多发性骨髓瘤外泌体中miR-21/146a通过Notch及NF-κB 信号通路调控MSCs转化的机制研究

多发性骨髓瘤（MM）的外泌体可通过其内的microRNAs（miRs）介导恶性骨髓微环境细胞之间的相互作用，从而促进MM增殖及耐药。我们前期研究发现MM外泌体中miR-21及miR-146a可促进间充质干细胞（MSCs）的增殖、向肿瘤相关成纤维细胞（CAFs）转化及分泌IL-6，但具体调控机制不明确。本课题拟在前期研究基础上，进行如下研究：1）全面分析MM外泌体中miR-21及miR-146a与临床特征的相关性，判断其预后意义；2）结合体内外实验深入研究MM外泌体中miR-21及miR-146a介导的MSCs向CAFs转化，并参与MM细胞增殖及耐药的功能；3）阐明MM外泌体中miR-21及miR-146a通过PI3K/Akt/NF-κB及Notch信号通路调控MSCs向CAFs转化的具体分子机制，为MM的治疗提供新思路。

Exosomes, through delivering biological molecules such as microRNAs (miRs), represent a novel component of malignant bone marrow microenvironment and play an important role in the proliferation and drug resistance of MM. Our previous study has been shown that the exosomal miR-21 and miR-146a derived from multiple myeloma (MM) cells could regulate the proliferation, cancer-associated fibroblast (CAF) transition and IL-6 secretion of mesenchymal stem cells (MSCs). Based on our previous results, we intend to carry out the following experiments: 1) analyze the roles of exosomal miR-21 and miR-146a in predicting the prognosis of MM; 2) explore the pathological role of MSCs transition in the proliferation and drug resistance of MM; 3) investigate the molecular mechanisms of exosomal miR-21 and miR-146a in the transition of MSCs via regulating the PI3K/Akt/NF-κB and Notch signaling pathways. This project will be helpful to provide new insights in MM treatment.