Circular RNA 0047905 acts as a sponge for microRNA4516 and microRNA1227-5p, initiating gastric cancer progression

Circular RNA 0047905 acts as a sponge for microRNA4516 and microRNA1227-5p, initiating gastric cancer progression
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环状RNA 0047905充当microRNA4516和microRNA1227-5p的海绵,启动胃癌进展

DOI:
10.1080/15384101.2019.1618122
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发表时间:
2019-01-01
期刊:
影响因子:
4.3
通讯作者:
Jiang, Kewei
Jiang, Kewei
中科院分区:
生物学3区
文献类型:
--
作者:
Lai, Zhiyong;Yang, Yang;Jiang, Kewei

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摘要许多证据表明,环状RNA在肿瘤的发生和发展中起着重要作用。然而,我们对circRNA在胃癌(GC)中的作用的认识仍然有限。我们通过使用miRNA微阵列分析胃癌组织和配对的非癌粘膜组织中的miRNA表达,研究了环状RNA 0047905(circRNA 0047905)在胃癌发病机制中可能作为肿瘤促进剂的可能性。接下来,根据结合circRNA和mRNA的常见miRNA构建ceRNA网络。从机制上讲,我们证明了circRNA 0047905直接结合miR 4516和miR 1227 - 5 p,缓解了对靶标SERPINB 5和MMP 11的抑制。我们观察到,下调胃癌细胞中的circRNA 0047905表达抑制Akt/CREB信号通路的激活。RNA原位杂交显示circRNA 0047905在胃癌中有表达。我们的数据表明,circRNA 0047905是GC诊断和治疗的一个有希望的靶点。
ABSTRACT Several lines of evidence suggest that circular RNAs (circRNAs) play important roles in oncogenesis and tumor progression. However, our knowledge of the role of circRNAs in gastric cancer (GC) remains limited. We investigated the possibility that circular RNA 0047905 (circRNA0047905) might act as a tumor promoter in the pathogenesis of gastric cancer by profiling miRNA expression in GC tissues and paired noncancerous mucosa tissues using miRNA microarrays. Next, a ceRNA network was constructed according to common miRNAs binding circRNAs and mRNAs. Mechanistically, we demonstrated that circRNA0047905 directly binds miR4516 and miR1227-5p, relieving suppression for targets SERPINB5 and MMP11. We observed that down-regulated circRNA0047905 expression in gastric cancer cells inhibited Akt/CREB signaling pathway activation. RNA scope in situ hybridization revealed expression of circRNA0047905 in GC. Our data suggest that circRNA0047905 is a promising target for GC diagnosis and therapy.