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
高晶晶 1朱雄鹏 2王明泉 1林兴智 1庄燕玲 1林宏峻3
作者信息
- 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
- 折叠
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,LMP10E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.
Abstract
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 LMP1OE 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 LMP1KO 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Key words
EB virus/LMP1/mTORC1 pathway/CD38/DLBCL/plasmablast differentiation引用本文复制引用
基金项目
泉州市科技计划(2021N057S)
泉州市高层次人才创新创业项目(2019C003R)
出版年
2024
NETL
NSTL
维普
万方数据