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Overexpression of MYCN promotes proliferation of non-small cell lung cancer

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Tumor Biology

Abstract

V-myc avian myelocytomatosis viral oncogene neuroblastoma derived homolog (MYCN) is an oncogene that is known amplified and overexpressed in different human malignancies including small cell lung cancer. However, the role of MYCN in non-small cell lung cancer (NSCLC) development remains elusive. In the present study, Western blot and immunohistochemistry assays demonstrated that MYCN was overexpressed in NSCLC tumor tissues and cell lines. In addition, immunohistochemistry analysis revealed that upregulation of MYCN expression was positively correlated with a more invasive tumor phenotype and poor prognosis. In vitro studies using serum starvation-refeeding experiment and MYCN-siRNA transfection assay demonstrated that MYCN expression promoted proliferation of NSCLC cells, while MYCN knockdown led to decreased cell growth resulted from growth arrest of cell cycle at G0/G1 phase. Furthermore, upregulation and knockdown of sex-determining region Y-box 2 (SRY) (SOX2), which was a well-known oncogene, confirmed that MYCN might be a downstream gene of the transcription factor SOX2. Collectively, our finding suggested that MYCN might contribute to the progression of NSCLC by enhancing cell proliferation, and that targeting MYCN might provide beneficial effects for the clinical therapy of NSCLC.

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (no. 81501975), University Science Research Project of Jiangsu Province (15KJB310013), Six Talent Peaks Project in Jiangsu Province (nos. 2014-YY-006 and WSN-059), Nantong Science and Technology Project (MS12015103 and HS2012025), and Nantong University Innovation Project (YKC15087).

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    Authors and Affiliations

    1. Department of Cardiothoracic Surgery, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, China

      Kun Liu & Shuo Wang

    2. Department of Pathology, Medical School of Nantong University, Nantong, 226001, Jiangsu, China

      Shuo Wang, Zhiwen Wang & Lili Ji

    3. Jiangsu Province Key Laboratory for Inflammation and Molecular Target, Medical School of Nantong University, Nantong, 226001, Jiangsu, China

      Shuo Wang, Yingying Chen & Lili Ji

    4. Department of Pathology, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, China

      Yifei Liu

    5. Department of Respiratory, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, China

      Jun Gu & Rui Zhang

    6. Department of Oncology, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, China

      Shudong Gu, Zhen Xu & Yingying Chen

    7. Department of Otorhinolaryngology, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, China

      Huaci Ma

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    1. Kun Liu
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    Correspondence to Lili Ji.

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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.

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    Kun Liu and Shuo Wang contributed equally to this work.

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    Liu, K., Wang, S., Liu, Y. et al. Overexpression of MYCN promotes proliferation of non-small cell lung cancer. Tumor Biol. 37, 12855–12866 (2016). https://doi.org/10.1007/s13277-016-5236-2

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    • DOI: https://doi.org/10.1007/s13277-016-5236-2

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