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High Expression of BCCIP β Can Promote Proliferation of Esophageal Squamous Cell Carcinoma

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Abstract

Background

BCCIP was originally identified as a BRCA2 interacting protein in humans and Ustilago maydis. It had low expression in some human cancer tissues. However, recent research indicated that many caretaker genes are also necessary for cell viability and their expression could contribute to tumor progression.

Aim

To characterize whether BCCIP is a caretaker gene in esophageal squamous cell carcinoma (ESCC).

Methods

Western blotting and immunohistochemistry were used to measure the expression of BCCIP β. In vitro studies were used to verify the effects of BCCIP β in Eca109 cells.

Results

Expression of BCCIP β was notably higher in tumor tissues of ESCC and Eca 109 cells. Meanwhile, the immunohistochemistry stain revealed that BCCIP β was positively correlated with clinical pathologic variables such as tumor size and tumor grade, as well as Ki-67, and prompted poor prognosis. In vitro studies such as starvation and refeeding assay along with BCCIP β-shRNA transfection assay demonstrated that BCCIP β expression promoted proliferation of ESCC cells. In addition, BCCIP β downregulation by silencing RNA significantly decreased the rate of colony formation, alleviated cellular apoptosis and increased the chemosensitivity of cisplatin.

Conclusions

This research first put forward that BCCIP β is an oncogene in human ESCC and contributes to the poor outcome of the deadly disease.

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References

  1. Rustgi AK, El-Serag HB. Esophageal carcinoma. N Engl J Med. 2014;371:2499–2509.

    Article  PubMed  Google Scholar 

  2. Orringer MB, Marshall B, Iannettoni MD. Transhiatal esophagectomy: clinical experience and refinements. Ann Surg. 1999;230:392–400. (discussion 393–400).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Liu J, Yuan Y, Huan J, Shen Z. Inhibition of breast and brain cancer cell growth by BCCIPalpha, an evolutionarily conserved nuclear protein that interacts with BRCA2. Oncogene. 2001;20:336–345.

    Article  CAS  PubMed  Google Scholar 

  4. Ono T, Kitaura H, Ugai H, et al. TOK-1, a novel p21Cip1-binding protein that cooperativ-ely enhances p21-dependent inhibitory activity toward CDK2 kinase. J Biol Chem. 2000;275:31145–31154.

    Article  CAS  PubMed  Google Scholar 

  5. Lu H, Guo X, Meng X, et al. The BRCA2-interacting protein BCCIP functions in RAD51 and BRCA2 focus formation and homologous recombinational repair. Mol Cell Biol. 2005;25:1949–1957.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Meng X, Liu J, Shen Z. Genomic structure of the human BCCIP gene and its expression in cancer. Gene. 2003;302:139–146.

    Article  CAS  PubMed  Google Scholar 

  7. Fan J, Wray J, Meng X, Shen Z. BCCIP is required for the nuclear localization of the p21 protein. Cell Cycle. 2009;8:3019–3024.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Liu X, Cao L, Ni J, et al. Differential BCCIP gene expression in primary human ovarian cancer, renal cell carcinoma and colorectal cancer tissues. Int J Oncol. 2013;43:1925–1934.

    CAS  PubMed  Google Scholar 

  9. Roversi G, Pfundt R, Moroni RF, et al. Identification of novel genomic markers related to progression to glioblastoma through genomic profiling of 25 primary glioma cell lines. Oncogene. 2006;25:1571–1583.

    Article  CAS  PubMed  Google Scholar 

  10. Meng X, Liu J, Shen Z. Inhibition of G1 to S cell cycle progression by BCCIP beta. Cell Cycle. 2004;3:343–348.

    CAS  PubMed  Google Scholar 

  11. Meng X, Lu H, Shen Z. BCCIP functions through p53 to regulate the expression of p21Waf1/Cip1. Cell Cycle. 2004;3:1457–1462.

    Article  CAS  PubMed  Google Scholar 

  12. Lu H, Yue J, Meng X, Nickoloff JA, Shen Z. BCCIP regulates homologous recombination by distinct domains and suppresses spontaneous DNA damage. Nucleic Acids Res. 2007;35:7160–7170.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Meng X, Fan J, Shen Z. Roles of BCCIP in chromosome stability and cytokinesis. Oncogene. 2007;26:6253–6260.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Lu H, Huang YY, Mehrotra S, et al. Essential roles of BCCIP in mouse embryonic development and structural stability of chromosomes. PLoS Genet. 2011;7:e1002291.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Huang YY, Dai L, Gaines D, et al. BCCIP suppresses tumor initiation but is required for tumor progression. Cancer Res. 2013;73:7122–7133.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Wang Y, Yang S, Ni Q, et al. Overexpression of forkhead box J2 can decrease the migration of breast cancer cells. J Cell Biochem. 2012;113:2729–2737.

