多发性骨髓瘤（MM）仍是不可治愈的疾病，最终会出现耐药导致治疗失败，其中自噬在耐药调节中发挥重要作用。我们的前期研究发现在TRPV2高表达MM患者及细胞中，其Ca2+/CaMKII及自噬相关基因的表达明显上升, 且对Bortezomib敏感性明显下降。遂我们推断TRPV2在MM耐药中发挥重要作用, 并提出研究目标：（1）阐明TRPV2诱导MM细胞自噬对Bortezomib耐药的生物学调节作用及机制；（2）提出针对TRPV2高表达MM细胞的新型靶向治疗。本项目拟采用病毒转染、ChIP-PCR、CO-IP及皮下成瘤等方法从基因、蛋白和体内外水平对此目标进行研究，揭示TRPV2在MM细胞中通过调节Ca2+/CaMKII/Beclin1促进细胞自噬的调控网络，证明该调控网络在促进MM细胞Bortezomib耐药中的作用，为从全新角度寻找MM治疗靶点及逆转耐药奠定理论基础。

Multiple myeloma (MM) remains incurable as most patients inevitably develop refractory disease on account of drug resistance, and autophagy plays a vital role in drug resistance. Recently, we identified that Ca2+/CaMKII and autophagy-related genes were up-regulated in TRPV2-overexpressed MM cells, and these cells were insensitive to Bortezomib. Therefore, we presume that TRPV2 may make important roles in the drug resistance of MM, and propose specific aims: (1) To examine the mechanistic link between TRPV2-induced autophagy and drug resistance. (2) To offer a novel TRPV2-targeted treatment of MM. To verify these aims, combined with lentivirus transfection, ChIP-PCR, CO-IP and subcutaneous xenotransplanted tumor model, we will investigate the mechanism at the genomic and proteomic level. This project intends to reveal the regulatory network of TRPV2 inducing drug resistance through Ca2+/CaMKII/Beclin1 signaling in MM, clarify specific mechanisms of TRPV2/Ca2+/CaMKII/Beclin1 signaling involved in Bortezomib resistance. Our project will identify novel treatment target, which will provide a theoretical basis for overcoming the drug resistance of MM.