Circ-PTK2调控miR-638/Wnt&ERK通路对多发性骨髓瘤耐药机制的相关研究

耐药是多发性骨髓瘤（MM）复发难治的主要原因，也是临床治疗的难题，但耐药机制及如何逆转耐药研究尚少。近来研究发现circ RNA在调控MM细胞发生、发展机制，及不良预后密切相关。我们前期工作发现，circ PTK2在MM患者中高表达，导致不良预后，且PTK2可通过调控miR-638/Wnt&ERK通路调节MM细胞的临床特征；PTK2在耐药MM细胞中表达量更高，并调控耐药MM细胞活性。据此，我们推测：PTK2可通过调控miR-638/Wnt&ERK通路参与MM耐药。本课题拟在前期工作基础上进一步阐明：Circ PTK2通路与MM耐药发生的关系； PTK2调控耐药MM细胞的恶性表型、在小鼠中的成瘤及其具体分子机制；沉默PTK2通路对于耐药MM细胞的杀伤作用和耐药MM模型小鼠的治疗作用。本项目的实施将为逆转MM耐药机制提供理论依据，为临床逆转耐药治疗提供全新思路。

Drug-resistant cells are one of the essential causes of reduced survival rate and relapse in multiple myeloma (MM), and few studies have reported that CircRNA regulates the biological function of drug-resistant MM cells. Our previous study found that high expression of Circ PTK2 in MM patients was associated with poor prognosis and poor response to the treatment. PTK2 can regulate the malignant phenotype of MM cells by regulating the miR-638/Wnt&ERK pathway. PTK2 is highly expressed in drug-resistant MM cells and regulates the activity of drug-resistant MM cells.Therefore, we propose the key scientific hypothesis that PTK2 can regulate the malignant phenotype of drug-resistant MM cells by regulating the miR-638/Wnt&ERK pathway. This project will solve the following problems on the basis of previous studies: 1. PTK2 regulates the malignant phenotype of drug-resistant MM cells, tumorigenesis in mice and its potential molecular mechanism; 2. Killing effect of silencing PTK2/miR-638/Wnt&ERK pathway on drug-resistant MM cells and therapeutic effect on drug-resistant MM model mice. The implementation of this progrom will provide theoretical support for treatment of drug resistance MM with targeting PTK2, and provide a new idea for the clinical treatment of drug resistance MM.