乳腺癌是一个异质性的疾病，三阴性乳腺癌是预后较差的分子亚型，化疗耐药和转移是影响预后的主要因素。近来研究表明肿瘤微环境影响着肿瘤的生物学行为，CAF作为肿瘤微环境的主要组成成分，能否通过外泌体传递circRNA调控三阴性乳腺癌转移及化疗耐药有待深入探讨。为了筛选三阴性乳腺癌CAF外泌体中有潜在功能的circRNA，我们构建了有无转移的三阴性乳腺癌CAF细胞系CAF-M和CAF-N，利用RNA-seq高通量测序筛选出3个circRNAs进行深入研究。从体外、体内实验和临床标本分析三个层面探讨候选circRNAs对三阴性乳腺癌化疗耐药和转移的影响，并明确其分子机制。本课题首次分析了CAF外泌体中circRNA的表达，从肿瘤微环境角度揭示CAF外泌体circRNA影响三阴性乳腺癌化疗耐药和转移的分子机制，为三阴性乳腺癌的预后提供重要的分子标志物，也将为靶向三阴性乳腺癌CAF的新型治疗奠定基础。

Breast cancer is a heterogeneous disease and triple negative breast cancer (TNBC) is characterized by unfavorable prognosis. Chemoresistance and metastasis are the main factors influencing prognosis in TNBC. Recent studies have revealed that tumor microenvironment plays important roles in the biological behaviors of tumor. Carcinoma-associated fibroblast (CAF) is an important component of tumor microenvironment. However, whether CAF could influence chemoresistance and metastasis in TNBC through exosome by delivering circular RNA (circRNA) remains unknown. To screen exosomal circRNAs modulating chemoresistance and metastasis in TNBC, we firstly established the CAF cell lines derived from TNBC primary tissue with or without metastasis (namely, CAF-M and CAF-N). With RNA-seq high-throughput sequencing analysis, three candidate circRNAs were identified for further study. We explored their roles in chemoresistance and metastasis both in vivo and in vitro and also in clinical breast cancer samples, and we further explored the underlying molecular mechanisms. This is the first study to investigate the circRNA expression in the exosome of CAF, illustrating their function and underlying mechanisms in chemoresistance and metastasis in TNBC. Our study may provide important markers for the prognostic evaluation of TNBC, and may also lay the foundation for the therapeutic strategy of targeting CAF in TNBC.