Song Xiaojin, Chen Bing, Liang Yiran, Li Yaming, Zhang Hanwen, Han Dianwen, Wang Yajie, Ye Fangzhou, Wang Lijuan, Zhao Wenjing, Yang Qifeng
Department of Breast Surgery, Qilu Hospital of Shandong University, Jinan, Shandong Province, 250012, China.
Pathology Tissue Bank, Qilu Hospital of Shandong University, Jinan, Shandong Province, 250012, China.
Cell Death Discov. 2022 May 14;8(1):261. doi: 10.1038/s41420-022-01055-9.
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.
三阴性乳腺癌（TNBC）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明确。在此，我们对配对的乳腺癌组织和相邻正常组织进行了高通量RNA测序，发现了一种新的circRNA，即circEIF3H，其在乳腺癌组织中上调。大样本队列生存分析证实了circEIF3H高表达与TNBC预后不良之间的关联，表明circEIF3H在TNBC进展中具有重要作用。随后我们进行了体外和体内实验，结果表明circEIF3H对TNBC的增殖和转移至关重要。进一步实验表明，circEIF3H并不像最经典的途径那样作为微小RNA海绵发挥作用，而是作为IGF2BP2和HuR的支架来调节HSPD1、RBM8A和G3BP1的mRNA稳定性。我们的研究结果揭示了一种新的circRNA，即circEIF3H，它通过作为IGF2BP2/HuR的支架具有显著的促癌功能。这些结果确定circEIF3H是在不久的将来开发TNBC个体化治疗的潜在靶点。
