MYC基因异常表达约占弥漫大B细胞淋巴瘤（DLBCL）的20%，是DLBCL难治、复发的主要原因，所以MYC信号途径是治疗DLBCL的重要靶点。miR-34a和let7在DLBCL中低表达，可调控MYC基因，且MYC和miR-34a交互作用形成恶性循环，加重DLBCL的不良预后，因此如何提高这两种microRNA在DLBCL细胞的表达，是治疗MYC基因异常表达DLCBL的新方法。我们前期掌握了构建双基因嵌合型溶瘤腺病毒的技术；也构建了携带miR-34a的痘溶瘤腺病毒，并可以在多种血液肿瘤细胞高效表达miR-34。本项目拟开展下列研究：构建携带miR-34a和let-7的双基因嵌合型溶瘤腺病毒，研究其双靶向阻断-34a与MYC的交互作用，从而抑制MYC基因的异常表达；进一步阐明其分子机制。本研究结合microRNA替代治疗和溶瘤病毒治疗，以期在治疗MYC异常表达的DLBCL研究领域中获得创新

The abnormal expression of MYC gene about 20% in Diffuse large B cell lymphoma (DLBCL) and it’s the main reason for refractory, recurrent. MYC and Bcl-2 signal pathway is a potential therapeutic target in DLBCL. It is reported that both miR-34a and let7 are low-expression in DLBCL and have the function to regulate MYC and cross-talk with MYC and miR-34a signal pathway, which would enhance MYC deregulation further. Therefore, restoration of these two miRNAs in DLBCL is a novel therapeutic strategy. Our previous studies have mastered the construction of chimeric oncolytic adenovirus technology，and demonstrated that oncolytic virus worked as an ideal transgene delivery system to restore miR-34a. This study is designed to carry out as following that: constructing a novel oncolytic adenovirus armed with miR-34a and let7; exploring its antitumor efficacy and the effect to block the cross-talking between miRNA and MYC/BCL2 pathway and to explore the deeper underlying molecular mechanism. This study will be significant on the application of miRNA replacement and oncolytic virus strategy in the DLBCL treatment, and has the potential theoretical and clinical application value in the research field of DLBCL.