Jiangxi Provincial Key Laboratory of Tumor Metastasis and Precision Therapy, Center Laboratory, The Third Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, PR China.
Department of Ophthalmology, The Third Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, PR China.
Invest Ophthalmol Vis Sci. 2022 Mar 2;63(3):20. doi: 10.1167/iovs.63.3.20.
To study the role of lysine-specific demethylase 1 (LSD1) in retinoblastoma (RB) growth and to determine whether the LSD1 inhibitor SP2509 can inhibit RB progression.
We detected the levels of LSD1 in 12 RB tissue samples, two RB cell lines (Y79 and Weri-RB1), and a retinal pigment epithelium cell line (ARPE-19). Overexpression or knockdown of LSD1 was performed to examine the role of LSD1 in RB cancer cell survival. In vitro and in vivo experiments were conducted to detect the antitumor effect of SP2509, and the antitumor mechanism of SP2509 was examined by RNA sequencing and Western blot.
LSD1 is overexpressed in RB tissues and cells and increases RB cancer cell viability and colony formation ability. The LSD1 inhibitor SP2509 inhibits RB cell proliferation in vitro and in vivo. Treatment with SP2509 increases the levels of dimethylated histone 3 lysine 4 (H3K4me2) and inhibits the expression of β-catenin signaling pathway-related proteins in RB cells.
We demonstrated that LSD1 is overexpressed in RB cells and promotes RB cell survival. The LSD1 inhibitor SP2509 exerted strong growth inhibition in vitro and in vivo, which was at least partially mediated by suppression of the β-catenin pathway.
研究赖氨酸特异性脱甲基酶 1（LSD1）在视网膜母细胞瘤（RB）生长中的作用，并确定 LSD1 抑制剂 SP2509 是否能抑制 RB 进展。
我们检测了 12 个 RB 组织样本、两个 RB 细胞系（Y79 和 Weri-RB1）和一个视网膜色素上皮细胞系（ARPE-19）中 LSD1 的水平。通过过表达或敲低 LSD1 来研究 LSD1 在 RB 癌细胞存活中的作用。进行体外和体内实验来检测 SP2509 的抗肿瘤作用，并通过 RNA 测序和 Western blot 来研究 SP2509 的抗肿瘤机制。
LSD1 在 RB 组织和细胞中过表达，增加了 RB 癌细胞的活力和集落形成能力。LSD1 抑制剂 SP2509 抑制 RB 细胞在体外和体内的增殖。SP2509 处理增加了组蛋白 3 赖氨酸 4 二甲基化（H3K4me2）的水平，并抑制了 RB 细胞中β-连环蛋白信号通路相关蛋白的表达。
我们证明 LSD1 在 RB 细胞中过表达，并促进 RB 细胞存活。LSD1 抑制剂 SP2509 在体外和体内均表现出强烈的生长抑制作用，至少部分是通过抑制β-连环蛋白通路介导的。
