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Nicotinamide N-methyltransferase gene silencing enhances chemosensitivity of melanoma cell lines
Pigment Cell & Melanoma Research ( IF 4.3 ) Pub Date : 2021-05-21 , DOI: 10.1111/pcmr.12993
Roberto Campagna 1 , Eleonora Salvolini 1 , Veronica Pompei 1 , Valentina Pozzi 1 , Alessia Salvucci 1 , Elisa Molinelli 2 , Valerio Brisigotti 2 , Davide Sartini 1 , Anna Campanati 2 , Annamaria Offidani 2 , Monica Emanuelli 1, 3
Affiliation  

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.

中文翻译:

烟酰胺 N- 甲基转移酶基因沉默增强黑色素瘤细胞系的化学敏感性

黑色素瘤占所有皮肤肿瘤的比例不到 5%,但却是导致皮肤癌相关死亡的大部分原因。因此,迫切需要鉴定可作为治疗靶点的分子。本研究的重点是烟酰胺 N-甲基转移酶 (NNMT)。分别通过 MTT 和伤口愈合试验评估 NNMT 敲低对 A375 黑色素瘤细胞的细胞增殖和迁移的影响。A375 细胞下调 NNMT 的活力也在用达卡巴嗪治疗下进行了探索,达卡巴嗪是一种被批准用于晚期黑色素瘤治疗的化疗药物。还在 WM-115 黑色素瘤细胞中研究了酶敲低对细胞增殖和化学敏感性的影响。获得的结果表明,NNMT 沉默导致 A375 细胞的细胞增殖和迁移显着减少。此外,酶下调与黑色素瘤细胞对达卡巴嗪治疗的敏感性增加有关。在 WM-115 细胞系中也发现了酶敲低对细胞增殖和化学敏感性的类似影响。我们的数据似乎表明,NNMT 可以代表有效治疗这种皮肤癌的有希望的分子靶点。
更新日期:2021-05-21
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