Department of Clinical Sciences, Polytechnic University of Marche, Via Ranieri 65, 60131, Ancona, Italy.
Department of Clinical and Experimental Medicine, University of Foggia, 71121 - 71122, Foggia, Italy.
Clin Oral Investig. 2019 Feb;23(2):829-838. doi: 10.1007/s00784-018-2497-8. Epub 2018 Jun 7.
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.
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.
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.
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.
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.
口腔鳞状细胞癌（OSCC）是口腔最常见的恶性肿瘤。尽管治疗方法有所进步，但在过去三十年中，口腔癌的 5 年生存率并没有提高。因此，需要新的分子靶点来进行 OSCC 的早期诊断和治疗。在本研究中，我们专注于酶烟酰胺 N-甲基转移酶（NNMT）。我们之前已经表明，该酶在 OSCC 中表达上调，并且在 PE/CA PJ-15 细胞中敲低 NNMT 显着降低了体外细胞生长和体内肿瘤形成能力。
为了进一步探讨该酶在口腔癌细胞代谢中的作用，将 NNMT 表达载体（pcDNA3-NNMT）转染 HSC-2 细胞，并通过 MTT 测定评估酶上调对细胞增殖的影响。随后，我们通过实时 PCR 研究了 NNMT 对细胞凋亡和增殖的分子作用，以探索 β-连环蛋白、生存素和 Ki-67 的表达。此外，我们对 20 例 OSCC 组织样本进行了免疫组织化学染色，以探索 NNMT 和生存素ΔEx3 同种型的表达水平。
酶上调显着增加了体外细胞生长。此外，在 HSC-2 细胞和 OSCC 组织样本中均发现 NNMT 与生存素ΔEx3 同种型表达水平之间存在正相关。
总之，我们的结果表明 NNMT 可能参与 OSCC 细胞的增殖和致瘤能力，并且似乎表明该酶可能是治疗口腔癌的潜在靶标。
NNMT 参与细胞生长和抗凋亡机制，似乎表明该酶可能是改善 OSCC 患者生存的新治疗靶标。
