缺氧对宫颈癌SiHa细胞中Gli1与Sox2表达的影响  

Effect of hypoxia on expressions of Gli1 and Sox2 in cervical cancer SiHa cells

作　　者：朱长吉 刘兴哲 玄延花[1] ZHU Changji;LIU Xingzhe;XUAN Yanhua(Department of Pathology,Yanbian University College of Medicine,Yanji 133002,China)

机构地区：[1]延边大学医学院病理教研室,吉林延吉133002

出　　处：《吉林大学学报（医学版）》2024年第2期442-450,共9页Journal of Jilin University：Medicine Edition

基　　金：国家自然科学基金项目(82160594)。

摘　　要：目的:分析胶质瘤相关癌基因同源物1(Gli1)和性别决定区Y框蛋白2(Sox2)在宫颈癌细胞中的表达及其病理学意义,探讨Gli1与宫颈癌干性特征的相关性。方法:采用免疫组织化学染色方法检测159例宫颈癌组织中Gli1、缺氧诱导因子1α(HIF-1α)、Sox2、性别决定区Y框蛋白9(Sox9)、分化簇44(CD44)、八聚体结合转录因子4(OCT4)和赖氨酸特异性去甲基化酶1(LSD1)的表达并分析其相关性;使用基因表达谱数据动态分析(GEPIA)明确Gli1对宫颈癌状细胞患者预后的影响及其与干细胞标志物的相关性;缺氧条件下检测SiHa细胞的球体形成能力及其干细胞标志物表达。结果:免疫组织化学染色,在宫颈癌组织中Gli1表达率与HIF-1α(r=0.374,P<0.001)和Sox2表达水平(r=0.176,P<0.05)呈正相关关系;GEPIA数据库分析,宫颈癌中Gli1阳性表达的患者预后差(P<0.05)。缺氧条件下SiHa细胞中Gli1、HIF-1α和Sox2的mRNA及蛋白表达水平均明显升高(P<0.001),且具有较强的球体形成能力。结论:缺氧上调宫颈癌细胞Gli1和Sox2 mRNA及蛋白表达水平,促进癌细胞的干性特征形成。Objective:To analyze the expressions of glioma-associated oncogene homolog 1(Gli1)and sex determining region Y 2(Sox2)in the cervical cancer cells and their pathological significances,and to discuss the correlation between the expression of Gli1 and the stemness characteristics of the cervical cancer.Methods:Immunohistochemical staining was used to detect the expression of Gli1,hypoxia-inducible factor 1-alpha(HIF-1α),Sox2,sex determining region Y 9(Sox9),cluster of differentiation 44(CD44),octamer-binding transcription factor 4(OCT4),and lysine-specific demethylase 1(LSD1)in 159 cases of cervical cancer tissues and their correlations were analyzed.Gene Expression Profiling Interactive Analysis(GEPIA)was used to clarify the effect of Gli1 expression on the prognosis of the patients with cervical carcinoma and its correlation with the stem cell markers.The sphere-forming ability and the expression of stem cell markers in the SiHa cells under hypoxic status were detected.Results:The immunohistochemical staining results showed that the expression rate of Gli1 in cervical cancer tissue was positively correlated with the expression level of HIF-1α(r=0.374,P<0.001)and the expression level of Sox2(r=0.176,P<0.05).The GEPIA Database analysis results showed that the cervical cancer patients with positive Gli1 expression had poor prognosis(P<0.05).Under hypoxic status,the expression levels of Gli1,HIF-1α,and Sox2 mRNA and proteins in the SiHa cells were significantly increased(P<0.001),and the cells exhibited a strong sphere-formation ability.Conclusion:Hypoxia upregulates the expression levels of Gli1 and Sox2 mRNA and protein in the cervical cancer cells,and promotes the formation of stemness characteristics of the cancer cells.

关 键 词：宫颈肿瘤 胶质瘤相关癌基因同源物1 缺氧 干性 缺氧诱导因子1A 

分 类 号：R737.33[医药卫生—肿瘤]