CircIRAK3 sponges miR-3607 to facilitate breast cancer metastasis
CircIRAK3 sponges miR-3607 to facilitate breast cancer metastasis
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CircIRAK3 海绵 miR-3607 促进乳腺癌转移
DOI：
10.1016/j.canlet.2018.05.033
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发表时间：
2018-01-01
期刊：
影响因子：
9.7
通讯作者：
Wang, Shouyu
中科院分区：
文献类型：
--
作者：
Wu, Jie;Jiang, Zerun;Wang, Shouyu
作为一类内源性非编码RNA，环状RNA(CircRNAs)最近被发现在多种恶性肿瘤中调节肿瘤的发生和发展。然而，CircRNAs在乳腺癌转移中的表达谱和功能在很大程度上是未知的。在这里，我们确定了一种新的CircRNA的表达，我们将其命名为CircIRAK3，它在转移性乳腺癌(BC)细胞中的表达增加，并预测BC的复发。BC细胞的功能获得和功能丧失研究表明，CircIRAK3促进了细胞在体内外的迁移、侵袭和转移，但不影响细胞增殖、克隆形成或细胞周期进展。利用CircIRAK3体内沉淀法和荧光素酶报告基因分析，我们鉴定miR-3607为CircIRAK3相关的miRNA。此外，RNA测序和生物信息学分析表明，miR-3607的靶基因叉头盒C_1(FOXC1)在CircIRAK3沉默的细胞中表达下调，并介导了CircIRAK3诱导的BC细胞迁移。有趣的是，FOXC1可以反过来与IRAK3启动子结合，触发一个正反馈循环，使IRAK3/miR-3607/FOXC1信号轴保持不变。综上所述，我们的研究结果表明，CircIRAK3可能在BC转移中发挥调节作用，并可能成为转移BC治疗的潜在靶点。
As a class of endogenous noncoding RNAs, circular RNAs (circRNAs) have been recently identified to regulate tumourigenesis and progression in multiple malignancies. However, the expression profiles and function of circRNAs in breast cancer metastasis are largely unknown. Here, we determined that the expression of a novel circRNA, which we named circIRAK3, was increased in metastatic breast cancer (BC) cells and predictive of BC recurrence. Gain-of-function and loss-of-function studies in BC cells demonstrated that circIRAK3 promoted cell migration, invasion and metastasis in vitro and in vivo but did not affect cell proliferation, colony formation or cell cycle progression. Using circIRAK3 in vivo precipitation and luciferase reporter assays, we identified miR-3607 as a circIRAK3-associated miRNA. Furthermore, RNA sequencing and bioinformatics analysis showed that forkhead box Cl (FOXC1), the target of miR-3607, was downregulated in circIRAK3-silenced cells and mediated circIRAK3-induced BC cell migration. Intriguingly, FOXC1 could, in turn, bind to the IRAK3 promoter, triggering a positive-feedback loop that perpetuated the circIRAK3/miR-3607/FOXC1 signaling axis. Collectively, our findings indicated that circIRAK3 may exert regulatory roles in BC metastasis and may be a potential target for metastatic BC therapy.