宫颈癌前病变组织中HPV感染与TLRs通路激活、下游基因表达的相关性

The correlation of HPV infection with TLRs pathway activation and downstream gene expression in cervical precancerous lesions

目的:研究宫颈癌前病变组织中HPV感染与TLRs通路激活、下游基因表达的相关性。方法:收集在新疆医科大学附属中医医院手术切除或锥切活检的宫颈癌前病变组织,根据高危型HPV感染情况分为HR-HPV阳性组、HR-HPV阴性组;另取同期在新疆医科大学附属中医医院因子宫肌瘤接受手术切除的正常宫颈组织作为对照组。测定宫颈癌前病变组织及正常宫颈组织中TLRs通路分子的含量、凋亡相关基因及侵袭相关基因的表达量。结果:HR-HPV阳性组、HR-HPV阴性组的病灶组织中TLR2、TLR3、TLR4、TLR9、NF-κB的含量以及CyclinD1、PCNA、iNOS、Gal-9、N-cadherin、HIF-1α、VEGF的mRNA表达量均显著高于对照组,p53、Beclin1、LC3-II、SFRP2的mRNA表达量均显著低于对照组(P<0.05),HR-HPV阳性组的病灶组织中TLR2、TLR3、TLR4、TLR9、NF-κB的含量以及CyclinD1、PCNA、iNOS、Gal-9、N-cadherin、HIF-1α、VEGF的mRNA表达量均显著高于HR-HPV阴性组,p53、Beclin1、LC3-II、SFRP2的mRNA表达量均显著低于HR-HPV阴性组(P<0.05)。结论:宫颈癌前病变组织中HPV感染能够通过激活多条TLRs通路来调节下游凋亡、侵袭基因的表达。

Objective：To study the correlation of HPV infection with TLRs pathway activation and downstream gene expression in cervical precancerous lesions.Methods：Cervical precancerous lesion tissues from surgical resection or cone biopsy in Affiliated Traditional Chinese Medicine Hospital of Xinjiang Medical University between June 2014 and May 2017 were collected and divided into HR-HPV positive group and HR-HPV negative group according to the condition of high-risk HPV infection;normal cervical tissues surgically removed due to fibroid in Affiliated Traditional Chinese Medicine Hospital of Xinjiang Medical University during the same period were collected as the control group.The contents of TLRs pathway molecules as well as the expression of apoptosis-related genes and invasion-related genes in the cervical precancerous lesion tissues and normal cervical tissues were determined.Results：TLR2,TLR3,TLR4,TLR9 and NF-κB contents as well as CyclinD1,PCNA,iNOS,Gal-9,N-cadherin,HIF-1αand VEGF mRNA expression in HR-HPV positive group and HR-HPV negative group were significantly higher than those in control group whereas p53,Beclin1,LC3-II and SFRP2 mRNA expression were significantly lower than those in control group（P〈0.05）,and TLR2,TLR3,TLR4,TLR9 and NF-κB contents as well as CyclinD1,PCNA,iNOS,Gal-9,N-cadherin,HIF-1αand VEGF mRNA expression in HR-HPV positive group were significantly higher than those in HR-HPV negative group whereas p53,Beclin1,LC3-II and SFRP2 mRNA expression were significantly lower than those in HR-HPV negative group（P〈0.05）.Conclusion：HPV infection in cervical precancerous lesions can regulate downstream apoptosis and invasion gene expression by activating multiple TLRs pathways.