Department of Radiotherapy, China-Japan Union Hospital of Jilin University, Changchun 130033, PR China.
Department of gastroenterology, The First Hospital of Jilin University, Changchun 130021, PR China.
Biomed Pharmacother. 2018 Jan;97:136-142. doi: 10.1016/j.biopha.2017.10.074. Epub 2017 Nov 6.
Accumulating evidence indicates that long noncoding RNAs (LncRNAs) are involved in tumorigenesis and tumor development. LncRNA GACAT3 (GACAT3) has been reported to be upregulated in gastric cancer (GC); however, the biological function and underlying mechanisms of GACAT3 remain largely unknown. Here, we found that GACAT3 showed a higher expression in GC tissues and cell lines. Increased GACAT3 level was significantly associated with a shorter overall survival of patients with GC. Functionally, we demonstrated that knockdown of GACAT3 significantly inhibited proliferation, colony formation, migration, and invasion of GC cells in vitro. Moreover, underexpression of GACAT3 decreased tumorigenesis in vivo. Mechanistically, we proved that GACAT3 directly binds to microRNA-497 (miR-497), and GACAT3 expression was inversely correlated with miR-497 expression. Taken together, we demonstrate that GACAT3 may function as an oncogene that promotes GC progression, and may serve as a potential target for GC therapy in the future.
越来越多的证据表明，长非编码 RNA（lncRNA）参与肿瘤的发生和发展。已有研究报道，lncRNA GACAT3（GACAT3）在胃癌（GC）中上调；然而，GACAT3 的生物学功能和潜在机制在很大程度上仍不清楚。在这里，我们发现 GACAT3 在 GC 组织和细胞系中表达升高。GACAT3 水平的升高与 GC 患者总生存期的缩短显著相关。功能上，我们证明了敲低 GACAT3 可显著抑制 GC 细胞的体外增殖、集落形成、迁移和侵袭。此外，GACAT3 的低表达降低了体内的肿瘤发生。机制上，我们证明了 GACAT3 可以直接与 microRNA-497（miR-497）结合，并且 GACAT3 的表达与 miR-497 的表达呈负相关。综上所述，我们证明 GACAT3 可能作为一种癌基因促进 GC 的进展，并且可能成为未来 GC 治疗的潜在靶点。
