Tumor Biology

, Volume 37, Issue 7, pp 8741–8752 | Cite as

Identification of novel NRAGE involved in the radioresistance of esophageal cancer cells

  • Huandi Zhou
  • Ge Zhang
  • Xiaoying Xue
  • Yanling Yang
  • Ye Yang
  • Xiaojing Chang
  • Xiaohui Ge
  • Zhiqing Xiao
  • Han Guo
  • Yanqiang Wang
Original Article


Radiotherapy (RT) is one main method for the treatment of esophageal squamous cell carcinoma (ESCC), and the radioresistance is the predominant cause of patients with local recurrence. The previous results of gene microarray and subsequent verification showed that NRAGE might be involved in radiation resistance of ESCC cells. In this study, we reestablished human esophageal carcinoma radioresistant cell lines TE13R120 and ECA109R60 with gradient dose irradiation as previously reported, respectively. NRAGE expression was high in TE13R120 and ECA109R60 cells and was correlative with ionizing radiation (IR) resistance in clinic. However, the radiosensitivity of TE13R120 cells had a remarkable increase detected by colony formation assays after siRNA against NRAGE (siNRG) transfection into TE13R120 cells. Compared with TE13 cells, an increasing number of TE13R120 cells with NRAGE overexpression in S phase and a lower ratio in G2/M were observed by flow cytometry method (FCM). Intriguingly, the above changes were partially reversed in TE13R120 cells treated with siNRG. More importantly, the ectopic subcellular localization of NRAGE mediated nuclear translocation of β-catenin which may be one reason of IR resistance of esophageal carcinoma cell. These data indicate that NRAGE extremely may be a pivotal factor involved in Wnt/β-catenin signal pathway, mediating nuclear translocation of β-catenin and then facilitating the formation of radioresistance of ESCC.


Esophageal squamous cell carcinoma Radioresistance NRAGE β-catenin Subcellular localization 



This work was supported by the Natural Science Foundation of Hebei Province (Grant No. C2009001151; recipient: Xiaoying Xue) and the Foundation of the Second Hospital of Hebei Medical University (Grant No. 2h2201505; recipient: Xiaoying Xue). We thank Professor Yonghong Shi at the Department of Pathology, Basic Medical Science of Hebei Medical University.

Compliance with ethical standards

Conflicts of interest


Ethical approval

All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. And the study was approved by the Ethics Committee of Second Hospital of Hebei Medical University.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

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Table S1

The specific primers of real-time PCR (GIF 54 kb)

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High resolution image (TIF 1079 kb)
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Table S2

The primers of siRNA (GIF 37 kb)

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High resolution image (TIF 805 kb)
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Fig. S1

Compared the characteristics between ECA109 and ECA109R60 (GIF 28 kb)

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High resolution image (TIF 1660 kb)
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Fig. S2

Tested the expression of NRAGE in ECA109 and ECA109R60 cells by Immunofluorescence (GIF 24 kb)

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High resolution image (TIF 1328 kb)
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Fig. S3

The difference of β-catenin expression in ECA109 and ECA109R60 cells (GIF 7 kb)

13277_2015_4747_MOESM5_ESM.tif (38 kb)
High resolution image (TIF 237 kb)


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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2016

Authors and Affiliations

  • Huandi Zhou
    • 1
  • Ge Zhang
    • 1
  • Xiaoying Xue
    • 1
  • Yanling Yang
    • 1
  • Ye Yang
    • 1
  • Xiaojing Chang
    • 1
  • Xiaohui Ge
    • 1
  • Zhiqing Xiao
    • 1
  • Han Guo
    • 1
  • Yanqiang Wang
    • 1
  1. 1.Department of RadiotherapyThe Second Hospital of Hebei Medical UniversityShijiazhuangChina

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