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Published on: September 20, 2019
Overexpression of nicotinamide N-methyltransferase in HSC-2 OSCC cell line: effect on apoptosis and cell
Riccardo Seta1, Marco Mascitti1, Roberto Campagna1
1Department of Clinical Sciences, Polytechnic University of Marche, Via Ranieri 65, 60131, Ancona, Italy.
Objectives:
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.
Results:
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.
Conclusion:
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.
Insights
Nicotinamide N-methyltransferase (NNMT) promotes oral squamous cell carcinoma (OSCC) growth and survival. Targeting NNMT may offer a new therapeutic strategy for oral cancer patients.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Oral squamous cell carcinoma (OSCC) remains a significant health challenge with stagnant survival rates.
- Novel molecular targets are crucial for improving early diagnosis and treatment efficacy.
- Nicotinamide N-methyltransferase (NNMT) has been identified as an enzyme upregulated in OSCC.
Purpose of the Study:
- To investigate the role of NNMT in oral cancer cell metabolism and proliferation.
- To explore the molecular mechanisms by which NNMT influences OSCC cell growth and apoptosis.
- To evaluate NNMT and survivin ΔEx3 isoform expression in OSCC tissues.
Main Methods:
- Transfection of HSC-2 cells with NNMT expression vector.
- Cell proliferation assessment using MTT assay.
- Real-time PCR to analyze gene expression (β-catenin, survivin, Ki-67).
- Immunohistochemistry on OSCC tissue samples.
Main Results:
- NNMT upregulation significantly enhanced in vitro cell growth.
- A positive correlation was observed between NNMT and survivin ΔEx3 isoform expression in both cell lines and patient tissues.
- NNMT appears to influence cell proliferation and anti-apoptotic pathways.
Conclusions:
- NNMT is implicated in the proliferation and tumorigenic potential of OSCC.
- The enzyme's involvement in cell growth and anti-apoptotic mechanisms suggests it as a potential therapeutic target.
- Targeting NNMT could represent a novel strategy to improve survival rates for OSCC patients.
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