Breast Disease Center, The Affiliated Hospital of Qingdao University, Qingdao, P.R. China.
Central Laboratory of Molecular Biology, The Affiliated Hospital of Qingdao University, Qingdao, P.R. China.
FASEB J. 2020 Sep;34(9):11405-11420. doi: 10.1096/fj.201903047R. Epub 2020 Jul 30.
Increasing evidence indicates that circular RNAs (circRNAs) play a crucial role in regulating microRNAs (miRs) and mRNAs during breast cancer (BC) progression. Based on the in silico analysis of circRNA/miR/mRNA in BC, we aim to define an important role of circRNA_000554 in BC in relation to miR-182 and zinc finger protein 36 (ZFP36). Low expression of circRNA_000554 and ZFP36, and high miR-182 expression were determined in the clinical BC tissues. CircRNA_000554 acted as a sponge of miR-182, and miR-182 directly targeted ZFP36. After that, in order to evaluate the effects of circRNA_000554, miR-182, and ZFP36 on cellular process, we evaluated in vitro epithelial-mesenchymal transition (EMT) and in vivo tumor growth after delivering a series of overexpression plasmids, mimic, inhibitor, or shRNAs into BC cells. Increasing circRNA_000554 suppressed EMT, cell invasion and migration during BC by depleting miR-182 and increasing ZFP36. The inhibitory effect of circRNA_000554 on tumor growth was validated in vivo. Taken together, the present study confirms that circRNA_000554 functioned as an inhibitor of EMT in BC and suggests a molecular mechanism that circRNA_000554 bound to miR-182 to upregulate ZFP36 in this process.
越来越多的证据表明，环状 RNA（circRNA）在乳腺癌（BC）进展过程中在调节 microRNA（miR）和 mRNA 方面发挥着关键作用。基于 BC 中 circRNA/miR/mRNA 的计算机分析，我们旨在确定 circRNA_000554 在与 miR-182 和锌指蛋白 36（ZFP36）相关的 BC 中的重要作用。在临床 BC 组织中确定 circRNA_000554 和 ZFP36 的表达水平较低，而 miR-182 的表达水平较高。circRNA_000554 充当 miR-182 的海绵，而 miR-182 直接靶向 ZFP36。之后，为了评估 circRNA_000554、miR-182 和 ZFP36 对细胞过程的影响，我们在将一系列过表达质粒、模拟物、抑制剂或 shRNA 导入 BC 细胞后，评估了体外上皮-间充质转化（EMT）和体内肿瘤生长。通过耗尽 miR-182 和增加 ZFP36，增加 circRNA_000554 抑制 BC 中的 EMT、细胞侵袭和迁移。circRNA_000554 对肿瘤生长的抑制作用在体内得到了验证。总之，本研究证实 circRNA_000554 在 BC 中作为 EMT 的抑制剂发挥作用，并提出了一个分子机制，即 circRNA_000554 与 miR-182 结合，在此过程中上调 ZFP36。
