Table 1.
Summary of the literature data on the role of NNMT in HNT.
| Author, Year [ref] | Tumor Type | Methods | Materials | Main Results |
|---|---|---|---|---|
| Sartini D et al., 2007 [25] | OSCC | IHC | Rabbit polyclonal anti-human NNMT Ab, 1:500 | NNMT expression in N0 OSCC is higher than N+ OSCC and normal tissues. Inverse association between NNMT expression and tumor size and pathological staging. |
| Roberg K et al., 2008 [26] | OSCC | Genomic study | Genomic microarray [Affymetrix HG-Focus chip] (LK0412 cell line) | NNMT expression is 74-fold change higher in OSCC than in normal oral keratinocytes. |
| Emanuelli M et al., 2010 [29] | OSCC | IHC | Rabbit polyclonal anti-human NNMT Ab, 1:500 | NNMT immunostaining is higher in tumor tissue compared to normal mucosa. Moreover, there is an inverse relationship between NNMT expression and histological grading. |
| Liao KA et al., 2011 [32] | OSCC | Proteomic study | Liquid chromatography-mass spectrometry [LTQ-Orbitrap hybrid tandem mass spectrometer and Agilent 1200 nanoflow HPLC] (OSCC and adjacent non tumor tissue) | A total of 17 proteins were differentially expressed in OSCC compared to non-tumor tissue, including NNMT. |
| IHC | Rabbit polyclonal anti-human NNMT Ab, 1:50 | The expression of three proteins, including NNMT, confirmed the proteomic data. | ||
| Sartini D et al., 2012 [19] | OSCC | In vitro study | Frozen OSCC tissue samples | Increase of NNMT enzyme activity from non-tumor tissue to OSCC and from N0 to N+ OSCC. |
| Clinical study | Saliva from OSCC patients and healthy subjects | Salivary NNMT levels higher in OSCC patients than in healthy subjects. | ||
| Pozzi V et al., 2013 [27] | OSCC | In vitro study | PE/CA PJ-15 cell line | NNMT gene silencing reduce cell proliferation and colony formation ability. |
| In vivo study | BALB/c nude mice | NNMT silencing reduce tumor volume. | ||
| Jiang Q et al., 2014 [31] | OSCC | Bioinformatic study | Bioinformatic analysis based on genomic microarray [Affymetrix Human Genome U133A Array] | NNMT found to be overexpressed (>1-fold change) compared to normal oral mucosa. |
| Chakrabarti S et al., 2015 [30] | OSCC | Genomic study | Genomic microarray [IlluminaSentrix Human Ref-8 v2 Expression BeadChip arrays] (OSCC patients and healthy subjects) | NNMT expression in OSCC is higher (2.39-fold change) than in normal mucosa. |
| Seta R et al., 2019 [28] | OSCC | In vitro study | HSC-2 cell line | NNMT overexpression increase cell growth in vitro. Moreover, NNMT is associated to survivin-ΔEx3 isoform expression. |
| Ishibashi K et al., 2018 [35] | AdCC | In vitro study | ACCS-GFP, ACCS-M-GFP, ACCS-LN-GFP cell lines | NNMT mRNA and protein levels increase from ACCS-GFP line to ACCS-M-GFP and to ACCS-LN-GFP cell line. |
| Genomic study | Genomic microarray [60K Agilent 60-mer oligomicroarray] (ACCS-M-GFP, ACCS-LN-GFP cell lines) | NNMT expression is higher (2.0-fold change) in ACCS-LN-GFP than in ACCS-M-GFP. | ||
| Mascitti M et al., 2019 [37] | OMM | IHC | Rabbit polyclonal anti-human NNMT Ab, 1:1500 | NNMT intensity is higher in ulcerated OMM compared to no-ulcerated OMM. NNMT overexpression negatively affects the DFS. |
| Mascitti M et al., 2020 [36] | OT | IHC | Rabbit polyclonal anti-human NNMT Ab, 1:1500 | NNMT expression is higher in recurrent than primary lesions. |