    Article  CAS  PubMed  Google Scholar 

  17. Zhang J, Yang X, Wang Y, et al. Low expression of cyclinH and cyclin-dependent kinase 7 can decrease the proliferation of human esophageal squamous cell carcinoma. Dig Dis Sci. 2013;58:2028–2037.

    Article  CAS  PubMed  Google Scholar 

  18. Wang Y, Wang Y, Xiang J, et al. Knockdown of CRM1 inhibits the nuclear export of p27(Kip1) phosphorylated at serine 10 and plays a role in the pathogenesis of epithelial ovarian cancer. Cancer Lett. 2014;343:6–13.

    Article  CAS  PubMed  Google Scholar 

  19. Alvarez V, Vinas L, Gallego-Sanchez A, Andres S, Sacristan MP, Bueno A. Orderly progression through S-phase requires dynamic ubiquitylation and deubiquitylation of PCNA. Sci Rep. 2016;6:25513.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Liu J, Lu H, Ohgaki H, Merlo A, Shen Z. Alterations of BCCIP, a BRCA2 interacting protein, in astrocytomas. BMC Cancer. 2009;9:268.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Rewari A, Lu H, Parikh R, Yang Q, Shen Z, Haffty BG. BCCIP as a prognostic marker for radiotherapy of laryngeal cancer. Radiother Oncol. 2009;90:183–188.

    Article  CAS  PubMed  Google Scholar 

  22. Meng X, Yue J, Liu Z, Shen Z. Abrogation of the transactivation activity of p53 by BCCIP down-regulation. J Biol Chem. 2007;282:1570–1576.

    Article  CAS  PubMed  Google Scholar 

  23. Huang YY, Lu H, Liu S, Droz-Rosario R, Shen Z. Requirement of mouse BCCIP for neural development and progenitor proliferation. PLoS ONE. 2012;7:e30638.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Mao N, Zhou Q, Kojic M, Perez-Martin J, Holloman WK. Ortholog of BRCA2-interacting protein BCCIP controls morphogenetic responses during DNA replication stress in Ustilago maydis. DNA Repair. 2007;6:1651–1660.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Audhya A, Emr SD. Regulation of PI4,5P2 synthesis by nuclear-cytoplasmic shuttling of the Mss4 lipid kinase. EMBO J. 2003;22:4223–4236.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Wyler E, Wandrey F, Badertscher L, Montellese C, Alper D, Kutay U. The beta-isoform of the BRCA2 and CDKN1A(p21)-interacting protein (BCCIP) stabilizes nuclear RPL23/uL14. FEBS Lett. 2014;588:3685–3691.

    Article  CAS  PubMed  Google Scholar 

  27. Kinzler KW, Vogelstein B. Cancer-susceptibility genes. Gatekeepers and caretakers. Nature. 1997;386:761–763.

    Article  CAS  PubMed  Google Scholar 

  28. Zheng Y, Stamminger T, Hearing P. E2F/Rb family proteins mediate interferon induced repression of adenovirus immediate early transcription to promote persistent viral infection. PLoS Pathog. 2016;12:e1005415.

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This work was supported by Grants from the National Natural Science Foundation of China (Nos. 81171140, 81472272).

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Correspondence to Runzhou Ni or Jianguo Zhang.

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Conflict of interest

The authors declare no competing financial interest.

Additional information

Lingling Chen and Sujie Ni have contributed equally to this work.

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Fig. S1

BCCIP expression in ESCC tissues. Seven paired samples of ESCC tumor tissues (T) and adjacent non-tumor tissues (N). This figure with the primary data suggests that BCCIP α expression is not as evident as in BCCIP β and is even silenced in tumor tissues (TIFF 1157 kb)

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Chen, L., Ni, S., Li, M. et al. High Expression of BCCIP β Can Promote Proliferation of Esophageal Squamous Cell Carcinoma. Dig Dis Sci 62, 387–395 (2017). https://doi.org/10.1007/s10620-016-4382-0

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  • DOI: https://doi.org/10.1007/s10620-016-4382-0

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