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NFBD1/MDC1 is a protein of oncogenic potential in human cervical cancer

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Abstract

A large nuclear protein of 2089 amino acids, NFBD1/MDC1 has recently been implicated in tumorigenesis and tumor growth. In this study, we investigated its expression in cervical cancers and explored its function using gene knockdown approaches. We report here that NFBD1 expression is substantial increased in 24 of 39 cases (61.5%) of cervical cancer tissues at the mRNA level and in 35 of 60 cases (58.3%) at the protein level compared with the case matched normal tissues. Tumors with higher grade of malignancy tend to have higher levels of NFBD1 expression. By infecting cells with retroviruses expressing NFBD1 shRNA, we successfully knocked down NFBD1 expression in cervical cancer cell lines HeLa, SiHa, and CaSki. NFBD1 knockdown cells display significant growth inhibition, cell cycle arrest, higher apoptotic rate, and enhanced sensitivity to adriamycin. Furthermore, NFBD1 knockdown also inhibits the growth of HeLa cells in nude mice. Western blot analyses further revealed that NFBD1 knockdown induced Bax, Puma, and Noxa while down-regulating Bcl-2; it also up-regulated cytochrome C and activated caspases 3 and 9. Therefore, the function of NFBD1 may be involved in the CDC25C–CyclinB1/CDC2 pathway at the G2/M checkpoint, and the cytochrome C/caspase 3 apoptotic pathway. Since expression of NFBD1 seems to be related to the oncogenic potential of cervical cancer, and suppression of its expression can inhibit cancer cell growth both in vitro and in vivo, NFBD1 may be a potential therapeutic target in human cervical cancer.

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Acknowledgments

This work was supported by grants from National Natural Science Foundation of China (No. 30872758, No. 30800410, and No. 30871237).

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All the authors declare no conflicts of interest.

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Authors and Affiliations

  1. Department of Biochemistry & Molecular Biology, Molecular Medicine & Cancer Research Center, Chongqing Medical University, Chongqing, 400016, People’s Republic of China

    Chengfu Yuan, Youquan Bu, Changdong Wang, Faping Yi, Xiuning Huang, Li Cheng, Geli Liu, Yong Wang & Fangzhou Song

  2. Laboratory Animal Center, Chongqing Medical University, Chongqing, 400016, People’s Republic of China

    Zhengmei Yang

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  1. Chengfu Yuan
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  2. Youquan Bu
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  3. Changdong Wang
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  4. Faping Yi
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  5. Zhengmei Yang
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  6. Xiuning Huang
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  7. Li Cheng
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  8. Geli Liu
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  9. Yong Wang
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  10. Fangzhou Song
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Correspondence to Fangzhou Song.

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Yuan, C., Bu, Y., Wang, C. et al. NFBD1/MDC1 is a protein of oncogenic potential in human cervical cancer. Mol Cell Biochem 359, 333–346 (2012). https://doi.org/10.1007/s11010-011-1027-7

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  • DOI: https://doi.org/10.1007/s11010-011-1027-7

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