The role of Mitogen-and Stress-Activated Kinase 1 in Epstein-Barr virus latent membrane protein-1-pr

• 作 者: BinbinLi[1]ZhengWan[2]GuoliangHuang[2]XiangningZhang[3]HuaChen[2]JianWang[2]ZhiweiHe[1]
• 机 构: Department of Pathophysiology,Guangdong Medical College,Guangdong,No.1 Xincheng Road,Dongguan 523808
• 出 处: 中国病理生理学会第十四届肿瘤专业委员会、第十五届免疫专业委员会联合学术会议
• 发表日期: 2014年期

　　Objective: The Mitogen-and Stress-Activated Kinase 1(MSK1)-mediated nucleosomal response plays a critical role in connecting extracellular signals with gene expression.However,the role of MSK1 in malignant transformation and cancer development is not well understood.Here,we aimed to explore the role of MSK1 in Epstein-Barr virus (EBV) latent membrane protein-1 (LMP1)-promoted cell proliferation and transformation of nasopharyngeal carcinoma (NPC) cells and its regulatory mechanism.Methods: The expression of p-MSKl(Thr581) was detected by the immunohisto-chemical analysis in NPC tissue and normal nasopharynx tissues,and its correlation with LMP1 was analyzed in NPC tissues and cell lines.Using the small interfering RNA (siRNA)-MSK1,the role of MSK1 in LMP1-promoted CNE1 cell proliferation and transformation were evaluated by CCK-8 assay,flow cytometry and focus-forming assay respectively.Furthermore,the regulation of MSK1 on LMP1-induced AP-1 activation and expressions of Fra-1,Bcl-2 and Hsp27 were examined by reporter gene assay and western blotting.Results: Immunohistochemical analysis revealed that the expression of p-MSK1 (Thr581) was significantly higher in the poorly differentiated NPC tissues than that in normal nasopharynx tissues (p <0.001).Moreover,high level of p-MSK1 was positively correlated with the expression of LMP1 in NPC tissues (x2=9.600,p =0.002;C=0.408).LMP1 could increase the level of MSK1 phosphorylation at Thr581 in CNE1 cells.The knockdown of MSK1 with small interfere RNA-MSK1 suppressed LMP1-promoted CNE1 ceil proliferation,which was associated with impaired G1-S cell cycle transition.In addition,the ability of colony formation promoted by LMP1 was blocked by MSK1 inhibitor H89 or knockdown of MSK1.When MSK1 activity or expression was inhibited,the AP-1 activity and expressions of Fra-1,Bcl-2 and Hsp27 induced by LMP1 were greatly reduced.Conclusion: Increasing MSK1 activity is critically important for LMP1-promoted CNE1 cell proliferation and transformation,which may correlated with its induction of aberrant gene expression.