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The tumor promoting roles of erythropoietin/erythropoietin receptor signaling pathway in gastric cancer

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Tumor Biology

Abstract

Erythropoietin (EPO), binding with its receptor (EPOR), plays an important role in erythropoiesis. EPOR is reported to be expressed in various non-hematopoietic cancers, including gastric cancer. Although recombinant human EPO (rhEPO) has been widely used clinically in anemia patients, it remains controversial whether it would promote tumor progression. In this study, we used siRNA interference method to downregulate EPOR expression to investigate the function of EPO/EPOR pathway in human gastric cancer cells. We found EPOR expressed significantly higher in gastric cancer tissues, and also in most gastric cancer cell lines. RhEPO promoted gastric cancer cell proliferation, migration in AGS cells, and promoted cells from G0/G1 stage to G2/M stage, but had no regulation on AGS cell apoptosis. Downregulation of EPOR expression by siRNA interference in AGS cells resulted in no significant effects on proliferation and invasiveness of the cells, but induced apoptosis (p < 0.05). Xenografted gastric tumor model was used to explore the effect of EPOR-overexpression on gastric cancer cells in vivo. Our result showed that overexpression of EPOR enhanced tumor formation in nude mice (p < 0.01). Our results suggest that EPO/EPOR pathway promotes gastric cancer formation, proliferation, migration, and decreases apoptosis.

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Acknowledgments

This work was funded by National Natural Science Foundation of China (81401733), Natural Science Foundation of Zhejiang Province (LY14H160029), Healthy and Family Planning Commission of Zhejiang Province (201231956), and Zhejiang province key science and technology innovation team (2013TD13).

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    Authors and Affiliations

    1. Department of Gastroenterology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, Zhejiang, 310016, China

      Weiling Hu, Yu Zhang, Lan Wang, Jun Li, Shujie Chen, Ning Dai & Jianmin Si

    2. Institute of Gastroenterology, Zhejiang University, Hangzhou, Zhejiang, 310016, China

      Weiling Hu, Yu Zhang, Lan Wang, Jun Li, Shujie Chen, Ning Dai & Jianmin Si

    3. Department of Pathology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, Zhejiang, China

      Zhinong Jiang

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    1. Weiling Hu
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    Correspondence to Weiling Hu or Jianmin Si.

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    Weiling Hu and Yu Zhang contributed equally to this work.

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    Hu, W., Zhang, Y., Jiang, Z. et al. The tumor promoting roles of erythropoietin/erythropoietin receptor signaling pathway in gastric cancer. Tumor Biol. 37, 11523–11533 (2016). https://doi.org/10.1007/s13277-016-5053-7

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