乳腺癌（BC）是女性最常见的诊断为癌症和导致癌症相关死亡的主要原因。转移占BC相关死亡的大多数。解决这个具有挑战性的问题的一个可行策略是破坏肿瘤转移所需的能力。在这里，我们验证了一种新的BC转移抑制循环RNA，circPOKE。circPOKE在原发和转移性BC组织中表达下调，过表达circPOKE在体外和体内抑制了BC细胞的转移潜力，但不影响其增殖能力。在机制上，circPOKE竞争性结合到USP10，并减少其与Snail的结合，Snail是EMT的关键转录调控因子，从而通过蛋白质泛素化降解途径抑制Snail的稳定性。此外，我们发现circPOKE可通过外泌体分泌到细胞外空间，并且携带circPOKE的外泌体在体外和体内显著抑制了BC细胞的侵袭能力。此外，circPOKE、USP10和Snail的水平在BC中具有临床相关性，表明circPOKE可能作为BC转移患者的潜在治疗靶点。 © 2023. 作者与斯普林格自然有限公司签订的独家许可协议。

Breast cancer (BC) is the most commonly diagnosed cancer and the leading cause of cancer-related death among females. Metastasis accounts for the majority of BC related deaths. One feasible strategy to solve this challenging problem is to disrupt the capabilities required for tumor metastasis. Herein, we verified a novel metastasis suppressive circRNA, circPOKE in BC. circPOKE was downregulated in primary and metastatic BC tissues and overexpression of circPOKE inhibited the metastatic potential but not the proliferative ability of BC cells in vitro and in vivo. Mechanistically, circPOKE competitively binds to USP10, and reduces its binding to Snail, a key transcriptional regulator of EMT, thereby inhibiting Snail stability via the protein-ubiquitination degradation pathway. In addition, we found that circPOKE could be secreted into the extracellular space via exosomes and that exosome-carried circPOKE significantly inhibited the invasive capabilities of BC cells in vitro and in vivo. Furthermore, the levels of circPOKE, USP10 and Snail are clinically relevant in BC, suggesting that circPOKE may be used as a potential therapeutic target for patients with BC metastasis.© 2023. The Author(s), under exclusive licence to Springer Nature Limited.