人巨细胞病毒通过STAT3上调胶质瘤中endocan表达

Human cytomegalovirus infection is involved in STAT3-upregulated endocan expression in gliomas

本研究旨在探讨人巨细胞病毒(human cytomegalovirus,HCMV)和内皮细胞特异性分子1(endocan)在胶质瘤发生发展中的作用及机制。利用HCMV感染人脑胶质瘤U87细胞,检测感染后第1、2、4天信号转导及转录激活蛋白3(signal transducer and activator of transcription 3,STAT3)和endocan的表达变化,并分析HCMV、STAT3和endocan三者之间的可能关联。结果显示,HCMV感染的U87细胞中pSTAT3和endocan表达上调,并随感染时间延长而逐渐升高;用RNAi干扰STAT3基因表达,endocan表达量下降;利用抗病毒药物更昔洛韦抑制HCMV复制后,pSTAT3表达量下降,endocan表达量随之下降。进一步利用免疫组织化学法检测79例脑胶质瘤患者和8例对照者脑组织中pSTAT3表达情况,发现pSTAT3在胶质瘤组织中表达上调;与低级别胶质瘤相比,高级别胶质瘤中pSTAT3染色强度较高。结果提示,HCMV感染可能通过STAT3信号通路上调endocan表达,从而参与胶质瘤的进展。

The aim of this study is to investigate the role of human cytomegalovirus （HCMV ） infection in glioma pathogenesis and its possible mechanism . Based on the previous experiments , the expressions of signal transducer and activator of transcription 3 （STAT3 ） and endocan in HCMV―infected U87 cells , a human glioma cell line , were detected , and the relationship among HCMV , STAT3 and endocan was analyzed .The results showed that HCMV infection induced the upregulation of endocan mRNA and protein as well as the activated STAT3 in U87 cells .On the other hand ,decreased levels of endocan mRNA and protein were observed in U87―STAT3―knockdown cells by RNAi . Furthermore , downregulated levels of endocan mRNA and protein were found in U87 cells treated by ganciclovir ,an anti―viral drug .Then the expression of pSTAT3 in 79 glioma specimens and 8 control brain tissues was detected by immunohistochemistry （IHC） and the relationship between pSTAT3 level and glioma grade was analyzed . Compared with the control brain samples ,increased level of pSTAT3 was found in glioma specimens and the staining intensity was related to glioma grade .The results suggest that HCMV infection is involved in glioma pathogenesis via upregulating endocan expression through STAT3 signaling pathway ,and further provide some new clues for the treatment of glioma .