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Role of the functional variant (−652T>G) in the XRCC4 promoter in prostate cancer

Molecular Biology Reports volume 41, pages 7463–7470 (2014)Cite this article

Abstract

Several genes encoding DNA repair molecules have been proposed as cancer-susceptibility genes. Many studies have suggested that SNPs in XRCC4 could be implicated in altering the risk of prostate cancer (PCa). We examined the role of the functional variant (−652T>G) in the XRCC4 promoter in PCa. The transcriptional activity of XRCC4 gene was measured by luciferase assay. We performed real-time PCR/immunohistochemical assay to verify the association between expression level of XRCC4 mRNA/protein and XRCC4 −652T>G polymorphism. In addition, electrophoretic mobility shift assay (EMSA) was used to confirm whether this polymorphism has an effect on binding ability of the transcription factor. We found that the G variant significantly increased the transcription activity of the XRCC4 gene and the binding ability of transcriptional factor GATA-1 to the XRCC4 promoter. Furthermore, the results suggested that the XRCC4 protein and mRNA were overexpressed in individuals who carried the −652G allele compared to carriers of the −652T allele. In addition, the expression of XRCC4 in PCa tissues was lower than in adjacent normal tissues. Our data suggest that the XRCC4 promoter −652G>T polymorphism is functional and may influence genetic susceptibility to prostate cancer. Case–control studies are required to validate our findings in the future.

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Acknowledgments

This study was supported by National Natural Science Foundation of China (Grant No. 81272831, 81202034), Jiangsu Province’s Outstanding Medical Academic Leader program (RC201178), Six-Kinds-of-Top-Talent Program of Jiangsu Province (2011) and Science Foundation of Benq Medical Center (SRD20100004).

Conflict of interest

The authors declare no conflict of interest.

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Affiliations

  1. Department of Urology, Second People’s Hospital of Wuxi Affiliated to Nanjing Medical University, 68 Zhongshan Road, Wuxi, 214002, China

    Ning Shao, Yang Wang & NingHan Feng

  2. Department of Urology, BenQ Medical Center Affiliated to Nanjing Medical University, Nanjing, 210029, China

    JiuMing Li

  3. Department of Urology, Nanjing Zhongda Hospital Affiliated to Southeast University, Nanjing, China

    Bin Xu

  4. Translational Medicine Center, Second People’s Hospital of Wuxi Affiliated to Nanjing Medical University, 68 Zhongshan Road, Wuxi, 214002, China

    Ning Shao, Yang Wang, XiaoJie Lu & NingHan Feng

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  1. Ning Shao
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  2. JiuMing Li
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  4. Yang Wang
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Correspondence to XiaoJie Lu or NingHan Feng.

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Ning Shao and JiuMing Li authors have contributed equally to the present work and each is considered first author.

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Shao, N., Li, J., Xu, B. et al. Role of the functional variant (−652T>G) in the XRCC4 promoter in prostate cancer. Mol Biol Rep 41, 7463–7470 (2014). https://doi.org/10.1007/s11033-014-3636-1

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  • DOI: https://doi.org/10.1007/s11033-014-3636-1

Keywords

  • XRCC4
  • EMSA
  • Prostate cancer