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.

中文翻译：

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环状RNA 000554通过调节microRNA-182/ZFP36轴抑制乳腺癌上皮间质转化

越来越多的证据表明，环状 RNA (circRNA) 在乳腺癌 (BC) 进展过程中在调节微小 RNA (miR) 和 mRNA 方面发挥着至关重要的作用。基于对 BC 中 circRNA/miR/mRNA 的计算机分析，我们旨在确定 circRNA_000554 在 BC 中与 miR-182 和锌指蛋白 36（ZFP36）相关的重要作用。在临床 BC 组织中确定了 circRNA_000554 和 ZFP36 的低表达和 miR-182 的高表达。CircRNA_000554 作为 miR-182 的海绵，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，我们在递送一系列过表达质粒、模拟物、抑制剂、或 shRNA 进入 BC 细胞。增加circRNA_000554通过消耗miR-182和增加ZFP36来抑制BC期间的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验证。总之，本研究证实了 circRNA_000554 在 BC 中起到了 EMT 抑制剂的作用，并提出了 circRNA_000554 与 miR-182 结合以在此过程中上调 ZFP36 的分子机制。