基于转录组测序分析宫颈病变中人乳头状瘤病毒16感染对泛素蛋白连接酶、核因子-κB表达的影响  

Effect of HPV16infection on the expression of UBC and NF-κB in cervical lesions based on transcriptome sequencing

作　　者：马敏丽 美力班.吐尔逊 王振芳 阿仙姑.哈斯木 MA Minli;Meiliban Tuerxun;WANG Zhenfang;Axiangu Hasimu(Graduate School, Xinjiang Medical University, Urumqi 830011 ,China;No. 474 People＇s Liberation Army Hospital, Urumqi 830013;Department of Pathology and Anatomy, School of Pre clinical Medicine, Xinjiang Medical University, Urumqi 880011, China)

机构地区：[1]新疆医科大学研究生学院,乌鲁木齐830011 [2]解放军第四七四医院病理科,乌鲁木齐830013 [3]新疆医科大学基础医学院病理解剖学教研室,乌鲁木齐830011

出　　处：《新疆医科大学学报》2018年第5期534-538,共5页Journal of Xinjiang Medical University

基　　金：新疆维吾尔自治区自然科学基金-联合基金(2017D01C227)

摘　　要：目的探讨新疆妇女宫颈病变中Toll样受体9(TLR9)和泛素蛋白连接酶(UBC)、核因子-κB(NF-κB)表达与人乳头状瘤病毒16(HPV16)感染的关系。方法以人乳头瘤病毒(HPV)分型基因芯片检测86例慢性宫颈炎、宫颈上皮内瘤变(CIN)和宫颈癌组织HPV感染及分型;Illumina Hiseq测序平台对15例宫颈病变组织进行转录组测序;通过免疫组化SP法检测TLR9、UBC和NF-κB在慢性宫颈炎、CINⅡ-Ⅲ和宫颈癌患者石蜡包埋组织中的表达水平。结果宫颈癌的HPV感染率为100%(41/41),CINⅡ-Ⅲ的感染率为60%(15/25),慢性宫颈炎的感染率为15%(3/20),其中HPV16为主要感染型别;转录组测序结果显示,HPV16阳性的宫颈癌和CINⅡ-Ⅲ组织中与TLR9相关的差异上调表达的基因有12个(NF-κB、UBC、TICAM1、POU2F3、S100A8、NOD2、CDK1、FOS、JUN、MAL、IRF7和RP11-58O9.2);免疫组化结果显示TLR9、UBC和NF-κB在CIN和宫颈癌组织中高表达,其表达水平呈正相关(r分别为0.510和0.469,P值均<0.001)。结论在宫颈癌发展过程中,HPV16感染可能通过泛素-蛋白酶体降解途径影响TLR9蛋白表达,具体调控机制需要深入研究。Objective To investigate the relationship between the expressions of Toll-like receptor 9（TLR9）,Ubiquitin ligases（UBC）,Nuclear factor-κB（NF-κB）and human papilloma-virus（HPV）16 in cervical lesions of Xinjiang women.Methods Eighty-six cases of Uyghur chronic cervicitis,cervical intraepithelial neoplasia（CIN）and cervical cancer HPV infection and typing were detected by HPV typing gene chip;Illumina Hiseq sequencing platform was used for transcriptome sequencing of 15 cervical lesion tissues.The expression of TLR9,UBC and NF-κB in paraffin-embedded tissues of patients with chronic cervicitis,CIN Ⅱ-Ⅲ and cervical cancer were detected by immunohistochemical SP method.Results The HPV infection rate of cervical cancer was 100%（41/41）,the infection rate of CIN Ⅱ-Ⅲ was 60%（15/25）,and the infection rate of chronic cervicitis was 15%（3/20）,of which HPV16 was the major infection type.Transcriptome sequencing results showed that there were 12 TLR9-related different up-regulated genes（TLR9,NF-κB,UBC,TICAM1,POU2 F3,S100 A8,NOD2,CDK1,FOS,JUN,MAL and IRF7）in HPV16-positive cervical cancer and CIN Ⅱ-Ⅲ tissue.Immunohistochemistry results showed that TLR9,UBC9 and NF-κB were highly expressed in CIN and cervical cancer tissues,and their expression levels were positively correlated（r =0.510 and 0.469,P〈0.001,respectively）.Conclusion HPV16 infection may affect the expression of TLR9 protein in women through the ubiquitin-proteasomal degradation pathway,in which the specific regulatory mechanisms need to be further studied.

关 键 词：宫颈癌 人乳头状瘤病毒16 TOLL样受体9 泛素蛋白连接酶 核因子-ΚB 

分 类 号：R737.33[医药卫生—肿瘤]