Nicotinamide N-methyltransferase gene silencing enhances chemosensitivity of melanoma cell lines
Nicotinamide N-methyltransferase gene silencing enhances chemosensitivity of melanoma cell lines
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DOI：
10.1111/pcmr.12993
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发表时间：
2021-05-28
影响因子：
4.3
通讯作者：
Emanuelli, Monica
中科院分区：
文献类型：
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作者：
Campagna, Roberto;Salvolini, Eleonora;Emanuelli, Monica
黑色素瘤在所有皮肤肿瘤中所占比例不到5%，但却导致了大部分皮肤癌相关死亡。因此，鉴定可作为治疗靶点的分子迫在眉睫。本研究的重点是烟酰胺n -甲基转移酶（NNMT）。NNMT敲除对A375黑色素瘤细胞增殖和迁移的影响分别通过MTT和伤口愈合试验进行评估。在达卡巴嗪（一种被批准用于晚期黑色素瘤治疗的化疗药物）治疗下，研究人员还探索了下调NNMT的A375细胞的活力。在WM-115黑色素瘤细胞中也研究了酶敲低对细胞增殖和化学敏感性的影响。结果表明，NNMT沉默导致A375细胞的增殖和迁移显著减少。此外，酶下调与黑素瘤细胞对达卡巴嗪治疗的敏感性增加有关。在WM-115细胞系中也发现了类似的酶敲低对细胞增殖和化学敏感性的影响。我们的数据似乎表明，NNMT可能是有效治疗这种皮肤癌的一个有希望的分子靶点。
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.