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Virchows Archiv

, Volume 471, Issue 6, pp 743–751 | Cite as

HCRP1 downregulation confers poor prognosis and induces chemoresistance through regulation of EGFR-AKT pathway in human gastric cancer

  • Hao Xu
  • Zhi-Feng Miao
  • Zhen-Ning Wang
  • Ting-Ting Zhao
  • Ying-Ying Xu
  • Yong-Xi Song
  • Jin-Yu Huang
  • Jun-Yan Zhang
  • Xing-Yu Liu
  • Jian-Hua Wu
  • Hui-Mian XuEmail author
Original Article

Abstract

The current study aims to investigate the biological roles and clinical significance of HCRP1 in human gastric cancer. The expression pattern of HCRP1 in gastric cancer tissue and adjacent non-cancerous tissue was detected by immunohistochemistry. HCRP1 downregulation was found in 57 of 137 human gastric cancer samples and correlated with advanced TNM stage, positive nodal status, and relapse. Log-rank test showed that HCRP1 downregulation also correlated with poor overall survival and reduced relapse-free survival. In addition, we found that HCRP1 overexpression inhibited proliferation, colony formation, and invasion in HGC-27 cells. On the other hand, HCRP1 depletion by small interfering RNA promoted proliferation, colony formation, and invasion in SGC-7901 cells. We also treated gastric cancer cells with cisplatin. MTT and Annexin V/PI analysis were carried out to examine change of chemoresistance. We found that HCRP1 overexpression sensitized HGC-27 cells to cisplatin while its depletion reduced sensitivity in SGC-7901 cells. Moreover, we found that HCRP1 overexpression negatively regulated cyclin D1, MMP-2, p-EGFR, p-ERK, and p-AKT. HCRP1 depletion showed the opposite effects. In conclusion, our results suggest that HCRP1 downregulation might serve as an indicator for poor prognosis in gastric cancer patients. HCRP1 reduces drug resistance through regulation of EGFR-AKT signaling.

Keywords

HCRP1 Gastric cancer Cell cycle Resistance 

Notes

Acknowledgements

We thank Prof. Feng Li for technical guidance and assistance.

Author contribution

Hao Xu and Zhi-Feng Miao designed the study and wrote the manuscript; Hao Xu and Zhen-Ning Wang collected the tissue sections; Hui-Mian Xu contributed to the study design and paper accomplishment; Ting-Ting Zhao and Ying-Ying Xu performed the MTT and flow cytometry assays; Hao Xu and Yong-Xi Song performed the cell culture, transfection, and western blot assays; Zhi-Feng Miao, Jin-Yu Huang, and Jun-Yan Zhang performed the immunohistochemistry, colony formation, and matrigel invasion assay; Xing-Yu Liu and Jian-Hua Wu analyzed the data. All authors participated in discussing the content of the paper and read and approved the final manuscript.

Funding

This work was supported by the National Science Foundation of China (grant numbers: 81272718 and 81302125).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.

Ethical approval

The protocols of this study have been approved by the Ethics committee of China Medical University (reference number 2016-AF-03).

Supplementary material

428_2017_2237_Fig6_ESM.gif (24 kb)
Supplementary Figure 1

Validation of antibody. HCRP1 antibody showed positive cytoplasmic staining in a case of normal gastric tissue. Using western blot, HCRP1 antibody detect a single band in this normal tissues and cells. The intensity decreased significantly in cells with HCRP1 depletion. (GIF 23 kb)

428_2017_2237_MOESM1_ESM.tif (303 kb)
High resolution image (TIFF 302 kb)

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Copyright information

© Springer-Verlag GmbH Deutschland 2017

Authors and Affiliations

  • Hao Xu
    • 1
  • Zhi-Feng Miao
    • 1
  • Zhen-Ning Wang
    • 1
  • Ting-Ting Zhao
    • 2
  • Ying-Ying Xu
    • 2
  • Yong-Xi Song
    • 1
  • Jin-Yu Huang
    • 1
  • Jun-Yan Zhang
    • 1
  • Xing-Yu Liu
    • 1
  • Jian-Hua Wu
    • 1
  • Hui-Mian Xu
    • 1
    Email author
  1. 1.Department of Surgical OncologyFirst Hospital of China Medical UniversityShenyangChina
  2. 2.Department of Breast SurgeryFirst Hospital of China Medical UniversityShenyangChina

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