The pro-metastasis effect of circANKS1B in breast cancer.
The pro-metastasis effect of circANKS1B in breast cancer.
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DOI：
10.1186/s12943-018-0914-x
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发表时间：
2018-11-19
期刊：
影响因子：
37.3
通讯作者：
Wang S
中科院分区：
文献类型：
--
作者：
Zeng K;He B;Yang BB;Xu T;Chen X;Xu M;Liu X;Sun H;Pan Y;Wang S
最近的研究表明，环状RNA （circRNA）在癌症进展中起着关键作用。在这里，我们试图研究它在乳腺癌中的作用。CircANKS1B（源自ANKS1B基因外显子5 ~ 8的circRNA， hsa_circ_0007294）通过rna测序鉴定，并通过qRT-PCR和Sanger测序进行验证。使用临床乳腺癌样本来评估circANKS1B的表达及其与临床病理特征和预后的关系。在细胞系和小鼠异种移植模型中进行了功能获得和功能丧失实验，以支持临床发现，并阐明了circANKS1B在乳腺癌中的功能和潜在机制。与非TNBC组织和细胞系相比，CircANKS1B在三阴性乳腺癌（TNBC）中显著上调。circANKS1B表达升高与淋巴结转移和临床分期密切相关，是影响乳腺癌患者总生存的独立危险因素。功能研究显示，circANKS1B在体外和体内均通过诱导上皮-间质转化（epithelial-to-mesenchymal transition， EMT）促进乳腺癌的侵袭和转移，而对乳腺癌的生长没有影响。机制上，circANKS1B大量海绵miR-148a-3p和miR-152-3p增加转录因子USF1的表达，USF1可通过转录上调TGF-β1的表达，激活TGF-β1/Smad信号通路促进EMT。此外，我们发现circANKS1B在乳腺癌中的生物发生受到剪接因子ESRP1的促进，其表达也受到USF1的调节。我们的数据揭示了新型环状RNA circANKS1B在乳腺癌转移中的重要作用，这表明circANKS1B的治疗靶向可能更好地预防乳腺癌转移。本文的在线版本（10.1186/s12943-018-0914-x）包含补充材料，可供授权用户使用。
Recent studies indicate that circular RNA (circRNA) plays a pivotal role in cancer progression. Here, we sought to investigate its role in breast cancer. CircANKS1B (a circRNA originated from exons 5 to 8 of the ANKS1B gene, hsa_circ_0007294) was identified by RNA-sequencing and validated by qRT-PCR and Sanger sequencing. Clinical breast cancer samples were used to evaluate the expression of circANKS1B and its associations with clinicopathological features and prognosis. Gain- and loss-of-function experiments in cell lines and mouse xenograft models were performed to support clinical findings and elucidate the function and underlying mechanisms of circANKS1B in breast cancer. CircANKS1B was significantly up-regulated in triple-negative breast cancer (TNBC) compared with non-TNBC tissues and cell lines. Increased circANKS1B expression was closely associated with lymph node metastasis and advanced clinical stage and served as an independent risk factor for overall survival of breast cancer patients. Functional studies revealed that circANKS1B promoted breast cancer invasion and metastasis both in vitro and in vivo by inducing epithelial-to-mesenchymal transition (EMT), while had no effect on breast cancer growth. Mechanistically, circANKS1B abundantly sponged miR-148a-3p and miR-152-3p to increase the expression of transcription factor USF1, which could transcriptionally up-regulate TGF-β1 expression, resulting in activating TGF-β1/Smad signaling to promote EMT. Moreover, we found that circANKS1B biogenesis in breast cancer was promoted by splicing factor ESRP1, whose expression was also regulated by USF1. Our data uncover an essential role of the novel circular RNA circANKS1B in the metastasis of breast cancer, which demonstrate that therapeutic targeting of circANKS1B may better prevent breast cancer metastasis. The online version of this article (10.1186/s12943-018-0914-x) contains supplementary material, which is available to authorized users.
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影响因子：
28.5
作者：
Dong Y;He D;Peng Z;Peng W;Shi W;Wang J;Li B;Zhang C;Duan C
通讯作者：
Duan C
影响因子：
5.3
作者：
Dittmar, Kimberly A.;Jiang, Peng;Carstens, Russell P.
通讯作者：
Carstens, Russell P.
影响因子：
13.5
作者：
Han, Dan;Li, Jiangxue;Cao, Xuetao
通讯作者：
Cao, Xuetao
影响因子：
16
作者：
Rybak-Wolf, Agnieszka;Stottmeister, Christin;Rajewsky, Nikolaus
通讯作者：
Rajewsky, Nikolaus
影响因子：
64.5
作者：
Lambert AW;Pattabiraman DR;Weinberg RA
通讯作者：
Weinberg RA