Renji Hospital Affiliated to Medical College of Shanghai Jiaotong University, Shanghai, 200025, China.
Cell Death Dis. 2021 Apr 6;12(4):349. doi: 10.1038/s41419-021-03571-5.
Gastric cancer (GC) is a common type of tumor that is characterized with high metastatic rate. In recent years, increasing studies have indicated that lncRNAs are involved in the regulation on cancer cell proliferation and migration. However, the functional role of long intergenic non-protein coding RNA 1559 (LINC01559) in GC is still unclear. In this study, we applied quantitative real-time polymerase chain reaction (RT-qPCR) and examined that LINC01559 expression was significantly enhanced in GC cells. Functional assays such as EdU, colony formation, JC-1 and transwell assays displayed that silencing LINC01559 inhibited cell proliferation and migration while promoted cell apoptosis in GC. Besides, western blot analysis and immunofluorescence assays examined the expression of factors related to epithelial-mesenchymal transition (EMT) and indicated that EMT process was blocked by LINC01559 knockdown in GC cells. Besides, LINC01559 silencing inhibited tumor growth in vivo. In addition, Chromatin immunoprecipitation (ChIP) assays demonstrated that zinc finger E-box binding homeobox 1 (ZEB1) served as a transcription factor to combine with LINC01559 promoter and activated the expression of LINC01559 in GC cells. In return, LINC01559 recruited insulin like growth factor 2 mRNA binding protein 2 (IGF2BP2) to stabilize ZEB1 mRNA to up-regulate ZEB1 in GC cells. In short, the findings in this research might provide a novel target for GC treatment.
胃癌（GC）是一种常见的肿瘤，其特征是转移率高。近年来，越来越多的研究表明 lncRNA 参与了癌细胞增殖和迁移的调控。然而，长链非编码 RNA 1559（LINC01559）在 GC 中的功能作用尚不清楚。在本研究中，我们应用实时定量聚合酶链反应（RT-qPCR）并检测到 GC 细胞中 LINC01559 的表达明显增强。EdU、集落形成、JC-1 和 Transwell 检测等功能实验显示，沉默 LINC01559 抑制 GC 细胞的增殖和迁移，同时促进细胞凋亡。此外，Western blot 分析和免疫荧光分析检测到与上皮-间充质转化（EMT）相关的因子表达，表明 LINC01559 敲低可阻断 GC 细胞中的 EMT 过程。此外，LINC01559 沉默抑制体内肿瘤生长。此外，染色质免疫沉淀（ChIP）实验表明，锌指 E 盒结合同源盒 1（ZEB1）作为转录因子与 LINC01559 启动子结合并激活 GC 细胞中 LINC01559 的表达。反过来，LINC01559 招募胰岛素样生长因子 2 mRNA 结合蛋白 2（IGF2BP2）稳定 ZEB1 mRNA，以上调 GC 细胞中的 ZEB1。总之，本研究的结果可能为 GC 的治疗提供一个新的靶点。