| Xu J et al., 2003 [39] | thyroid cancer | In vitro study | BHP2-7, BHP5-16, BHP 7-13, BHP 10-3, BHP 14-9, BHP 15-3, BHP 17-10, BHP 18-21, ARO 81-1, DRO 90-1, HRO 85-1, DRO 81-1, WRO 82-1, TC1 cell lines | NNMT mRNA and catalytic activity are higher in BHP 2-7, BHP 7-13, BHP 10-3, BHP 18-21 and TPC1, compared to other cancer cell types and thyroid primary cells (higher NNMT expression detected on BHP 2-7 cell line). |
| IHC | Rabbit polyclonal anti-human NNMT Ab, 1:3000 | PTCs overexpress NNMT, normal tissues and benign thyroid lesions do not express NNMT. | ||
| Xu J et al., 2005 [38] | PTC | In vitro study | BHP 2-7, BHP 7-13, BHP 10-3, BHP 18-21, TPC 1, NPA 87, BHP 5-16, BHP 14-9, BHP 15-3, WRO 82-1, ML-1A, ML-1B, FTC133, FTC238, XTC-1, O4 PC, HX5 PC, Hep G2, LNCaP, MCF-7 cell lines | Higher HNF-1β expression is detected in papillary cell lines with high NNMT activity. |
| Xu J et al., 2006 [40] | PTC | In vitro study | BHP 18-21, BHP 2-7, BHP 14-9, Hep G2 cell lines | The HNF-1β binding site mutation significantly decreases the NNMT promoter activity in BHP 2-7 cells compare to Hep G2 cells. The depsipeptide downregulates NNMT and HNF-1β gene expression in BHP 18-21 cell line. |
| Win T et al., 2013 [33] | NPC | IHC | Mouse monoclonal anti-human NNMT Ab, 1:200 | NNMT overexpression is an independent prognostic factor of worse DSS and MeFS. |
| Pozzi V et al., 2011 [34] | LSCC | In vitro study | KB cell line | KB cells show higher NNMT expression levels compare to mock cell. NNMT levels significantly decreases after silencing. NNMT downregulation significantly reduces the cell proliferation. |
| Cui Y et al., 2019 [13] | ESCC | IHC | Rabbit polyclonal anti-human NNMT Ab, 1:75 | NNMT expression is significantly higher in ESCCs compared to the adjacent normal tissues. NNMT overexpression significantly correlated with lymph node metastasis. |
| In vitro study | EC1, EC9706, TE1, TE13, Eca109 cell lines | EC9706 and TE1 cell lines show highest NNMT expression. NNMT silencing suppresses tumor cells growth, proliferation, and migration. | ||
| Cui Y et al., 2020 [18] | ESCC | In vitro study | EC1, TE1, Eca109 cell lines | NNMT silencing enhances 5-FU inhibitory effect on cell viability and colony formation and increases 5-FU-induced proapoptotic protein levels in the TE1 cells. TE1-siNNMT tumors are significantly smaller and more sensitivity to 5-FU respect to TE1-NC tumors. In TE1-siNNMT tumors, the 5-FU promotes the apoptosis and the tumoral necrosis. |
| Metabolomic study | Gas chromatography-mass spectrometry [Agilent Technologies] (EC1, TE1, Eca109 cell lines) | Nicotinate and nicotinamide metabolism and tricarboxylic acid cycle in TE1 cells are significantly different from those in EC1 and Eca109 cells. |
OSCC: oral squamous cell carcinoma; AdCC: adenoid cystic carcinoma; OMM: oral malignant melanoma; OT: odontogenic tumor; PTC: papillary thyroid carcinoma; NPC: nasopharyngeal carcinoma; LSCC: laryngeal squamous cell carcinoma; ESCC: esophageal squamous cell carcinoma; IHC: immunohistochemistry; DFS: disease-free survival; DSS: disease-specific survival; MeFS: metastasis-free survival; HNF-1β: hepatocyte nuclear factor-1-beta; 5-FU: 5-fluorouracil; NC: negative control; siNNMT: silenced NNMT.