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Role of nicotinamide N-methyltransferase in non-small cell lung cancer: in vitro effect of shRNA-mediated gene silencing on tumourigenicity

  • Davide Sartini EMAIL logo , Riccardo Seta , Valentina Pozzi , Stefano Morganti , Corrado Rubini , Antonio Zizzi , Marco Tomasetti , Lory Santarelli and Monica Emanuelli
Published/Copyright: September 8, 2014
Biological Chemistry
From the journal Biological Chemistry Volume 396 Issue 3

Abstract

Lung cancer is the second most commonly diagnosed neoplasm, and represents the leading cause of tumour death worldwide. As patients are often diagnosed at a late stage, current therapeutic strategies have limited effectiveness and the prognosis remains poor. Successful treatment depends on early diagnosis and knowledge concerning molecular mechanisms underlying lung carcinogenesis. In the present study, we focused on nicotinamide N-methyltransferase (NNMT), which is overexpressed in several malignancies. First, we analysed NNMT expression in a cohort of 36 patients with non-small cell lung cancer (NSCLC) by immunohistochemistry. Subsequently, we examined NNMT expression levels in the human lung cancer cell line A549 by Real-Time PCR, Western blot and catalytic activity assay, and evaluated the effect of NNMT knockdown on cell proliferation and anchorage-independent cell growth by MTT and soft agar colony formation assays, respectively. NSCLC displayed higher NNMT expression levels compared to both tumour-adjacent and surrounding tissue. Moreover, shRNA-mediated gene silencing of NNMT led to a significant inhibition of cell proliferation and colony formation ability on soft agar. Our results show that the downregulation of NNMT significantly reduced in vitro tumorigenicity of A549 cells and suggest that NNMT could represent an interesting molecular target for lung cancer therapy.

Keywords: anchorage-independent cell growth; cancer cell line; cell proliferation; knockdown; nicotinamide N-methyltransferase (NNMT); non-small cell lung cancer (NSCLC)
Corresponding author: Davide Sartini, Department of Clinical Sciences, Polytechnic University of Marche, Via Ranieri 65, I-60131 Ancona, Italy, e-mail:

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Received: 2014-7-24
Accepted: 2014-9-3
Published Online: 2014-9-8
Published in Print: 2015-3-1

©2015 by De Gruyter

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https://doi.org/10.1515/hsz-2014-0231
Keywords for this article
anchorage-independent cell growth; cancer cell line; cell proliferation; knockdown; nicotinamide N-methyltransferase (NNMT); non-small cell lung cancer (NSCLC)

Articles in the same Issue

  1. Frontmatter
  2. Reviews
  3. The emerging role of the peptidome in biomarker discovery and degradome profiling
  4. Inflammatory caspases: key regulators of inflammation and cell death
  5. Minireview
  6. The role of serpins in tumor cell migration
  7. Research Articles/Short Communications
  8. Protein Structure and Function
  9. A core domain of the BMP2 proregion is sufficient for the biogenesis of mature homodimeric growth factor
  10. Molecular Medicine
  11. Role of nicotinamide N-methyltransferase in non-small cell lung cancer: in vitro effect of shRNA-mediated gene silencing on tumourigenicity
  12. Cell Biology and Signaling
  13. miR-103 promotes 3T3-L1 cell adipogenesis through AKT/mTOR signal pathway with its target being MEF2D
  14. miR-126 modulates angiogenic growth parameters of peripheral blood endothelial progenitor cells
  15. Osteoblastic alkaline phosphatase mRNA is stabilized by binding to vimentin intermediary filaments
  16. Proteolysis
  17. Mirolase, a novel subtilisin-like serine protease from the periodontopathogen Tannerella forsythia
  18. Cathepsin B-deficient mice as source of monoclonal anti-cathepsin B antibodies
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