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.
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.
Authors: Salvatore De Maria; Giuseppe Pannone; Pantaleo Bufo; Angela Santoro; Rosario Serpico; Salvatore Metafora; Corrado Rubini; Daniela Pasquali; Silvana M Papagerakis; Stefania Staibano; Gaetano De Rosa; Ernesto Farina; Monica Emanuelli; Andrea Santarelli; Maria Ada Mariggiò; Lucio Lo Russo; Lorenzo Lo Muzio Journal: J Cancer Res Clin Oncol Date: 2008-07-19 Impact factor: 4.553
Authors: Tao Yu; Yong-Tao Wang; Pan Chen; Yu-Hua Li; Yi-Xin Chen; Hang Zeng; Ai-Ming Yu; Min Huang; Hui-Chang Bi Journal: Cell Physiol Biochem Date: 2015-01-28
Authors: E Balducci; M Emanuelli; N Raffaelli; S Ruggieri; A Amici; G Magni; G Orsomando; V Polzonetti; P Natalini Journal: Anal Biochem Date: 1995-06-10 Impact factor: 3.365
Authors: Yongzhi Gao; Matthijs J van Haren; Ed E Moret; Johannes J M Rood; Davide Sartini; Alessia Salvucci; Monica Emanuelli; Pierrick Craveur; Nicolas Babault; Jian Jin; Nathaniel I Martin Journal: J Med Chem Date: 2019-07-12 Impact factor: 7.446