三阴性乳腺癌化疗耐药和进展转移编码环状RNA的筛选及功能研究

乳腺癌是严重威害女性生命健康的恶性肿瘤，其中三阴性乳腺癌是一种恶性程度高、预后差的分子亚型。化疗耐药和转移是影响三阴性乳腺癌预后的主要因素。最近发现部分环状RNA（circRNA）具有蛋白编码功能，但其功能尚知之甚少。本项目拟从编码circRNA的崭新视角研究三阴性乳腺癌化疗耐药及进展转移的分子机理。我们构建三阴性乳腺癌化疗耐药细胞系和肺高转移能细胞系，并结合临床样本，通过核糖体circRNA高通量测序技术筛选出3个与三阴性乳腺癌化疗耐药与转移相关的具有编码潜能的circRNA进行深入研究。我们通过体外、体内实验及临床样本分析等多层面验证候选编码circRNA的功能，探讨其对三阴性乳腺癌化疗耐药和转移的调控作用及分子机制，并明确其临床应用价值。本课题的完成将有助于揭示编码circRNA在三阴性乳腺癌耐药转移过程中的重要作用，将为三阴性乳腺癌的耐药预测及预后分析提供重要的新型分子标记物。

Breast cancer is a malignant tumor which seriously threatens the life and health of women. Triple negative breast cancer (TNBC) is a special molecular subtype characterized with high malignancy and unfavorable prognosis. Chemoresistance and metastasis are the main factors influencing prognosis in TNBC. Recently, some circular RNA (circRNA) have been found to have protein-coding function, however, the functions of coding circRNA are still poorly understood. Our current project is to explore the role of coding circRNA in chemoresistance and metastasis for TNBC. We firstly established a chemoresistant TNBC cell line and a highly lung-metastatic TNBC cell line. Combining with clinical samples after chemotherapy, three candidate coding circRNA were identified for further study by ribosomal circRNA high-throughput sequencing analysis. We verified the functions of candidate coding circRNA in chemoresistance and metastasis both in vivo and in vitro and also in clinical breast cancer samples. We further explored the underlying molecular mechanisms and clarified their clinical value. The completion of this study will help to reveal the important role of coding circRNA in chemoresistance and metastasis, and provide novel molecular markers for drug-resistant prediction and prognostic evaluation in TNBC.