miR-34a、HMGB1及PCNA在宫颈上皮内病变中的表达及其临床意义  

Expression and clinical significance of miR-34a HMGB1 and PCNA in the progression of squamous intraepithelial lesions

作　　者：万兵 梁月娟 王鹤[1] Wan Bing;Liang Yuejuan;Wang He(Department of Gynecology,Guangxi Medical University Affiliated Tumor Hospital,Nanning530021,China)

机构地区：[1]广西医科大学附属肿瘤医院妇瘤科,南宁530021

出　　处：《广西医科大学学报》2021年第4期783-789,共7页Journal of Guangxi Medical University

基　　金：2017年广西区域性高发肿瘤早期防治研究重点实验室专项基金资助项目(No.GKZ201613);广西医学高层次骨干人才“139”计划培养人选专项基金资助项目(No.G201903032);广西医疗卫生适宜技术开发与推广应用资助项目(No.S2018031)。

摘　　要：目的:探讨miR-34a、高迁移率族蛋白B1(HMGB1)及细胞增殖核抗原(PCNA)基因在宫颈上皮内病变(SIL)组织中的表达及其与临床病理因素的关系。方法:收集广西医科大学附属肿瘤医院2016年1月至2019年12月收治的158例SIL、宫颈鳞癌(SCC)及因子宫肌瘤/子宫腺肌症切除子宫的患者宫颈组织标本及临床病理资料。将研究对象分为正常宫颈组(n=50)、SIL组(n=65)和SCC组(n=43)。采用实时荧光定量PCR(qPCR)检测与分析miR-34a、HMGB1及PCNA在组织样本和细胞系中的表达。结果:SIL组和SCC组miR-34a表达均显著低于正常宫颈组(均P<0.001),且SCC组显著低于SIL组(P=0.024)。SCC组HMGB1 mRNA水平均显著高于正常宫颈组和SIL组(P=0.001,P=0.038),且SCC组显著高于SIL组(P=0.039)。SCC组PCNA mRNA水平均显著高于正常宫颈组和SIL组(P=0.033,P=0.004),而正常组和SIL组比较,差异无统计学意义(P=0.967)。H8细胞miR-34a表达显著高于SiHa细胞,而HMGB1和PCNA的mRNA水平显著低于SiHa细胞(P<0.001,P=0.005,P=0.045)。此外,HPV阳性的SIL和SCC组织miR-34a的m RNA水平均显著下调(P=0.028,P=0.039),有淋巴结转移者miR-34a表达显著下调(P=0.015)。结论:随着宫颈病变程度的加重,miR-34a表达逐渐降低,HMGB1和PCNA表达逐渐升高,三者的变化趋势预示着SIL的进展和宫颈癌(CC)的发生,miR-34a、HMGB1及PCNA有望成为预警SIL进展的新靶标。Objective:To investigate the expression of miR-34 a,HMGB1 and PCNA genes in squamous intraepithelial lesions(SIL)and their relationship with clinicopathological factors.Methods:Cervical tissue specimens and clinicopathological information of 158 patients with SIL,cervical squamous cell carcinoma(SCC)and hysterectomy due to hysteromyoma/adenomyosis were collected.The subjects were divided into normal cervical group(n=50),SIL group(n=65)and SCC group(n=43).The expressions of miR-34 a,HMGB1 and PCNA in tissue samples and cell lines were detected and analyzed by qRT-PCR.Results:The expression of miR-34 a in SIL group and SCC group was significantly lower than that in normal group(P<0.001),and that in SCC group was significantly lower than that in SIL group(P=0.024).The mRNA level of HMGB1 in normal group and SIL group was significantly lower than that in SCC group(P=0.001,P=0.038),and that in SIL group was significantly lower than that in SCC group(P=0.039).The mRNA levels of PCNA in normal group and SIL group were significantly lower than those in SCC group(P=0.033,P=0.004),but there was no significant difference between normal groupand SIL group(P=0.967).The expression of mi R-34 a in H8 cells was significantly higher than that in Si Ha cells,while the m RNA levels of HMGB1 and PCNA in H8 cells were significantly lower than those in SiHa cells(P<0.001,P=0.005,P=0.045).In addition,the m RNA levels of mi R-34 a in HPV positive SIL and SCC were significantly down regulated(P=0.028,P=0.039),and the expression of mi R-34 a in patients with lymph node metastasis was significantly down regulated(P=0.015).Conclusion:With the aggravation of cervical lesions,the expression of mi R-34 a gradually decreases,while the expression of HMGB1 and PCNA gradually increases.The change trend of the three indicates the progress of SIL and the occurrence of cervical cancer.Mi R-34 a,HMGB1 and PCNA are expected to become new targets for early warning the progress of SIL.

关 键 词：宫颈上皮内病变 宫颈癌 MIR-34A HMGB1 PCNA 

分 类 号：R737.33[医药卫生—肿瘤]