Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, People's Republic of China.
Cancer Biol Ther. 2023 Dec 31;24(1):2246205. doi: 10.1080/15384047.2023.2246205.
CircRNAs have been proven to play a pivotal role in cancer progression. The present study aims to explore the roles and related mechanisms of circSETD2 in breast cancer proliferation, migration and invasion. The expression of circSETD2 in BC was assessed by the GEO database and qRT‒PCR. The biological function and underlying molecular mechanism of circSETD2 in BC were explored using in vitro and in vivo experiments, including CCK8, transwell, RIP, western blot, and xenograft mouse models. The expression of circSETD2 was downregulated in BC tumors, in accordance with the GEO database. Overexpression of circSETD2 significantly suppressed cell growth, cell migration and invasion. Mechanistically, circSETD2 reduced the stabilization of YAP1 by competitively binding with HuR, resulting in inactivation of downstream targets such as CTGF, myc and Slug. Our work suggests that the novel signaling axis circSETD2/HuR/YAP1 plays an important role in BC progression. The molecular mechanism underlying this signaling axis may provide a potential therapeutic target for BC treatment.
CircRNAs 已被证明在癌症进展中发挥关键作用。本研究旨在探讨 circSETD2 在乳腺癌增殖、迁移和侵袭中的作用及相关机制。通过 GEO 数据库和 qRT-PCR 评估 circSETD2 在 BC 中的表达。通过体外和体内实验（包括 CCK8、transwell、RIP、western blot 和异种移植小鼠模型）探索 circSETD2 在 BC 中的生物学功能和潜在分子机制。circSETD2 在 BC 肿瘤中的表达下调，与 GEO 数据库一致。circSETD2 的过表达显著抑制细胞生长、细胞迁移和侵袭。机制上，circSETD2 通过与 HuR 竞争结合来减少 YAP1 的稳定性，从而使下游靶标如 CTGF、myc 和 Slug 失活。我们的工作表明，新型信号轴 circSETD2/HuR/YAP1 在 BC 进展中发挥重要作用。该信号轴的分子机制可能为 BC 治疗提供潜在的治疗靶点。
