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

Seta, Riccardo; Mascitti, Marco; Campagna, Roberto; Fumarola, Stefania; Santarelli, Andrea; Giuliani, Michele; Cecati, Monia; Muzio, Lorenzo Lo; Emanuelli, Monica

doi:10.1007/s00784-018-2497-8

Cited by 32 publications

(37 citation statements)

References 31 publications

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“…Results obtained showed that Ki-67 levels did not undergo dysregulation upon induction of NNMT upregulation, thus suggesting that proliferative capacity of cancer cell is a complex phenotypical aspect regulated by the combined effects of different molecular determinants. 35 In conclusion, this report is the first to evaluate NNMT expression in odontogenic lesions and to demonstrate a differential expression between recurrent AMs and OKCs.…”

mentioning

confidence: 65%

“…Concerning cell proliferation, Ki‐67 expression was therefore investigated. Results obtained showed that Ki‐67 levels did not undergo dysregulation upon induction of NNMT upregulation, thus suggesting that proliferative capacity of cancer cell is a complex phenotypical aspect regulated by the combined effects of different molecular determinants …”

Section: Discussionmentioning

confidence: 96%

“…Although NNMT is mainly expressed in the liver, a low expression has been also detected in the kidney, lung, skeletal muscle, placenta, heart and brain . Overexpression of NNMT has been reported in many cancers, such as glioblastoma, renal, lung and oral malignancies, suggesting that the enzyme may play an important role in malignant transformation . NNMT overexpression affects cell resistance to radiation‐induced damage and is positively correlated with enhanced cancer cell migration and poor prognosis .…”

Section: Introductionmentioning

confidence: 99%

“…9 Overexpression of NNMT has been reported in many cancers, such as glioblastoma, renal, lung and oral malignancies, suggesting that the enzyme may play an important role in malignant transformation. [12][13][14][15] NNMT overexpression affects cell resistance to radiation-induced damage 16 and is positively correlated with enhanced cancer cell migration and poor prognosis. 17,18 These data seem to suggest the potential prognostic role of NNMT in several neoplasms.…”

Section: Introductionmentioning

confidence: 99%

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Differential expression of nicotinamide N‐methyltransferase in primary and recurrent ameloblastomas and odontogenic keratocysts

Mascitti

Togni

Pozzi

et al. 2020

Eur J Clin Investigation

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Background Odontogenic tumours are a group of rare heterogeneous diseases that range from hamartomatous tissue proliferations to benign and malignant neoplasms. Recurrences can occur after 10 years, so long‐term clinical and radiological follow‐up is required. The study of the molecular mechanisms involved in the development of these lesions is necessary to identify new prognostic markers. In this study, we evaluate the possible role of nicotinamide N‐methyltransferase (NNMT) in ameloblastomas (AM) and odontogenic keratocysts (OKC). Materials and methods A total of 105 surgical specimens of primary and recurrent lesions were obtained from 55 patients (25 AM, 30 OKC). In particular, 50 AMs (25 primary, 25 recurrences) and 55 OKCs (30 primary, 25 recurrences) were retrieved. We carried out immunohistochemical analyses to evaluate the cytoplasmic expression of NNMT, measuring the percentage of positive cells and the value of NNMT expression intensity. Results NNMT expression was significantly higher in recurrent than primary AMs (P = .0430). This result was confirmed by staining intensity, showing more cases with moderate/intense staining in recurrent AMs (P = .0470). NNMT expression was significantly lower in recurrent than primary OKC (P = .0014). Staining intensity showed more cases with moderate/intense staining in primary OKCs (P = .0276). Conclusions This report is the first to evaluate NNMT expression in odontogenic lesions and to demonstrate a differential expression in recurrent AMs and OKCs, suggesting that there is potential for use of NNMT as prognostic marker.

