NFBD1/MDC1 participates in the regulation of proliferation and apoptosis in human laryngeal squamous cell carcinoma
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The objective of the study was to investigate the role of NFBD1 in the proliferation and apoptosis of laryngeal squamous cell carcinoma (LSCC) cells.
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.
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.
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.
KeywordsLaryngeal squamous cell carcinoma (LSCC) NFBD1/MDC1 Apoptosis Cell cycle
This work was financed from the funds of the National Natural Science Foundation of China (81470676 and 81271061).
Compliance with ethical standards
Conflict of interest
All the authors declare no conflict of interest.
All protocols using animals were approved by the Institutional Animal Care and Use Committee of Chongqing Medical University. All procedures performed in studies involving human participants were in accordance with the ethical standards of the Human Ethics Committee of the First Affiliated Hospital of Chongqing Medical University and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
- 3.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.CrossRefPubMedPubMedCentralGoogle Scholar
- 6.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.PubMedGoogle Scholar
- 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.CrossRefPubMedGoogle Scholar
- 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.CrossRefPubMedGoogle Scholar
- 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.CrossRefPubMedGoogle Scholar