标题：Melatonin Inhibits Glioblastoma Stem-like cells through Suppression of EZH2-NOTCHI Signaling Axis
作者：Zheng, Xiangrong; Pang, Bo; Gu, Guangyan; Gao, Taihong; Zhang, Rui; Pang, Qi; Liu, Qian
作者机构：[Zheng, Xiangrong; Gao, Taihong; Zhang, Rui; Pang, Qi] Shandong Univ, Dept Neurosurg, Shandong Prov Hosp, 324 Jingwu Rd, Jinan 250021, Shandong, Peopl 更多
通讯作者：Pang, Q;Liu, Q
通讯作者地址：[Pang, Q]Shandong Univ, Dept Neurosurg, Shandong Prov Hosp, 324 Jingwu Rd, Jinan 250021, Shandong, Peoples R China;[Liu, Q]Shandong Univ, Dept Histol 更多
来源：INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
关键词：Melatonin; Glioblastoma stem-like cells; viability; self-renewal; EZH2;; NOTCH1
摘要：Glioblastoma stem-like cells (GSCs) play essential roles in glioma growth, radio-and chemo-resistance, and recurrence. Elimination of GSCs has therefore become a key strategy and challenge in glioblastoma therapy. Here, we show that melatonin, an indolamine derived from I-tryptophan, significantly inhibited viability and self-renewal ability of GSCs accompanied by a decrease of stem cell markers. We have identified EZH2-NOTCH1 signaling as the key signal pathway that regulated the effects of melatonin in the GSCs. Instead of transcriptionally silencing gene expression by generating a methylated epigenetic mark at histone 3 at lysine 27 (H3K27), EZH2 regulates NOTCH1 expression by directly binding to the NOTCH1 promoter. Moreover, correlation between the expressions of EZH2 and NOTCH intracellular domain 1 (NICD1) was observed in the clinical tumor samples, evidently supporting the existence of EZH2-NOTCH1 interaction in the gliomas and GSCs. Collectively, we demonstrated that melatonin, a potential tumor inhibitor, performs its function partly by suppressing GSC properties through EZH2-NOTCH1 signaling axis.