Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Department of Emergency, Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Cell Death Dis. 2019 Jan 25;10(2):70. doi: 10.1038/s41419-019-1344-4.
Accumulating evidence have suggested that long noncoding RNAs (lncRNAs) are known to regulate diverse tumorigenic processes. Recently, a novel lncRNA LINC01939 was underexpressed and emerged as a tumor suppressive lncRNA in gastric cancer (GC). In this study, we aimed to investigate the biological function and molecular mechanism of LINC01939 in GC. We found that LINC01939 expression was significantly downregulated in GC tissues and cell lines. Low expression of LINC01939 was correlated with tumor metastasis and shorter survival in GC patients. Functionally, LINC01939 overexpression remarkably inhibited the invasion and migration of GC cells in vitro and in vivo. Mechanistically, LINC01939 regulated the expression of early growth response 2 (EGR2) protein by competitively binding to miR-17-5p. Upregulation of miR-17-5p reversed GC metastasis and EMT process caused by LINC01939 by rescue analysis. Taken together, these results suggested that LINC01939 repressed GC invasion and migration by functioning as a ceRNA for miR-17-5p to regulate EGR2 expression. Our findings provided a novel prognostic marker and therapeutic target for GC patients.
越来越多的证据表明，长非编码 RNA（lncRNA）已知可以调节多种肿瘤发生过程。最近，一种新型的 lncRNA LINC01939 在胃癌（GC）中表达下调，并作为一种肿瘤抑制性 lncRNA 出现。在本研究中，我们旨在研究 LINC01939 在 GC 中的生物学功能和分子机制。我们发现 LINC01939 在 GC 组织和细胞系中的表达显著下调。LINC01939 表达水平低与 GC 患者的肿瘤转移和生存时间缩短相关。功能上，LINC01939 过表达可显著抑制 GC 细胞的体外和体内侵袭和迁移。机制上，LINC01939 通过竞争性结合 miR-17-5p 来调节早期生长反应因子 2（EGR2）蛋白的表达。miR-17-5p 的上调通过挽救分析逆转了 LINC01939 引起的 GC 转移和 EMT 过程。综上所述，这些结果表明，LINC01939 通过作为 miR-17-5p 的 ceRNA 来调节 EGR2 表达，从而抑制 GC 的侵袭和迁移。我们的研究结果为 GC 患者提供了一种新的预后标志物和治疗靶点。
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