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

// Weiwei Lai 1, 2 , Jiantao Jia 1, 2, 4 , Bin Yan 1, 2 , Yiqun Jiang 1, 2 , Ying Shi 1, 2 , Ling Chen 1, 2 , Chao Mao 1, 2 , Xiaoli Liu 1, 2 , Haosheng Tang 1, 2, 3 , Menghui Gao 1, 2, 3 , Ya Cao 1, 2 , Shuang Liu 5 and Yongguang Tao 1, 2, 3 1 Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Xiangya Hospital, Central South University, Changsha, Hunan, China 2 Cancer Research Institute, Central South University, Changsha, Hunan, China 3 Department of Thoracic Surgery, Second Xiangya Hospital, Central South University, Changsha, Hunan, China 4 Changzhi Medical College, Changzhi, Shanxi, China 5 Institute of Medical Sciences, Xiangya Hospital, Central South University, Changsha, Hunan, China Correspondence to: Yongguang Tao, email: taoyong@csu.edu.cn Keywords: baicalin hydrate; genome stability; splicing; DNA methylation; m6A RNA methylation Received: April 19, 2017 Accepted: September 20, 2017 Published: December 04, 2017 ABSTRACT 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 in vivo and in vitro 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.