Hou Guiqin, Zhao Qi, Zhang Mengying, Wang Peng, Ye Hua, Wang Yang, Ren Yandan, Zhang Jianying, Lu Zhaoming
School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, People's Republic of China.
College of Public Health, Zhengzhou University, Zhengzhou, People's Republic of China.
Onco Targets Ther. 2019 Jul 2;12:5215-5225. doi: 10.2147/OTT.S207238. eCollection 2019.
The aberrant activation of Lysine-specific demethylase 1(LSD1), Notch and PI3K/Akt/mTOR signaling pathways were frequently happened in many cancers, including esophageal squamous cell carcinoma (ESCC). However, the regulatory relationship between LSD1 and Notch as well as PI3K/Akt/mTOR pathways is still unclear. This study aimed to explore the regulatory effects and mechanisms of LSD1 on Notch and PI3K/Akt/mTOR pathway in ESCC. Firstly, we demonstrated that LSD1 and proteins in Notch and PI3K/Akt/mTOR pathway were expressed in ESCC cells. Secondly, inhibition of LSD1 by tranylcypromine (TCP) or shRNA could decrease the expressions of related proteins in Notch and PI3K/Akt/mTOR signaling pathways in ESCC cells. Finally, we found that LSD1 could bind to the promoter regions of Notch3, Hes1 and CR2, and the combinations between them were reduced by TCP in ESCC. Summarily, this study indicated that LSD1 might positively regulate Notch and PI3K/Akt/mTOR pathways through binding the promoter regions of related genes in Notch pathway in ESCC.
赖氨酸特异性去甲基化酶1（LSD1）、Notch和PI3K/Akt/mTOR信号通路的异常激活在包括食管鳞状细胞癌（ESCC）在内的许多癌症中经常发生。然而，LSD1与Notch以及PI3K/Akt/mTOR通路之间的调控关系仍不清楚。本研究旨在探讨LSD1对ESCC中Notch和PI3K/Akt/mTOR通路的调控作用及机制。首先，我们证明了LSD1以及Notch和PI3K/Akt/mTOR通路中的蛋白在ESCC细胞中表达。其次，反苯环丙胺（TCP）或短发夹RNA（shRNA）对LSD1的抑制可降低ESCC细胞中Notch和PI3K/Akt/mTOR信号通路中相关蛋白的表达。最后，我们发现LSD1可与Notch3、Hes1和CR2的启动子区域结合，在ESCC中TCP可减少它们之间的结合。总之，本研究表明LSD1可能通过结合ESCC中Notch通路相关基因的启动子区域来正向调控Notch和PI3K/Akt/mTOR通路。
