鼻咽癌中MAP3K5和Epstein-Barr病毒编码的miR-BART22表达的关系及意义  

Relationship between MAP3K5 and Epstein-Barr virus-encoded miR-BART22 expression in nasopharyngeal carcinoma

作　　者：江庆萍[1] 刘少颜[1] 何秀芳[2] 彭娟[1] 熊汉真 熊中堂[1] 杨嶽鑫 

机构地区：[1]广州医学院第三附属医院病理科,广东广州510150 [2]中山市人民医院耳鼻喉科,广东中山528403

出　　处：《南方医科大学学报》2011年第7期1146-1149,共4页Journal of Southern Medical University

基　　金：国家自然科学基金委与广东省联合基金(u0732006);广州市科技和信息化局基金(2010Y1-C231)~~

摘　　要：目的研究鼻咽癌中MAP3K5和Epstein-Barr病毒编码的miR-BART22的表达及其相关性。方法收集53例鼻咽癌石蜡档案标本和30例鼻咽黏膜慢性炎标本,分别行EBER和miR-BART22原位杂交及MAP3K5免疫组化检测;另分别选取10例鼻咽癌和鼻咽黏膜新鲜标本提取蛋白行MAP3K5的Western blot检测。结果 53例鼻咽癌EBER均阳性,49例miR-BART22阳性;30例鼻咽黏膜慢性炎EBER和miR-BART22均阴性。MAP3K5在53例鼻咽癌组织中50例为阴性,癌巢周围粘膜组织呈阳性表达,3例弱阳性(+)表达。30例鼻咽粘膜慢性炎中,25例强阳性表达(++～+++),3例弱阳性(+)表达,2例阴性;鼻咽癌和鼻咽黏膜慢性炎MAP3K5差异具有统计学意义(P<0.001);Westernblot检测结果黏膜慢性炎MAP3K5蛋白表达值高于鼻咽癌(P=0.029)。MAP3K5和miR-BART22表达呈负相关(P<0.001)。结论 MAP3K5在鼻咽癌组织中表达水平低于黏膜上皮组织。MiR-BART22与之相反,在鼻咽癌中高表达,而黏膜慢性炎中缺乏。MAP3K5和miR-BART22在鼻咽癌中表达呈负相关。根据以上实验和相关文献,我们推测MAP3K5可能是EB病毒miR-BART22靶标基因,EB病毒miR-BART22通过抑制MAP3K5的表达,使相应磷酸化MAP3K5蛋白减少,进而下调MAPK通路下游基因蛋白的磷酸化,并行使对NPC细胞抑制凋亡、阻止分化并促进免疫逃逸等作用。Objective To detect the expression of MAP3K5 and miR-BART22 encoded by Epstein-Barr virus and explore their relationship in nasopharyngeal carcinomas（NPCs）.Methods Fifty-three archived specimens of NPCs and 30 nasopharyngitis specimens were collected for detecting the expression of EBERs and miR-BART22 by in situ hybridization,and the expression of MAP3K5 was detected using immunohistochemistry.Ten fresh NPC and 10 fresh nasopharyngitis specimens were also obtained for determining the protein expression of MAP3K5 by Western blotting.Results EBERs were positive in all the 53 NPC specimens,and miR-BART22 was positive in 49 specimnes;all the 30 nasopharyngitis specimens were negative for EBER or miR-BART22.In the 53 NPC tissues,50 were negative for MAP3K5 expression in the cancer areas but positive in the adjacent mucosal areas,with the other 3 specimens showing a weak positivity（＋）.In the 30 nasopharyngitis specimens,25 showed strong MAP3K5 positivity,3 showed weak positivity and 2 were negative for MAP3K5（P〈0.001）.Western blotting showed that the expression of MAP3K5 protein was significantly higher in nasopharyngitis than in NPC tissues（P=0.029）.The expression of MAP3K5 and miR-BART22 was inversely correlated（P〈0.001）.Conclusion Compared with the adjacent mucosal tissues,NPC tissues have a lower expression of MAP3K5 but a higher expression of miR-BART22.The expression of MAP3K5 and miR-BART22 is inversely correlated,suggesting the possibility of MAP3K5 toserve as target gene of EBV miR-BART22.miR-BART22 may inhibit the expression of MAP3K5,thus reducing the protein phosphorylation of MAPK pathway downstream genes,inhibiting NPC cell apoptosis,preventing their differentiation and promoting their escape from immune surveillance.

关 键 词：鼻咽癌 MAP3K5 EPSTEIN-BARR病毒 miR-BART22 MIRNA 

分 类 号：R739.63[医药卫生—肿瘤]