lncRNA ZMIZ1-AS1通过稳定ZMIZ1促进骨肉瘤进展  

Long non-coding RNA ZMIZ1-AS1 promotes osteosarcoma progression by stabilization of ZMIZ1

作　　者：周逸驰 黎清波 蔡磊 周传坤 王正坤 寇博文 刘伟军 ZHOU Yichi;LI Qingbo;CAI Lei;ZHOU Chuankun;WANG Zhengkun;KOU Bowen;LIU Weijun(Wuhan Fourth Hospital,Hubei Wuhan 430000,China)

机构地区：[1]武汉市第四医院,湖北武汉430000

出　　处：《现代肿瘤医学》2024年第3期412-419,共8页Journal of Modern Oncology

基　　金：职业病危害识别与控制湖北省重点实验室开放基金项目(编号:OHIC2020Z12);湖北省武汉市卫健委医学科研面上项目(编号:WX21D83)。

摘　　要：目的:探讨ZMIZ1-AS1及其下游通路在骨肉瘤进展中的作用。方法:通过克隆形成试验、Transwell细胞侵袭试验和划痕试验检测骨肉瘤细胞增殖、侵袭及迁移能力,染色质免疫沉淀法及双荧光素酶报告法检测SOX2及MYC蛋白与ZMIZ1-AS1启动子的结合,RNA免疫沉淀法检测PTBP1蛋白与ZMIZ1-AS1(或ZMIZ1 mRNA)的相互作用。结果:SOX2和MYC是Hippo通路的下游效应子,并可转录激活ZMIZ1-AS1;与对照组相比,骨肉瘤组织与细胞中ZMIZ1-AS1表达量较高,沉默ZMIZ1-AS1能抑制骨肉瘤细胞活性、增殖、迁移及侵袭;ZMIZ1-AS1募集RNA结合蛋白PTBP1来稳定ZMIZ1 mRNA;PTBP1或ZMIZ1过表达可挽救沉默ZMIZ1-AS1对骨肉瘤细胞过程的抑制作用。结论:ZMIZ1-AS1通过稳定ZMIZ1促进骨肉瘤进展。Objective:To explore the role of ZMIZ1-AS1 and its downstream signaling pathway in the progression of osteosarcoma(OS).Methods:Cell proliferation,invasion,and migration were detected by colony formation,Transwell,and wound healing assays.The binding of SOX2 or MYC protein with ZMIZ1-AS1 promoter was explored by ChIP assay and dual-luciferase reporter assay.Interaction between PTBP1 protein and ZMIZ1-AS1(or ZMIZ1 mRNA)was detected by RIP assay.Results:SOX2 and MYC are the downstream effectors of the Hippo pathway and transcriptionally activated ZMIZ1-AS1.Compared with the controls,OS tissues and cells contained higher ZMIZ1-AS1 expression.Silencing of ZMIZ1-AS1 repressed OS cell viability,proliferation,migration,and invasion.Our findings further showed that ZMIZ1-AS1 recruits RNA-binding protein PTBP1 to stabilize ZMIZ1 mRNA.PTBP1 or ZMIZ1 overexpression rescues the suppressive effects of silenced ZMIZ1-AS1 on OS cellular processes.Importantly,ZMIZ1-AS1 promotes OS growth in vivo by stabilization of ZMIZ1.Conclusion:Long non-coding RNA ZMIZ1-AS1 promotes OS progression by stabilization of ZMIZ1.

关 键 词：长链非编码RNA ZMIZ1-AS1 骨肉瘤 

分 类 号：R738.1[医药卫生—肿瘤]