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ECRG4 as a novel tumor suppressor gene inhibits colorectal cancer cell growth in vitro and in vivo

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Tumor Biology

Abstract

Esophageal cancer related gene 4 (ECRG4) as a tumor suppressor gene inhibits the growth and development of various tumors. Colorectal cancer (CRC), a common malignant tumor in the digestive tract worldwide, is a leading cause of death. The aim of our study was to assess the tumor-suppressing effect of ECRG4 on CRC and explore its related mechanisms in vitro and in vivo. The expression levels of ECRG4 were measured in colorectal cancer tissues and para-carcinoma tissues. ECRG4 gene was transfected into CRC cells to investigate its effect on cell proliferation by MTT, colony formation assay, and cell cycle analysis. Cell apoptosis was assessed by annexin-V/PI, Hoechst 33342 staining, and analysis of apoptosis-related protein expressions in vitro. The in vivo tumorigenesis assays were performed in nude mice. According to the results, there was a lower expression of ECRG4 in CRC tissues compared with normal tissues, which was strongly associated with histology differentiation and lymph node metastasis. Additionally, overexpression of ECRG4 had a significant inhibitory effect on proliferation and promoted apoptosis in Caco-2 and SW480 cells. Moreover, we found that the overexpression of ECRG4 inhibited tumorigenesis in vivo by diminishing the volume and weight of the tumors and inducing apoptosis of tumor cells. Our study indicates that ECRG4 may be a new potential target and prognostic factor for patients with CRC.

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Acknowledgments

This study was supported by grants from the National Natural Science Foundation of China (No. 81273919), the University Talent Support Program of Liaoning Province (No. LJQ2013094), the Natural Science Foundation of Liaoning Province (No. 2013023002), the Science and Technology Project of Liaoning Province (2012225020), and the National Basic Research Program of China (973 Program, No. 2013CB531703).

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    Authors and Affiliations

    1. Department of Internal Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, 116011, People’s Republic of China

      Zhengxu Cai

    2. Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, 116011, People’s Republic of China

      Pin Liang

    3. Department of Pathology, The First Affiliated Hospital of Dalian Medical University, Dalian, 116011, People’s Republic of China

      Jize Xuan

    4. Central Laboratory, The First Affiliated Hospital of Dalian Medical University, 222 Zhongshan Road, Dalian, 116011, People’s Republic of China

      Jiajia Wan & Huishu Guo

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    1. Zhengxu Cai
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    Correspondence to Huishu Guo.

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    All procedures performed in studies 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.

    All animal experiments were carried out strictly in accordance with international ethical guidelines and the National Institutes of Health Guide concerning the Care and Use of Laboratory Animals. The experiments were approved by the Institutional Animal Care and Use Committee of Dalian Medical University.

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    Zhengxu Cai and Pin Liang contributed equally to this work.

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    Cai, Z., Liang, P., Xuan, J. et al. ECRG4 as a novel tumor suppressor gene inhibits colorectal cancer cell growth in vitro and in vivo. Tumor Biol. 37, 9111–9120 (2016). https://doi.org/10.1007/s13277-015-4775-2

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    • DOI: https://doi.org/10.1007/s13277-015-4775-2

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