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

Tumour Biol. 2016 Sep;37(9):12855-12866. doi: 10.1007/s13277-016-5236-2. Epub 2016 Jul 23.

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.

Keywords: Cell cycle; MYCN; NSCLC; Proliferation; SOX2.

MeSH terms

  • A549 Cells
  • Blotting, Western
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Line, Tumor
  • Cell Proliferation*
  • Female
  • G1 Phase Cell Cycle Checkpoints
  • Humans
  • Immunohistochemistry
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • N-Myc Proto-Oncogene Protein / genetics
  • N-Myc Proto-Oncogene Protein / metabolism*
  • Prognosis
  • RNA Interference
  • Resting Phase, Cell Cycle
  • SOXB1 Transcription Factors / genetics
  • SOXB1 Transcription Factors / metabolism
  • Up-Regulation

Substances

  • MYCN protein, human
  • N-Myc Proto-Oncogene Protein
  • SOX2 protein, human
  • SOXB1 Transcription Factors