The head and neck
tumors (HNT) are a heterogeneous group of diseases ranging from benign to malignant lesions, with distinctive molecular and clinical behaviors. Several studies have highlighted the presence of an altered metabolic phenotype in HNT, such as the upregulation of
nicotinamide N-methyltransferase (
NNMT). However, its biological effects have not been completely disclosed and the role of
NNMT in
cancer cell metabolism remains unclear. Therefore, this comprehensive review aims to evaluate the available literature regarding the biological, diagnostic, and prognostic role of
NNMT in HNT.
NNMT was shown to be significantly overexpressed in all of the evaluated HNT types. Moreover, its upregulation has been correlated with
cancer cell migration and adverse clinical outcomes, such as high-pathological stage,
lymph node metastasis, and locoregional recurrences. However, in
oral squamous cell carcinoma (OSCC) these associations are still debated, and several studies have failed to demonstrate the prognostic significance of
NNMT. The
shRNA-mediated gene silencing efficiently suppressed the
NNMT gene expression and exhibited a clear inhibitory effect on cell proliferation, promoting the expression of apoptosis-related
proteins and modulating the cell cycle.
NNMT could represent a new molecular
biomarker and a new target of molecular-based
therapy, although further studies on larger patient cohorts are needed to explore its biological role in HNT.