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环状 RNA 0047905 作为 microRNA4516 和 microRNA1227-5p 的海绵体,引发胃癌进展。

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

机构信息

a Department of General Surgery , Shanxi Dayi Hospital, Shanxi Academy of Medical Sciences , Taiyuan , Shanxi , People's Republic of China.

b Department of Breast Center , Peking University People's Hospital , Beijing , People's Republic of China.

出版信息

Cell Cycle. 2019 Jul;18(14):1560-1572. doi: 10.1080/15384101.2019.1618122. Epub 2019 Jun 4.

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.

摘要

有几条线索表明,环状 RNA(circRNA)在肿瘤发生和肿瘤进展中发挥重要作用。然而,我们对 circRNA 在胃癌(GC)中的作用的了解仍然有限。我们通过 miRNA 微阵列分析 GC 组织和配对的非癌性黏膜组织中的 miRNA 表达,研究了环状 RNA 0047905(circRNA0047905)是否可能通过促进胃癌的发病机制发挥肿瘤促进剂的作用。接下来,根据常见的 miRNA 结合 circRNA 和 mRNAs 构建了 ceRNA 网络。从机制上讲,我们证明 circRNA0047905 可直接结合 miR4516 和 miR1227-5p,从而解除对靶标 SERPINB5 和 MMP11 的抑制。我们观察到下调胃癌细胞中的 circRNA0047905 表达可抑制 Akt/CREB 信号通路的激活。RNAscope 原位杂交显示 circRNA0047905 在 GC 中的表达。我们的数据表明,circRNA0047905 是 GC 诊断和治疗的有前途的靶标。

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