水合黄芩苷通过影响基因组不稳定性和剪接来抑制鼻咽癌的癌症进展。

Baicalin hydrate inhibits cancer progression in nasopharyngeal carcinoma by affecting genome instability and splicing.

作者信息

Lai Weiwei, Jia Jiantao, Yan Bin, Jiang Yiqun, Shi Ying, Chen Ling, Mao Chao, Liu Xiaoli, Tang Haosheng, Gao Menghui, Cao Ya, Liu Shuang, Tao Yongguang

机构信息

Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Xiangya Hospital, Central South University, Changsha, Hunan, China.

Cancer Research Institute, Central South University, Changsha, Hunan, China.

出版信息

Oncotarget. 2017 Dec 4;9(1):901-914. doi: 10.18632/oncotarget.22868. eCollection 2018 Jan 2.

Baicalin hydrate (BH), a natural compound, has been investigated for many years because of its traditional medicinal properties. However, the anti-tumor activities of BH and its epigenetic role in NPC have not been elucidated. In this study, we identified that BH inhibits NPC cell growth and by inducing apoptosis and cell cycle arrest. BH epigenetically regulated genome instability by up-regulating the expression of satellite 2 (Sat2), alpha satellite (α-Sat), and major satellite (Major-Sat). BH also increased the level of IKKα, Suv39H1, and H3K9me3 and decreased LSH expression. Interestingly, BH promoted the splicing of Suv39H1 via the enhancement of m6A RNA methylation, rather than DNA methylation. Taken together, our results demonstrated that BH has an anti-tumor role in NPC and revealed a unique role of BH in genome instability and splicing in response to DNA damage.

水合黄芩苷（BH）是一种天然化合物，因其传统药用特性已被研究多年。然而，BH的抗肿瘤活性及其在鼻咽癌中的表观遗传作用尚未阐明。在本研究中，我们发现BH通过诱导细胞凋亡和细胞周期阻滞来抑制鼻咽癌细胞生长。BH通过上调卫星2（Sat2）、α卫星（α-Sat）和主要卫星（Major-Sat）的表达，在表观遗传上调节基因组不稳定性。BH还增加了IKKα、Suv39H1和H3K9me3的水平，并降低了LSH的表达。有趣的是，BH通过增强m6A RNA甲基化而非DNA甲基化来促进Suv39H1的剪接。综上所述，我们的结果表明BH在鼻咽癌中具有抗肿瘤作用，并揭示了BH在基因组不稳定性和DNA损伤反应中的剪接方面的独特作用。