Clinical Oral Investigations

, Volume 23, Issue 2, pp 829–838 | Cite as

Overexpression of nicotinamide N-methyltransferase in HSC-2 OSCC cell line: effect on apoptosis and cell proliferation

  • Riccardo Seta
  • Marco Mascitti
  • Roberto Campagna
  • Davide Sartini
  • Stefania Fumarola
  • Andrea Santarelli
  • Michele Giuliani
  • Monia Cecati
  • Lorenzo Lo Muzio
  • Monica EmanuelliEmail author
Original Article



Oral squamous cell carcinoma (OSCC) is the most common malignancy of oral cavity. Despite advances in therapeutic approaches, the 5-year survival rate for oral cancer has not improved in the last three decades. Therefore, new molecular targets for early diagnosis and treatment of OSCC are needed. In the present study, we focused on the enzyme nicotinamide N-methyltransferase (NNMT). We have previously shown that enzyme expression is upregulated in OSCC and NNMT knockdown in PE/CA PJ-15 cells significantly decreased cell growth in vitro and tumorigenicity in vivo.

Material and methods

To further explore the role of the enzyme in oral cancer cell metabolism, HSC-2 cells were transfected with the NNMT expression vector (pcDNA3-NNMT) and the effect of enzyme upregulation on cell proliferation was evaluated by MTT assay. Subsequently, we investigated at molecular level the role of NNMT on apoptosis and cell proliferation, by exploring the expression of β-catenin, survivin, and Ki-67 by real-time PCR. Moreover, we performed immunohistochemistry on 20 OSCC tissue samples to explore the expression level of NNMT and survivin ΔEx3 isoform.


Enzyme upregulation significantly increased cell growth in vitro. Moreover, a positive correlation between NNMT and survivin ΔEx3 isoform expression levels was found both in HSC-2 cells and in OSCC tissue samples.


Taken together, our results indicate a possible involvement of NNMT in the proliferation and tumorigenic capacity of OSCC cells and seem to suggest that the enzyme could represent a potential target for the treatment of oral cancer.

Clinical relevance

The involvement of NNMT in cell growth and anti-apoptotic mechanisms seems to suggest that this enzyme could be a new therapeutic target to improve the survival of OSCC patients.


NNMT Survivin Cell growth Tumorigenicity Oral cancer 



This study was supported by grants from Marche Polytechnic University.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Informed consent

For this type of study, formal consent is not required.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Riccardo Seta
    • 1
  • Marco Mascitti
    • 1
  • Roberto Campagna
    • 1
  • Davide Sartini
    • 1
  • Stefania Fumarola
    • 1
  • Andrea Santarelli
    • 1
  • Michele Giuliani
    • 2
  • Monia Cecati
    • 1
  • Lorenzo Lo Muzio
    • 2
  • Monica Emanuelli
    • 1
    Email author
  1. 1.Department of Clinical SciencesPolytechnic University of MarcheAnconaItaly
  2. 2.Department of Clinical and Experimental MedicineUniversity of FoggiaFoggiaItaly

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