Department of Gastroenterology, The Third Affiliated Hospital of Qiqihar Medical University, Qiqihar, 161000, China.
Department of Gastroenterology, The Third Affiliated Hospital of Qiqihar Medical University, Qiqihar, 161000, China.
Biochem Biophys Res Commun. 2019 Apr 16;511(4):926-930. doi: 10.1016/j.bbrc.2019.03.010. Epub 2019 Mar 8.
Gastric cancer (GC) is one of the most common malignancies of digestive system with aggressive phenotypes. Circular RNAs (circRNAs) play a pivotal function in cancer initiation and development. Nevertheless, the function and mechanism of circRNAs in gastric cancer (GC) is not fully understood. We found circ-ERBB2 was strikingly increased in GC tissues and cells. Noticeably, circ-ERBB2 upregulation in tumorous tissues was linked to patients' tumor size, depth of invasion, and overall survival. A series of gain and loss-of-function assays indicated its oncogenic role in GC cells, including cell proliferation, apoptosis, migration and invasion. We further predicted and identified circ-ERBB2 sponged miR-503 and miR-637 by bioinformatics analysis and luciferase reporter system. CACUL1 and MMP-19 were then predicted and confirmed as the target of miR-503 and miR-637, respectively. Furthermore, rescue assays indicated that circ-ERBB2 promoted tumor growth and invasion via miR-503/CACUL1 and miR-637/MMP-19 pathways, respectively. In summary, these findings demonstrated that circ-ERBB2 functions as an oncogene in GC and might be useful in developing promising therapies for this fatal malignancy.
胃癌（GC）是消化系统最常见的恶性肿瘤之一，具有侵袭性表型。环状 RNA（circRNAs）在癌症的发生和发展中起着关键作用。然而，circRNAs 在胃癌（GC）中的功能和机制还不完全清楚。我们发现 circ-ERBB2 在 GC 组织和细胞中显著增加。值得注意的是，肿瘤组织中 circ-ERBB2 的上调与患者的肿瘤大小、浸润深度和总生存率有关。一系列的增益和缺失功能实验表明，它在 GC 细胞中具有致癌作用，包括细胞增殖、凋亡、迁移和侵袭。我们进一步通过生物信息学分析和荧光素酶报告系统预测并鉴定了 circ-ERBB2 吸附 miR-503 和 miR-637。然后预测并证实 CACUL1 和 MMP-19 分别是 miR-503 和 miR-637 的靶基因。此外，挽救实验表明，circ-ERBB2 通过 miR-503/CACUL1 和 miR-637/MMP-19 通路分别促进肿瘤的生长和侵袭。总之，这些发现表明 circ-ERBB2 在 GC 中作为癌基因发挥作用，可能有助于开发针对这种致命恶性肿瘤的有前途的治疗方法。
