乳腺癌（BC）是威胁全球女性健康的最常见的恶性肿瘤之一。据报道，环状RNA（circRNA）在调节肿瘤进展和肿瘤微环境（TME）重塑中发挥着重要作用。利用高通量测序和生物信息学分析验证了BC中circRNA的差异表达特征和免疫相关性。通过纳米粒子透射电子显微镜和跟踪分析来表征外泌体。 circ-0100519 在 BC 发育中的生物学功能已在体外和体内得到证实。通过蛋白质印迹、RNA pull-down、RNA 免疫沉淀、流式细胞术和荧光素酶报告基因来研究其潜在机制。Circ-0100519 在 BC 肿瘤组织中含量显着丰富，与不良预后相关。它可以被封装到分泌的外泌体中，从而通过诱导 M2 样巨噬细胞极化来促进 BC 细胞侵袭和转移。从机制上讲，circ-0100519 充当支架，增强去泛素化酶泛素特异性蛋白酶 7 (USP7) 与核之间的相互作用巨噬细胞中的类因子 2 (NRF2)，诱导 USP7 介导的 NRF2 去泛素化。此外，HIF-1α 可以作为上游效应子来增强 circ-0100519 转录。我们的研究表明，外泌体 circ-0100519 是 BC 诊断和预后的潜在生物标志物，而 HIF-1α 抑制剂 PX-478 可能提供治疗靶点BC.© 2024 作者。约翰·威利出版的《临床与转化医学》

Breast cancer (BC) is one of the most prevalent malignant tumours that threatens women health worldwide. It has been reported that circular RNAs (circRNAs) play an important role in regulating tumour progression and tumour microenvironment (TME) remodelling.Differentially expression characteristics and immune correlations of circRNAs in BC were verified using high-throughput sequencing and bioinformatic analysis. Exosomes were characterised by nanoparticle transmission electron microscopy and tracking analysis. The biological function of circ-0100519 in BC development was demonstrated both in vitro and in vivo. Western blotting, RNA pull-down, RNA immunoprecipitation, flow cytometry, and luciferase reporter were conducted to investigate the underlying mechanism.Circ-0100519 was significant abundant in BC tumour tissues and related to poor prognosis. It can be encapsulated into secreted exosomes, thereby promoting BC cell invasion and metastasis via inducing M2-like macrophages polarisation.Mechanistically, circ-0100519 acted as a scaffold to enhance the interaction between the deubiquitinating enzyme ubiquitin-specific protease 7 (USP7) and nuclear factor-like 2 (NRF2) in macrophages, inducing the USP7-mediated deubiquitination of NRF2. Additionally, HIF-1α could function as an upstream effector to enhance circ-0100519 transcription.Our study revealed that exosomal circ-0100519 is a potential biomarker for BC diagnosis and prognosis, and the HIF-1α inhibitor PX-478 may provide a therapeutic target for BC.© 2024 The Author(s). Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.