多发性骨髓瘤耐药miRNA 标志物的筛选及机制研究

多发性骨髓瘤（MM）是浆细胞恶性增生肿瘤，发病机制复杂，普遍耐药导致生存率低是该病的特点。因此，确认耐药诊断和预后判断的标志物很重要。根据该病耐药基因调节网络和miRNA的特点，筛选耐药miRNA是理论可行且最适该病预后判断标志物获得的窗口。本研究拟选择用药前后MM患者骨髓及血清样本，通过miRNA芯片筛选、耐药靶基因调节分析、荧光定量PCR验证来进行耐药及预后诊断miRNA标志物的筛选和最终确认，并研究其与MM不同发病类型的关系，为MM临床治疗提供明确的耐药诊断标志物。另外，在前期研究备选标志物中，miR-202是我们新证明的可调节B细胞活化因子的miRNA，其在MM耐药的机制有待本研究阐明。在最终标志物的公共性确认中，我们也将对miR-202进行认证。本课题的开展将获得一些明确的miRNA作为MM耐药及预后判断的标志物；同时可探明MM新的耐药调节机制，为新药开发提供靶点。

Multiple myeloma (MM) is the tumor characterized by malignant proliferation of plasma cells with complex pathogenesis and widespread drug resistance resulting in low survival rate. It is very important to find diagnostic and prognostic markers. MM drug-resistant miRNA screening is practical in theory and most suitable for obtaining the prognostic markers based on miRNA characteristics and the drug-resistant gene regulatory networks of MM. We are planning to screen and finally confirm the drug-resistant and prognostic miRNA markers by miRNA microarray screening, drug-resistant target gene regulation analysis, real-time PCR with patients' bone marrow and serum samples before and after the cure, combined with the study of the relationship between MM different types and these markers to provide clear drug-resistant diagnostic markers for the clinical treatment of MM. In addition, among the selected markers of our preliminary studies, miR-202, which is newly proved to be the miRNA that can regulate B-cell activating factor, needs our study to clarify its role in MM drug-resistant mechanism. We will also confirm the role of miR-202 in the final common markers. This study will obtain some clear miRNAs as MM drug-resistant and prognostic biomarkers, at the same time, we can also clarify some new MM drug-resistant regulation mechanisms to provide targets for novel drug development.