Nicotinamide N-methyltransferase gene silencing enhances chemosensitivity of melanoma cell lines

Melanoma accounts for less than 5% of all cutaneous neoplasms but is responsible for the greater part of skin cancer-related deaths. Therefore, the identification of molecules that could serve as the therapeutic target is urgent. This study focused on the enzyme nicotinamide N-methyltransferase (NNMT). The effect of NNMT knockdown on cell proliferation and migration of A375 melanoma cells was evaluated by MTT and wound healing assays, respectively. Viability of A375 cells downregulating NNMT was also explored under treatment with dacarbazine, a chemotherapeutic drug approved for advanced melanoma treatment. The impact of enzyme knockdown on cell proliferation and chemosensitivity was also investigated in WM-115 melanoma cells. Results obtained demonstrated that NNMT silencing led to a significant reduction of cell proliferation and migration of A375 cells. Moreover, enzyme downregulation was associated with an increase of melanoma cells sensitivity to treatment with dacarbazine. Analogous effects induced by enzyme knockdown on cell proliferation and chemosensitivity were also found in the WM-115 cell line. Our data seem to demonstrate that NNMT could represent a promising molecular target for the effective treatment of this form of skin cancer.

Automated summary

Melanoma, despite its small proportion of all skin tumors, is a major contributor to skin cancer-related deaths. This study identified NNMT enzyme as a potential therapeutic target for melanoma treatment, demonstrating that reducing NNMT levels can significantly inhibit cell proliferation and migration, as well as enhance sensitivity to chemotherapy drugs in melanoma cells.