近年来,组蛋白甲基转移酶(HMT)由于其致癌作用已成为癌症的重要治疗靶标。在这里,我们使用GLP/G9a抑制剂UNC0646来评估抑制此类HMT是否可以诱导MeWo黑色素瘤细胞死亡.此外,我们研究了与观察到的细胞死亡事件有关的细胞和分子机制.最后,我们对480份黑色素瘤样本进行了功能基因组学分析,以确定G9a/GLP参与黑色素瘤的特征.有趣的是,在UNC0646治疗后,MeWo细胞发生凋亡,其次是线粒体膜电位的丧失和活性氧(ROS)的产生。此外,用UNC0646处理的MeWo细胞显示细胞周期停滞和增殖抑制。在分子水平上,UNC0646处理增加了CDK1和BAX的转录水平,BCL-2mRNA水平降低。最后,我们进行了功能富集分析,这表明,根据GLP和G9a表达,黑色素瘤样品中富集了数十种生物学途径,包括凋亡和坏死。一起来看,我们的数据显示,使用UNC0646抑制GLP/G9a通过控制黑色素瘤细胞的增殖和诱导细胞凋亡发挥抗癌作用.
In recent years, histone methyltransferases (HMTs) have emerged as important therapeutic targets in cancer due to their oncogenic role. Herein, we used the
GLP/G9a inhibitor UNC0646 to assess whether the inhibition of such HMTs could induce cell death in MeWo melanoma cells. Furthermore, we investigated the cellular and molecular mechanisms involved in the observed cell death events. Finally, we performed a functional genomics analysis of 480 melanoma samples to characterize G9a/
GLP involvement in melanoma. Interestingly, after UNC0646 treatment, MeWo cells underwent apoptosis, followed by loss of mitochondrial membrane potential and the generation of reactive oxygen species (ROS). Furthermore, MeWo cells treated with UNC0646 showed cell cycle arrest and inhibition of proliferation. At the molecular level, UNC0646 treatment increased the transcriptional levels of CDK1 and BAX, and decreased BCL-2 mRNA levels. Finally, we performed a functional enrichment analysis, which demonstrated that dozens of biological pathways were enriched in melanoma samples according to
GLP and G9a expression, including apoptosis and necrosis. Taken together, our data show that inhibition of
GLP/G9a using UNC0646 exerts anticancer effects on melanoma cells by controlling their proliferation and inducing apoptosis.