B细胞通过细胞外囊泡分泌长链非编码RNA LINC00926抑制乳腺癌转移的临床及机制研究

复发转移是乳腺癌死亡的主要原因。B细胞在影响肿瘤进展及疗效中的作用日益凸显。细胞外囊泡（Extracellular Vesicle，EVs）可参与细胞间信号传递，调控肿瘤进展，lncRNA作为信使发挥重要作用。课题组前期发现LINC00926在B细胞中优势表达，乳腺癌细胞与B细胞或其EVs共培养及EVs染色实验，发现LINC00926可以EVs为介质进入肿瘤细胞。高表达LINC00926可明显抑制细胞侵袭和迁移；稳转株RNA测序结合GSEA分析发现LINC00926显著抑制EMT相关基因，提示LINC00926可能通过影响EMT抑制乳腺癌转移。本课题拟利用临床样本明确乳腺癌组织微环境中LINC00926表达、定位与预后的关系，体内外实验及乳腺癌类器官模型阐明微环境中B细胞借助LINC00926为信使影响EMT抑制乳腺癌侵袭转移的分子机制，为乳腺癌转移及预后提供新的干预靶点及活检指标。

Breast cancer is the most malignant tumor in women. Recurrence and metastasis are the leading causes of breast cancer death. Recent years, more and more studies have focused on the role of B-lymphocytes in tumor progression and therapeutic effect. LncRNAs which can be transported by extracellular vesicles (EVs) mainly serve as messengers in the communication in tumor microenvironment. We have identified a LncRNA LINC00926 which was mainly expressed in B-lymphocytes in our study. After co-culture of B-lymphocytes or EVs derived from B cells and breast cancer cells, LINC00926 was significantly up-regulated in breast cancer cells, suggesting that LINC00926 might be derived from B-cells and extracellular vesicle-packaged LINC00926 could enter into tumor cells. Function studies revealed that LINC00926 could significantly inhibit the migration and invasion of tumor cells. RIP and Mass Spectrometry analysis revealed that LINC00926 interacted with HNRNPC, which was a RNA/DNA binding protein. RNA-seq analysis furhter revealed that knock-down of LINC00926 significantly inhibited EMT pathways, suggesting that LINC00926 might inhibit the metastasis of tumor cells by affecting EMT signaling. All these data suggest that extracellular vesicle-packaged LINC00926 from B lymphocytes might inhibit breast cancer metastasis through regulation of EMT pathway..However, the detailed mechanism remains unknown. Our further research is to verify the prognostic value of LINC00926 and B cells in tumor tissue with independent clinical samples and investigate the role and the precise mechanism of LINC00926 in breast cancer metastasis with cell lines, animal xenografts, and patient-derived organoid models. Taken together, our study will highlight the potential of LINC00926 as signal transducers that are transmitted frome B cells to tumour cells via EVs to promote cancer metastasis and provide new insights into the prediction value of LINC00926.