亲环蛋白A（CypA）是一种参与多种癌症事件的肽基脯氨酰异构酶，但从未考虑过CypA在卵巢癌（OC）中异常表达和调节的分子机制。这项研究确定 CypA 是卵巢癌上皮间质转化 (EMT) 的关键驱动因素，并探讨了这一过程的机制。我们发现 CypA 在卵巢癌患者的组织和血清中表达上调，并且 CypA 过度表达与不良预后相关。 CypA 在皮下肿瘤异种移植和腹部转移模型中促进体内肿瘤生长和转移，体外研究提示了一种机制，表明 CypA 通过激活 PI3K/AKT 信号通路加速卵巢癌细胞上皮间质转化。机制研究表明，STAT5A结合pri-miR-514a-3p并抑制其活性，而miR-514a-3p直接结合CypA的3'-UTR抑制其表达，导致STAT5A促进CypA的表达，形成STAT5A/miR-514a-3p/CypA 轴。此外，免疫沉淀和质谱分析确定了 CypA 与 TAF15 的相互作用，通过抑制其蛋白酶体降解来稳定 TAF15，并促进其进入细胞核。而STAT5A则受到TAF15的正向调节。我们的研究结果确定了 CypA 的一个新的反馈环路，它通过卵巢癌中的 TAF15/STAT5A/miR-514a-3p 通路驱动 EMT 和卵巢肿瘤的生长和转移，并促进 CypA 释放到细胞外，这为卵巢癌提供了一个有希望的治疗靶点。 OC 治疗和诊断生物标志物。© 2024。作者，获得 Springer Nature Limited 的独家许可。

Cyclophilin A (CypA) is a peptidyl-prolyl isomerase that participates in multiple cancer events, but the molecular mechanisms of abnormal expression and regulation of CypA in ovarian cancer (OC) have never been considered. This study identifies CypA as a key driver of epithelial-mesenchymal transition (EMT) in ovarian cancer and explores the mechanisms that underly this process. We show that CypA is upregulated in tissues and serum of ovarian cancer patients and that CypA overexpression correlates with poor prognosis. CypA facilitates tumor growth and metastasis in vivo in subcutaneous tumor xenograft and abdominal metastatic models, and in vitro studies suggest a mechanism, showing that CypA accelerates ovarian cancer cell epithelial-mesenchymal transition by activating a PI3K/AKT signaling pathway. Mechanistic studies showed that STAT5A binds pri-miR-514a-3p and inhibits its activity, whereas miR-514a-3p directly binds to the 3'-UTR of CypA to suppress its expression, resulting in STAT5A promoting the expression of CypA, forming the STAT5A/miR-514a-3p/CypA axis. Furthermore, immunoprecipitates and mass spectrometry analysis identifies a CypA interaction with TAF15 that stabilizes TAF15 by suppressing its proteasome degradation and promotes its entry into the nucleus. While STAT5A is positively regulated by TAF15. Our findings identify a novel feedback loop for CypA that drives EMT and ovarian tumor growth and metastasis via a TAF15/STAT5A/miR-514a-3p pathway in ovarian cancer and facilitates the release of CypA into the extracellular, which provides a promising therapeutic target for OC treatment and a diagnostic biomarker.© 2024. The Author(s), under exclusive licence to Springer Nature Limited.