神经轴突诱导因子Semaphorin-3F逆转弥漫大B细胞淋巴瘤利妥昔单抗耐药的机制研究

弥漫大B细胞淋巴瘤（DLBCL）是最常见的非霍奇金淋巴瘤。我们前期发现神经轴突诱导因子SEMA3F可抑制肿瘤细胞的增殖及促进细胞凋亡，对GSE数据库进行深入分析时发现在接受含利妥昔单抗方案治疗的患者中，SEMA3F的表达与患者预后呈正相关关系，同时SEMA3F能够上调CD20的表达，提示SEMA3F可能具有逆转DLBCL患者对利妥昔单抗耐药的功能，但具体机制未见报道，且前期基因芯片结果提示SEMA3F的表达可影响Hippo信号通路的激活，推测SEMA3F可能通过Hippo信号通路逆转DLBCL的利妥昔单抗的耐药。本项目拟通过体内及体外实验证实SEMA3F对肿瘤细胞利妥昔单抗耐药的逆转作用，解析SEMA3F参与调控DLBCL利妥昔单抗耐药的分子机制，并评估其临床价值与治疗意义。研究结果将对于认识DLBCL的生物学特性具有重要意义，对探索更为有效的诊疗策略和改善患者预后提供新的思路。

Diffuse large B cell lymphoma is one of the most common non-Hodgkin lymphoma, Our previously study demonstrated that axon guidance factor semaphorin-3f (SEMA3F) could inhibit proliferation of tumor cells and promotes the apoptosis, results of GSE dataset suggested that expression of SEMA3F was positively correlated with survival of patients treated with R-CHOP regimens, meanwhile we found that SEMA3F could upregulate the expression of CD20, suggested that SEMA3F might abrogate the rituximab-resistance of patients, but the detailed underlying mechanism is rarely reported, results of RNA-seq suggested that SEMA3F could regulation the activation of hippo signaling pathway, the current proposal will bring forward that SEMA3F can abrogate DLBCL cell rituximab resistance via hippo pathway. We aim to demonstrate that SEMA3F can abrogate DLBCL cells rituximab resistance capacity in vitro. After in situ xenograft is established in nude mice, the effects of SEMA3F on rituximab resistance will be explored. Meantime, the impact hippo pathway on the biological effects mediated by SEMA3F will be investigated, and identify the molecular mechanism of SEMA3F on rituximab resistance, the significance of clinical diagnosis and therapeutic strategy. Our study will help the field to understand the biological characteristics of DLBCL, which will highlight the significance of novel and potential targets for future therapeutic approaches in cancer.