Miao Yingying, Liu Guifeng, Liu Lin
Department of Anesthesiology, Union Hospital of Jilin University, Changchun, 130033, People's Republic of China.
Department of Radiology, Union Hospital of Jilin University, No. 126, Xiantai Street, Changchun, 130033, Jilin, People's Republic of China.
Cancer Cell Int. 2021 Jan 4;21(1):2. doi: 10.1186/s12935-020-01636-7.
Osteosarcoma (OS) is a malignant tumor characterized by the direct production of bone or osteoid tissues by proliferating tumor cells. Suppressor of variegation 3-9 homolog 2 (SUV39H2) is implicated in the occurrence of OS. Therefore, we designed this study to investigate effects of SUV39H2 in OS meditated by the lysine specific demethylase-1/E-cadherin (LSD1/CDH1) axis.
Clinical OS tissues and paracancerous tissues were collected for analysis of SUV39H2, LSD1 and CDH1 expression, and Kaplan-Meier survival analysis was applied to test the relationship between SUV39H2 expression and overall survival. Loss- and gain-of-function assays were conducted to determine the roles of SUV39H2, LSD1 and CDH1 in OS epithelial mesenchymal transition (EMT) and migration in OS cells, with quantitation of relevant proteins by immunofluorescence. We confirmed the effects of modulating the SUV39H2/CDH1 axis in a mouse OS tumor model.
SUV39H2 and LSD1 were highly expressed, while CDH1 was downregulated in OS tissues and cells. SUV39H2 expression correlated inversely with overall survival of patients with OS. SUV39H2 positively regulated LSD1 expression, while LSD1 negatively regulated CDH1 expression. SUV39H2 or LSD1 overexpression, or CDH1 silencing promoted migration and EMT, as indicated by reduced E-cadherin and dramatically upregulated Vimentin and N-cadherin of OS cells. SUV39H2 expedited the progression of OS, which was reversed by CDH1 repression in the setting of OS in vitro and in vivo.
Collectively, our results demonstrate highly expressed SUV39H2 in OS elevates the expression of LSD1 to downregulate CDH1 expression, thereby aggravating OS, providing a potential therapeutic target for treatment of OS.
骨肉瘤（OS）是一种恶性肿瘤，其特征是增殖的肿瘤细胞直接产生骨或类骨组织。异染色质蛋白3-9同源物2（SUV39H2）与骨肉瘤的发生有关。因此，我们设计了本研究，以探讨SUV39H2在赖氨酸特异性去甲基化酶-1/E-钙黏蛋白（LSD1/CDH1）轴介导的骨肉瘤中的作用。
收集骨肉瘤临床组织和癌旁组织，分析SUV39H2、LSD1和CDH1的表达，并采用Kaplan-Meier生存分析来检验SUV39H2表达与总生存期之间的关系。进行功能缺失和功能获得实验，以确定SUV39H2、LSD1和CDH1在骨肉瘤上皮-间质转化（EMT）和骨肉瘤细胞迁移中的作用，并通过免疫荧光对相关蛋白进行定量分析。我们在小鼠骨肉瘤肿瘤模型中证实了调节SUV39H2/CDH1轴的作用。
SUV39H2和LSD1在骨肉瘤组织和细胞中高表达，而CDH1表达下调。SUV39H2表达与骨肉瘤患者的总生存期呈负相关。SUV39H2正向调节LSD1表达，而LSD1负向调节CDH1表达。SUV39H2或LSD1过表达，或CDH1沉默促进了迁移和EMT，表现为骨肉瘤细胞中E-钙黏蛋白减少，波形蛋白和N-钙黏蛋白显著上调。SUV39H2加速了骨肉瘤的进展，在体外和体内骨肉瘤环境中，CDH1抑制可逆转这一过程。
总体而言，我们的结果表明，骨肉瘤中高表达的SUV39H2提高了LSD1的表达，从而下调CDH1表达，进而加重骨肉瘤，为骨肉瘤的治疗提供了一个潜在的治疗靶点。
