Upregulation of circular RNA circ-ERBB2 predicts unfavorable prognosis and facilitates the progression of gastric cancer via miR-503/CACUL1 and miR-637/MMP-19 signaling
Upregulation of circular RNA circ-ERBB2 predicts unfavorable prognosis and facilitates the progression of gastric cancer via miR-503/CACUL1 and miR-637/MMP-19 signaling
复制标题
DOI：
10.1016/j.bbrc.2019.03.010
复制
发表时间：
2019-04-16
影响因子：
3.1
通讯作者：
Cao, Ting
中科院分区：
文献类型：
--
作者：
Li, Xuesong;He, Mu;Cao, Ting
胃癌是消化道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，环状rna在胃癌（GC）中的功能和机制尚不完全清楚。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、侵袭深度和总生存期有关。一系列的功能增益和功能丧失实验表明其在胃癌细胞中的致癌作用，包括细胞增殖、凋亡、迁移和侵袭。我们通过生物信息学分析和荧光素酶报告系统进一步预测和鉴定了circ-ERBB2海绵miR-503和miR-637。然后预测并确认CACUL1和MMP-19分别为miR-503和miR-637的靶标。此外，挽救实验表明circ-ERBB2分别通过miR-503/CACUL1和miR-637/MMP-19途径促进肿瘤生长和侵袭。总之，这些发现表明circ-ERBB2在胃癌中起致癌基因的作用，可能有助于开发这种致命恶性肿瘤的有希望的治疗方法。(C) 2019 Elsevier Inc.版权所有。
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. (C) 2019 Elsevier Inc. All rights reserved.