Cell Biology and Toxicology ( IF 5.3 ) Pub Date : 2022-06-08 , DOI: 10.1007/s10565-022-09728-y Qiang Wang 1 , Chunmei Zhang 2 , Shengya Cao 3 , Hongying Zhao 4 , Rongke Jiang 5 , Yanfang Li 4
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It has been manifested that tumor-derived exosomes (Exos) can deliver long noncoding RNAs to participate in gastric cancer (GC) progression. In this research, we intended to dissect out whether tumor-derived Exos carried LINC01091 to afflict the growth and metastasis of GC. GC tissues and human GC cells were attained for RNA and protein quantification. Accordingly, LINC01091, ELF4, and CDX2 were abundant but microRNA (miR)-128-3p was underexpressed in GC tissues and cells. Exos were isolated from LINC01091-silenced GC cells (Exo-sh-LINC01091). GC cells were co-cultured with Exo-sh-LINC01091 or manipulated with miR mimic, inhibitor, or overexpressing or silencing plasmids. Exo-sh-LINC01091, LINC01091, ELF4 or CDX2 silencing, or miR-128-3p upregulation augmented GC cell proliferative, migrating, and invasive properties. In addition, luciferase, RNA pull-down, and ChIP assays offered evidence supporting the mechanism that LINC01091 bound to miR-128-3p that inversely targeted ELF4, and ELF4 transcriptionally activated CDX2 by binding to its promoter in GC cells. Moreover, Exo-sh-LINC01091 modulated the miR-128-3p/ELF4/CDX2 axis and restrained the tumorigenesis and metastasis in vivo. Conclusively, LINC01091 shuttled by tumor-derived Exos might expedite GC development by activating the ELF4/CDX2 axis via miR-128-3p downregulation.
Graphical abstract
中文翻译：
肿瘤来源的外泌体协调 microRNA-128-3p/ELF4/CDX2 轴，通过递送 LINC01091 促进胃癌的生长和转移
已经表明，肿瘤来源的外泌体 (Exos) 可以递送长链非编码 RNA 以参与胃癌 (GC) 的进展。在这项研究中，我们打算剖析肿瘤来源的 Exos 是否携带 LINC01091 来影响 GC 的生长和转移。获得 GC 组织和人类 GC 细胞用于 RNA 和蛋白质定量。因此，LINC01091、ELF4和CDX2丰富，但 microRNA (miR)-128-3p 在 GC 组织和细胞中表达不足。Exos 是从 LINC01091 沉默的 GC 细胞 (Exo-sh-LINC01091) 中分离出来的。GC 细胞与 Exo-sh-LINC01091 共培养，或用 miR 模拟物、抑制剂或过表达或沉默质粒进行操作。Exo-sh-LINC01091、LINC01091、ELF4或CDX2沉默或 miR-128-3p 上调增强了 GC 细胞的增殖、迁移和侵袭特性。此外，荧光素酶、RNA pull-down 和 ChIP 分析提供的证据支持 LINC01091 结合反向靶向ELF4的 miR-128-3p 的机制，并且ELF4通过结合 GC 细胞中的启动子转录激活CDX2 。此外，Exo-sh-LINC01091 调节 miR-128-3p/ ELF4 / CDX2轴并抑制体内肿瘤发生和转移。最后，由肿瘤来源的 Exos 穿梭的 LINC01091 可能通过 miR-128-3p 下调激活ELF4 / CDX2轴来加速 GC 的发展。
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