长链非编码 RNA B4GALT1-AS1 通过招募 HuR 增强 YAP 转录活性促进骨肉瘤细胞干性和迁移。
LncRNA B4GALT1-AS1 recruits HuR to promote osteosarcoma cells stemness and migration via enhancing YAP transcriptional activity.
机构信息
School of Medicine, TongRen Hospital, Shanghai JiaoTong University, Shanghai, China.
出版信息
Cell Prolif. 2018 Dec;51(6):e12504. doi: 10.1111/cpr.12504. Epub 2018 Sep 4.
Abstract
OBJECTIVES
This study aims to reveal the roles and related mechanisms of LncRNA B4GALT1-AS1 in osteosarcoma (OS) cells stemness and migration.
MATERIALS AND METHODS
Real-time quantitative PCR (RT-qPCR) was used to detect the expression of several LncRNAs in OS tissues and normal adjacent tissues and in OS mammospheres and cells. Cell viability, transwell migration, tumour spheres formation and in vivo tumour formation assays were used to examine the effects of LncRNA B4GALT1-AS1 on OS progression. In addition, RNA immunoprecipitation (RIP) and Luciferase reporter assays were performed to determine the binding site of RNA-binding protein HuR on B4GALT1-AS1 and transcriptional factor YAP. Immunofluorescence analysis was used to examine YAP nuclear-cytoplasm translocation.
RESULTS
LncRNA B4GALT1-AS1 expression was significantly increased in OS tissues and cells spheres. Knockdown of B4GALT1-AS1 inhibited OS cells proliferation, migration, stemness and chemotherapeutic sensitivity. Mechanistically, B4GALT1-AS1 recruited HuR to enhance YAP mRNA stability and thus its transcriptional activity.
CONCLUSIONS
We indicate that lncRNA B4GALT1-AS1 promotes OS cells stemness and migration via recruiting HuR to enhance YAP activity.
摘要
目的
本研究旨在揭示 LncRNA B4GALT1-AS1 在骨肉瘤（OS）细胞干性和迁移中的作用及相关机制。
材料与方法
实时定量 PCR（RT-qPCR）用于检测 OS 组织和正常相邻组织以及 OS 类器官和细胞中几种 LncRNA 的表达。细胞活力、Transwell 迁移、肿瘤球体形成和体内肿瘤形成实验用于研究 LncRNA B4GALT1-AS1 对 OS 进展的影响。此外，进行 RNA 免疫沉淀（RIP）和荧光素酶报告基因实验以确定 RNA 结合蛋白 HuR 与 B4GALT1-AS1 及转录因子 YAP 的结合位点。免疫荧光分析用于检测 YAP 的核质转位。
结果
LncRNA B4GALT1-AS1 在 OS 组织和细胞球体中表达显著增加。B4GALT1-AS1 敲低抑制 OS 细胞增殖、迁移、干性和化疗敏感性。机制上，B4GALT1-AS1 招募 HuR 增强 YAP mRNA 稳定性，从而增强其转录活性。
结论
我们表明，LncRNA B4GALT1-AS1 通过招募 HuR 增强 YAP 活性促进 OS 细胞干性和迁移。
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