CircEIF3H-IGF2BP2-HuR scaffold complex promotes TNBC progression via stabilizing HSPD1/RBM8A/G3BP1 mRNA.
CircEIF3H-IGF2BP2-HuR scaffold complex promotes TNBC progression via stabilizing HSPD1/RBM8A/G3BP1 mRNA.
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CircEIF3H-IGF2BP2-HuR支架复合物通过稳定HSPD1/RBM8A/G3BP1 mRNA促进TNBC进展
DOI：
10.1038/s41420-022-01055-9
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发表时间：
2022-05-14
影响因子：
7
通讯作者：
Yang, Qifeng
中科院分区：
文献类型：
--
作者：
Song, Xiaojin;Chen, Bing;Liang, Yiran;Li, Yaming;Zhang, Hanwen;Han, Dianwen;Wang, Yajie;Ye, Fangzhou;Wang, Lijuan;Zhao, Wenjing;Yang, Qifeng
三阴性乳腺癌是一种预后不良的分子亚型，转移是临床治疗失败的主要原因。然而，circRNA在TNBC进展中的表达谱和调控功能尚未完全了解。在本文中，我们在配对的乳腺癌组织和邻近的正常组织中进行了高通量RNA-seq，并发现了一种新的circRNA，circEIF 3 H，它在乳腺癌组织中上调。大型队列生存分析证实了circEIF 3 H高表达与TNBC预后不良之间的相关性，表明circEIF 3 H在TNBC进展中的重要功能。然后，我们进行了体外和体内实验，这表明circEIF 3 H是TNBC增殖和转移所必需的。进一步的实验表明，circEIF 3 H不像大多数成熟的途径那样作为microRNA海绵，而是作为IGF 2BP 2和HuR的支架来调节HSPD 1，RBM 8A和G3 BP 1的mRNA稳定性。我们的研究结果提供了一种新的circRNA，circEIF 3 H，通过作为IGF 2BP 2/HuR的支架具有显着的促癌功能。这些结果将circEIF 3 H确定为在不久的将来开发TNBC个体化治疗的潜在靶标。
Triple-negative breast cancer (TNBC) is a molecular subtype with an unfavorable prognosis, and metastasis is the main reason for the failure of clinical treatment. However, the expression profile and regulatory function of circRNAs in TNBC progression are not fully understood. Herein, we performed high-throughput RNA-seq in paired breast cancer tissues and adjacent normal tissues and discovered a novel circRNA, circEIF3H, which was upregulated in breast cancer tissues. Large cohort survival analysis confirmed the association between high circEIF3H expression and poor prognosis of TNBC, indicating the vital function of circEIF3H in TNBC progression. Then we conducted both in vitro and in vivo experiments which illustrated that circEIF3H was essential for TNBC proliferation and metastasis. Further experiments showed that circEIF3H did not function as a microRNA sponge as in the most well-established pathway, but as a scaffold for IGF2BP2 and HuR to regulate the mRNA stability of HSPD1, RBM8A, and G3BP1. Our findings provide insight into a novel circRNA, circEIF3H, with significant cancer-promoting function via serving as a scaffold for IGF2BP2/HuR. These results identified circEIF3H as a potential target for developing individualized therapy of TNBC in the approaching future.
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影响因子：
37.3
作者：
Zeng K;He B;Yang BB;Xu T;Chen X;Xu M;Liu X;Sun H;Pan Y;Wang S
通讯作者：
Wang S
影响因子：
37.3
作者：
Winslow S;Leandersson K;Larsson C
通讯作者：
Larsson C
影响因子：
7.7
作者：
Dai, Ning;Ji, Fei;Avruch, Joseph
通讯作者：
Avruch, Joseph
影响因子：
11.2
作者：
Heinonen, M;Bono, P;Ristimäki, A
通讯作者：
Ristimäki, A
影响因子：
8
作者：
Mazan-Mamczarz, K.;Hagner, P. R.;Corl, S.;Srikantan, S.;Wood, W. H.;Becker, K. G.;Gorospe, M.;Keene, J. D.;Levenson, A. S.;Gartenhaus, R. B.
通讯作者：
Gartenhaus, R. B.