mTORC1在EB病毒LMP1促进DLBCL细胞母细胞化的机制研究  

Mechanism about LMP1 of EB Virus Promoting Plasma Blast Diffe-rentiation of DLBCL Cell via mTORC1

作　　者：高晶晶[1] 朱雄鹏[2] 王明泉[1] 林兴智 庄燕玲 林宏峻 GAO Jing-Jing;ZHU Xiong Peng;WANG Ming-Quan;LIN Xing-Zhi;ZHUANG Yan-Ling;LIN Hong-Jun(Deparment of Blood Transfusion,Quanzhou First Hospital Afiliated to Fujian Medical University,Quanzhou 362000,Fujian Province,China;Deparment of Haematology,Quanzhou First Hospital Afiliated to Fujian Medical University,Quanzhou 362000,Fujian Province,China;Medical College of Huaqiao Universiry,Quanzhou 362000,Fujian Province,China)

机构地区：[1]福建医科大学附属泉州第一医院输血科,福建泉州362000 [2]福建医科大学附属泉州第一医院血液内科,福建泉州362000 [3]华侨大学医学院,福建泉州362000

出　　处：《中国实验血液学杂志》2024年第1期219-224,共6页Journal of Experimental Hematology

基　　金：泉州市科技项目(2021N057S);泉州市高层次人才创新创业项目(2019C003R)。

摘　　要：目的:研究通过mTORC1通路EB病毒LMP1诱导弥漫大B细胞淋巴瘤(DLBCL)细胞母细胞化的可能机制。方法:采用Western blot法分析EBV+及EBV-DLBCL细胞株LMP1蛋白、CD38的表达及p70S6K磷酸化情况。构建过表达LMP1稳转株及RNAi沉默LMP1基因,用RT-qPCR验证基因表达,并利用Western blot法检测各组细胞LMP1蛋白、CD38的表达量及较EBV-p70S6K磷酸化水平。结果:相较于EBV-DLBCL细胞,LMP1蛋白在EBV+DLBCL细胞上表达(P=0.0008),EBV+DLBCL细胞p70S6K磷酸化水平更高(P=0.0072)及CD38的表达量更高(P=0.0091)。与空载组对比,LMP1OE组的LMP1蛋白表达及CD38表达量均增高(P=0.0353;P<0.0001),且p70S6K磷酸化水平增高(P=0.0065);并验证了LMP1 mRNA表达(P<0.0001)。较si-NC组,LMP1KO组不表达LMP1蛋白(P=0.0129),且p70S6K磷酸化消失(P=0.0228);同时,CD38表达量减少,但无显著性差异(P=0.2377)。结论:LMP1通过活化mTORC1通路促进DLBCL细胞浆母细胞化。Objective:To investigate possible mechanism on protien LMP1 expressed by EBV inducing plasmablast differentiation of DLBCL cell via the mTORC1 pathway.Methods:The expression levels of LMP1 protein,CD38 and the phosphorylation levels of p70S6K in EBV~+and EBV~-DLBCL cell lines were detected by Western blot.Cell lines overexpressing LMP1 gene stablely were constructed and LMP1 gene was silenced by RNAi.The expression of LMP1 gene was verified by RT-qPCR.The expression levels of LMP1 and CD38 and the phosphorylation levels of p70S6K in each group were detected by Western blot.Results:Compared with EBV~-DLBCL cells,the expression of LMP1 was detected on EBV~+DLBCL cells(P=0.0008),EBV~+DLBCL cells had higher phosphorylation levels of p70S6K(P=0.0072)and expression levels of CD38(P=0.0091).Compared with vector group,the cells of LMP1~(OE)group had higher expression levels of LMP1 and CD38(P=0.0353;P<0.0001),meanwhile molecular p70S6K was phosphorylated much more(P=0.0065);expression of LMP1 mRNA was verified(P<0.0001).Compared with si-NC group,expression level of LMP1 protein(P=0.0129)was not detected and phosphorylated p70S6K disappeared of LMP1~(KO)group(P=0.0228);meanwhile,expression of CD38 decreased,although there was no significant difference(P=0.2377).Conclusion:LMP1 promotes DLBCL cells plasmablast differentiation via activating mTORC1 signal pathway.

关 键 词：EB病毒 潜伏膜蛋1 mTORC1通路 CD38 弥漫大B细胞淋巴瘤 浆母细胞化 

分 类 号：R733.1[医药卫生—肿瘤]