Jiang Qing-ping, Liu Shao-yan, He Xiu-fang, Peng Juan, Xiong Han-zhen, Xiong Zhong-tang, Yang Yue-xin
Department of Pathology, Third Affiliated Hospital of Guangzhou Medical Collage, Guangzhou 510150, China.
Nan Fang Yi Ke Da Xue Xue Bao. 2011 Jun;31(7):1146-9.
To detect the expression of MAP3K5 and miR-BART22 encoded by Epstein-Barr virus and explore their relationship in nasopharyngeal carcinomas (NPCs).
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.
EBERs were positive in all the 53 NPC specimens, and miR-BART22 was positive in 49 specimens; 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).
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 to serve 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.
检测爱泼斯坦-巴尔病毒编码的MAP3K5和miR-BART22的表达,并探讨它们在鼻咽癌(NPC)中的关系。
收集53例存档的NPC标本和30例鼻咽炎标本,通过原位杂交检测EBERs和miR-BART22的表达,采用免疫组织化学检测MAP3K5的表达。还获取了10例新鲜的NPC和10例新鲜的鼻咽炎标本,通过蛋白质印迹法测定MAP3K5的蛋白表达。
53例NPC标本中EBERs均为阳性,49例miR-BART22为阳性;30例鼻咽炎标本EBER或miR-BART22均为阴性。在53例NPC组织中,50例癌区MAP3K5表达为阴性,但在相邻黏膜区为阳性,另外3例呈弱阳性(+)。在30例鼻咽炎标本中,25例MAP3K5呈强阳性,3例呈弱阳性,2例MAP3K呈阴性(P<0.001)。蛋白质印迹法显示,鼻咽炎中MAP3K5蛋白表达明显高于NPC组织(P=0.029)。MAP3K5和miR-BART22的表达呈负相关(P<0.001)。
与相邻黏膜组织相比,NPC组织中MAP3K5表达较低,但miR-BART22表达较高。MAP3K5和miR-BART22的表达呈负相关,提示MAP3K5有可能作为EBV miR-BART22的靶基因。miR-BART22可能抑制MAP3K5的表达,从而减少MAPK通路下游基因的蛋白磷酸化,抑制NPC细胞凋亡,阻止其分化并促进其逃避免疫监视。