LncRNA TMPO-AS1 serves as a ceRNA to promote osteosarcoma tumorigenesis by regulating miR-199a-5p/WNT7B axis
LncRNA TMPO-AS1 serves as a ceRNA to promote osteosarcoma tumorigenesis by regulating miR-199a-5p/WNT7B axis
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DOI：
10.1002/jcb.29451
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发表时间：
2019-11-03
影响因子：
4
通讯作者：
Zhao, Jiang
中科院分区：
文献类型：
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作者：
Cui, Huaan;Zhao, Jiang
骨肉瘤(OS)是一种常见的侵袭性骨肿瘤，多见于儿童和青少年，具有极高的死亡风险。越来越多的研究工作表明，长非编码RNA(LncRNAs)在多种癌症的发生发展中发挥着重要作用。已有研究表明，TMPO-AS1是一种癌基因，但其在OS中的分子机制尚不清楚。我们的研究表明，TMPO-AS1在OS组织和细胞中有显著的过表达。此外，TMPO-AS1缺失抑制了Wnt/β-catenin途径和细胞的增殖，促进了细胞的凋亡。进一步的分子机理研究表明，TMPO-AS1可以与miR-199A-5P发生海绵结合。此外，miR-199a-5p在OS细胞中处于低水平。重要的是，miR-199a-5p的过表达与OS细胞增殖减少、细胞凋亡率增加有关。此外，WNT7B被确认为miR-199a-5p的下游基因。MIR-199a-5p反向调节WNT7B的表达，TMPO-AS1正向调节WNT7B的表达。救助性实验表明，下调的WNT7B可以挽救miR-199a-5p抑制剂介导的对OS进展的抑制，但LiCl2的处理抵消了WNT7B下调的作用。总之，TMPO-AS1通过调节miR-199a-5p/WNT7B轴，作为竞争的内源性RNA促进骨肉瘤的发生，为OS患者提供了潜在的治疗靶点。
Osteosarcoma (OS) is a common kind of aggressive tumor in bone which was mostly identified in children and adolescents with extremely high risk of death. Accumulating research works have displayed that long noncoding RNAs (lncRNAs) exert an essential role in the development of multiple cancers. It has been reported that TMPO-AS1 is an oncogene in cancers; nonetheless, its molecular mechanism in OS is totally unclear. Our present study elucidated that a remarkable overexpression of TMPO-AS1 was found in OS tissues and cells. Moreover, TMPO-AS1 depletion restrained Wnt/beta-catenin pathway and cell proliferation as well as facilitated cell apoptosis. Further molecular mechanism investigations showed that TMPO-AS1 can sponge to miR-199a-5p. Moreover, miR-199a-5p was at a low level at OS cells. Importantly, miR-199a-5p's overexpression was associated with the OS cells' decreased proliferation and increased apoptosis. In addition, WNT7B was confirmed as a downstream gene of miR-199a-5p. Also the WNT7B expression was reversely modulated by miR-199a-5p and positively modulated by TMPO-AS1. Rescue experiments suggested that downregulated WNT7B rescued miR-199a-5p inhibitor-mediated repression on OS progression, but the treatment of LiCl counteracted the effect of WNT7B downregulation. In a word, TMPO-AS1 serves as a competing endogenous RNA to boost osteosarcoma tumorigenesis by regulating miR-199a-5p/WNT7B axis, which provided an underlying therapeutic target for patients with OS.