to cisplatin or 5-fluorouracil in nasopharyngeal carcinoma CNE1 cells. Mol Cell Biochem. 2016;418(1–2):137–46. doi:10.1007/s11010-016-2739-5.CrossRefPubMed

19.

Wang Z, Liao K, Zuo W, Liu X, Qiu Z, Gong Z, et al. Depletion of NFBD1/MDC1 induces apoptosis in nasopharyngeal carcinoma cells through the p53-ROS-mitochondrial pathway. Oncol Res. 2017;25(1):123–36. doi:10.3727/096504016x14732772150226.CrossRefPubMed

20.

Yuan C, Bu Y, Wang C, Yi F, Yang Z, Huang X, et al. NFBD1/MDC1 is a protein of oncogenic potential in human cervical cancer. Mol Cell Biochem. 2012;359(1):333.CrossRefPubMed

21.

Bartkova J, Horejsi Z, Sehested M, Nesland JM, Rajpert-De Meyts E, Skakkebaek NE, et al. DNA damage response mediators MDC1 and 53BP1: constitutive activation and aberrant loss in breast and lung cancer, but not in testicular germ cell tumours. Oncogene. 2007;26(53):7414–22. doi:10.1038/sj.onc.1210553.CrossRefPubMed

22.

Patel AN, Goyal S, Wu H, Schiff D, Moran MS, Haffty BG. Mediator of DNA damage checkpoint protein 1 (MDC1) expression as a prognostic marker for nodal recurrence in early-stage breast cancer patients treated with breast-conserving surgery and radiation therapy. Breast Cancer Res Treat. 2011;126(3):601–7. doi:10.1007/s10549-010-0960-6.CrossRefPubMed

23.

Wang Z, Liao K, Zuo W, Liu X, Qiu Z, Gong Z, et al. Depletion of NFBD1/MDC1 induces apoptosis in nasopharyngeal carcinoma cells through the p53-ROS-mitochondrial pathway. Oncol Res Featur Preclin Clin Cancer Ther. 2017;25(1):123–36. doi:10.3727/096504016X14732772150226.

24.

Li J, Huang CY, Zheng RL, Cui KR, Li JF. Hydrogen peroxide induces apoptosis in human hepatoma cells and alters cell redox status. Cell Biol Int. 2000;24(1):9–23. doi:10.1006/cbir.1999.0438.CrossRefPubMed

25.

Reuter S, Eifes S, Dicato M, Aggarwal BB, Diederich M. Modulation of anti-apoptotic and survival pathways by curcumin as a strategy to induce apoptosis in cancer cells. Biochem Pharmacol. 2008;76(11):1340–51. doi:10.1016/j.bcp.2008.07.031.CrossRefPubMed

26.

Balaban RS, Nemoto S, Finkel T. Mitochondria, oxidants, and aging. Cell. 2005;120(4):483–95. doi:10.1016/j.cell.2005.02.001.CrossRefPubMed

27.

Uo T, Kinoshita Y, Morrison RS. Apoptotic actions of p53 require transcriptional activation of PUMA and do not involve a direct mitochondrial/cytoplasmic site of action in postnatal cortical neurons. J Neurosci Off J Soc Neurosci. 2007;27(45):12198.CrossRef

28.

Zhao Y, Chaiswing L, Velez JM, Batinichaberle I, Colburn NH, Oberley TD, et al. p53 translocation to mitochondria precedes its nuclear translocation and targets mitochondrial oxidative defense protein-manganese superoxide dismutase. Can Res. 2005;65(9):3745–50.CrossRef

Titel: NFBD1/MDC1 participates in the regulation of proliferation and apoptosis in human laryngeal squamous cell carcinoma
verfasst von: X. Liu
Z. Qiu
Z. Wang
W. Zuo
Z. Gong
C. Liu
Q. Zeng
Y. Qian
L. Jiang
Y. Li
Y. Bu
G. Hu
Publikationsdatum: 18.09.2017
Verlag: Springer International Publishing
Erschienen in: Clinical and Translational Oncology / Ausgabe 4/2018
Print ISSN: 1699-048X
Elektronische ISSN: 1699-3055
DOI: https://doi.org/10.1007/s12094-017-1748-5

Springer Medizin

NFBD1/MDC1 participates in the regulation of proliferation and apoptosis in human laryngeal squamous cell carcinoma

Abstract

Purpose

Methods

Results

Conclusions

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Springer Medizin

Abstract

Purpose

Methods

Results

Conclusions

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