Abstract
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.
Highlights
Introduction published maps and institutional affilThe head and neck tumors (HNT) are a heterogeneous group of lesions with different embryological and histological origins that range from benign to malignant entities, arising from tissues of the head and neck region [1]
Given the evidence that nicotinamide N-methyltransferase (NNMT) contributes to carcinogenesis, this report aims to conduct a comprehensive narrative review of all of the available literature regarding the biological, diagnostic, and prognostic role of NNMT in HNT
In TE1-negative control (NC) tumor, the knockdown of NNMT, and even more with the 5-FU treatment, significantly decreased the expression of glycolysis-related enzymes. These results suggested that NNMT may decrease the 5-FU sensitivity of the Esophageal squamous cell carcinoma (ESCC) cells by promoting glucose metabolism which is closely correlated with cancer cell drug resistance
Summary
The head and neck tumors (HNT) are a heterogeneous group of lesions with different embryological and histological origins that range from benign to malignant entities, arising from tissues of the head and neck region [1]. Within the HNT group, the salivary gland tumors, a group of lesions that are characterized by heterogeneous histopathological and clinical presentations, and odontogenic tumors, a group of hard tissue neoplasms derived from the tooth-forming apparatus are included [3]. Other tumor types, such as mucosal melanomas, esophageal, and thyroid cancers are not universally accepted as part of HNT. HNT are highly heterogeneous in terms of epidemiology, risk factors, clinical manifestations, and prognosis
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