Department of Biomedical Chemistry, College of Biomedical & Health Science, Konkuk University, Chungju 27478, Chungbuk, Korea.
Department of Food Bioscience, College of Biomedical & Health Science, Konkuk University, Chungju 27478, Chungbuk, Korea.
Int J Mol Sci. 2017 Sep 7;18(9):1924. doi: 10.3390/ijms18091924.
-acetyltransferase 10 (NAT10) has been considered a target for the treatment of human diseases such as cancer and laminopathies; however, its functional role in the biology of melanocytes is questionable. Using a small molecule or small interfering RNA targeting NAT10, we examined the effect of NAT10 inhibition on melanogenesis and melanoma growth in human and mouse melanoma cells. Genetic silencing or chemical inhibition of NAT10 resulted in diminished melanin synthesis through the suppression of melanogenesis-stimulating genes such as those encoding dopachrome tautomerase (DCT) and tyrosinase in B16F10 melanoma cells. In addition, NAT10 inhibition significantly increased cell cycle arrest in S-phase, thereby suppressing the growth and proliferation of malignant melanoma cells in vitro and in vivo. These results demonstrate the potential role of NAT10 in melanogenesis and melanoma growth through the regulation of microphthalmia-associated transcription factor (MITF) expression and provide a promising strategy for the treatment of various skin diseases (melanoma) and pigmentation disorders (chloasma and freckles).
乙酰基转移酶 10（NAT10）已被认为是治疗人类疾病（如癌症和层粘连蛋白病）的靶点；然而，其在黑素细胞生物学中的功能作用仍存在争议。本研究使用针对 NAT10 的小分子或小干扰 RNA，研究了 NAT10 抑制对人源和鼠源黑素瘤细胞中黑素生成和黑色素瘤生长的影响。在 B16F10 黑素瘤细胞中，通过抑制多巴胺醌互变异构酶（DCT）和酪氨酸酶等基因的表达，NAT10 的基因沉默或化学抑制导致黑色素合成减少。此外，NAT10 抑制显著增加了 S 期的细胞周期停滞，从而抑制了体外和体内恶性黑素瘤细胞的生长和增殖。这些结果表明，NAT10 通过调节小眼畸形相关转录因子（MITF）的表达在黑素生成和黑色素瘤生长中发挥作用，并为治疗各种皮肤疾病（黑色素瘤）和色素沉着障碍（黄褐斑和雀斑）提供了有前途的策略。