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confidence: 65%

Section: Discussionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Differential expression of nicotinamide N‐methyltransferase in primary and recurrent ameloblastomas and odontogenic keratocysts

Mascitti

Togni

Pozzi

et al. 2020

Eur J Clin Investigation

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“…24 On the contrary, the induction of enzyme overexpression in HSC-2 oral cancer cells significantly enhanced in vitro cell proliferation. 25 These data demonstrated a pivotal role played by the enzyme in cancer cell metabolism and suggests that NNMT could represent an important molecular target for anticancer therapy.…”

Section: Introductionmentioning

confidence: 88%

Nicotinamide N‐methyltransferase in nonmelanoma skin cancers

Pompei

Salvolini

Rubini

et al. 2019

Eur J Clin Investigation

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Background Squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) represent the most common forms of nonmelanoma skin cancers (NMSCs). Although successful treatment of these neoplasms is based on surgical excision, an increasing number of BCCs relapses and many SCCs display high rates of recurrence and metastasis. Nicotinamide N‐methyltransferase (NNMT) is a cytosolic enzyme, which was found to be upregulated in different solid tumours. However, there are no data regarding enzyme expression in NMSCs. The aim of this study was therefore to evaluate the potential involvement of NNMT in BCCs and SCCs. Materials and methods Immunohistochemical analyses were carried out on 40 BCC cases and 39 SCC cases, to evaluate enzyme expression in tumour and surrounding healthy margins. Moreover, the relationship between NNMT intratumour levels and clinico‐pathological parameters were explored. Results Nicotinamide N‐methyltransferase was found to be overexpressed in BCCs compared with control tissues, while a significant enzyme downregulation was detected in SCCs with respect to corresponding healthy margins. In addition, NNMT levels were negatively related to aggressiveness of both BCCs (distinguishing between infiltrative and nodular tumours) and SCCs (considering head and neck forms and tumours of the extremities and trunk). Conclusions These evidences seem to demonstrate that the different NNMT dysregulation detected in BCC and SCC may be the result of important biological traits distinctively characterizing these two forms within NMSCs. In addition, enzyme levels seem to be inversely correlated with tumour aggressiveness, thus suggesting the potential suitability of the enzyme as a prognostic biomarker for both neoplasms.

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Nicotinamide N‐methyltransferase is related to MELF pattern invasion in endometrioid carcinoma

et al. 2021

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Grade 1 (G1) endometrioid carcinoma (EC) is relatively a good prognosis. However, in a minority of cases, G1 shows an aggressive histological pattern known as the microcystic, elongated, and fragmented (MELF) pattern. We previously reported that EC with high expression levels of S100A4 and serum deprivation‐response protein (SDPR) was related to MELF pattern invasion. However, the molecular features of the invasive front area of the MELF pattern have not been investigated. In this study, we searched for genes preferentially expressed in the invasive front area of EC with the MELF pattern using laser microdissection and RNA sequencing, and showed that nicotinamide N‐methyltransferase (NNMT) is related to MELF pattern invasiveness. Immunohistochemical analyses confirmed high NNMT expression in the invasive front area of the MELF pattern. Moreover, NNMT promoted migration, invasion, colony formation, epithelial–mesenchymal transition (EMT), and chemoresistance using EC cell lines. We speculate that depletion of NNMT promotes histone methylation and leads to tumor suppression because NNMT consumes S‐adenosyl methionine (SAM), which is an essential methylation cofactor. NNMT knockout cells showed enhanced expression of H3K9me2. RNA sequencing using NNMT knockout cell lines suggested that methylation of H3K9 leads to repression of the transcription of various oncogenic genes. Our findings demonstrate the possibility that NNMT inhibitors, which are expected to be used for the treatment of metabolic disorders, would be effective for the treatment of aggressive EC. This is the first report of gene analyses focusing on the morphological changes associated with MELF pattern invasion of EC.

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

Abstract: 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.

Cited by 32 publications

References 31 publications

Differential expression of nicotinamide N‐methyltransferase in primary and recurrent ameloblastomas and odontogenic keratocysts

Differential expression of nicotinamide N‐methyltransferase in primary and recurrent ameloblastomas and odontogenic keratocysts

Nicotinamide N‐methyltransferase in nonmelanoma skin cancers

Nicotinamide N‐methyltransferase is related to MELF pattern invasion in endometrioid carcinoma

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