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Cyclophilin A Enhances Cell Proliferation and Xenografted Tumor Growth of Early Gastric Cancer

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Abstract

Background

Recently Cyclophilin A (CypA) was identified as a candidate target protein in gastric carcinoma. However, the role of CypA in gastric cancer (GC) has not been investigated extensively so far.

Aim

The purpose of this study was to determine the expression pattern of CypA in human GC, and to explore the effects of suppressed CypA expression on cell proliferation and xenografted tumor growth of gastric cancer.

Methods

In the present study, we detected the expression pattern of CypA in human GC by immunohistochemistry analysis. Further, the RNAi method was used to silence CypA, and colony formation assay, growth curves, cell cycle and mouse xenograft were analysed.

Results

An elevated expression of CypA in GC tissues compared with normal gastric mucosa was observed, especially in TNM stage-I and intestinal type of tumor. CypA was overexpressed in most GC cell lines and endogenous expression of CypA correlated with cell growth phenotypes. Transient suppression of CypA reduced the proliferation of BGC-823 and SGC-7901 GC cell lines. Exogenous CypA promoted the proliferation of NCI-N87 GC cells in a concentration dependent manner. Further study revealed that stable CypA silencing inhibited the proliferation, prevented cell cycle and reduced autophagy of BGC-823 GC cells in vitro through suppressing the ERK1/2 signal pathway. Stable CypA silencing also inhibited the growth of xenografted tumor of BGC-823 GC cell in nude mice.

Conclusions

These results indicate a special function mode for CypA of playing more important roles in the early stage of gastric tumorigenesis and suggest CypA as a new molecular target of diagnosis and treatment for GC patients.

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (Nos. 81071650; 30973503; 81050007); Special foundation for Science and Technology Program in Liaoning Province, China (2013225303-103; 2011404013-3); the Supporting Project for Climbing Scholars in Liaoning Provincial Universities, China (2009–2012).

Conflict of interest

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Authors and Affiliations

  1. Department of Gastrointestinal Tumor Pathology of Cancer Institute and General Surgery Institute, The First Hospital of China Medical University, 155 Nanjing North Street, Heping District, Shenyang, 110001, China

    Wenhua Feng, Yan Xin, Yuping Xiao, Wenhui Li & Dan Sun

  2. Key Laboratory of Reproductive Health and Medical Genetics, National Health and Family Planning Commission, Shenyang, China

    Wenhua Feng

  3. Key Laboratory of Reproductive Health of Liaoning, Shenyang, China

    Wenhua Feng

Authors
  1. Wenhua Feng
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  2. Yan Xin
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  3. Yuping Xiao
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  4. Wenhui Li
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  5. Dan Sun
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Corresponding author

Correspondence to Yan Xin.

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Feng, W., Xin, Y., Xiao, Y. et al. Cyclophilin A Enhances Cell Proliferation and Xenografted Tumor Growth of Early Gastric Cancer. Dig Dis Sci 60, 2700–2711 (2015). https://doi.org/10.1007/s10620-015-3694-9

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  • DOI: https://doi.org/10.1007/s10620-015-3694-9

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