摘要
目的筛选并验证宫颈鳞状细胞癌(cervical squamous cell carcinoma,CESC)潜在的miRNA预后标志物,初步探究CESC发生的分子机制。方法利用TCGA数据库中宫颈鳞状细胞癌组织和癌旁组织的miRNA测序信息及患者临床数据,通过生物信息学分析,构建了由4个miRNAs(miR-505-5p、miR-142-3p、miR-532-5p、miR-218-1-3p)组成的预测宫颈鳞状细胞癌患者预后的风险模型并进行诊断效果评价,同时应用逆转录-聚合酶链反应(RT-PCR)检测21对CESC组织及癌旁正常组织中该4个miRNAs的表达水平,以差异表达显著的miR-505-5p作为研究对象,分析其表达水平与CESC患者各临床病理特征间的关系。在CESC细胞中转染miR-505-5p mimics后通过细胞实验探究miR-505-5p对CESC细胞功能的影响;最后通过生物信息法预测miR-505-5p的可能靶基因,并通过RT-PCR及Western blot实验进行验证。结果通过对TCGA数据库中宫颈鳞状细胞癌相关数据的分析,构建了由4个miRNAs(miR-505-5p、miR-142-3p、miR-532-5p、miR-218-1-3p)组成的预后风险模型,预后风险模型能有效地将CESC患者分为预后不良的高风险组和低风险组;miR-505-5p在收集到的21对CESC组织中的表达低于癌旁组织(P<0.05),其表达量与CESC患者的临床分期和侵袭程度负相关;过表达miR-505-5p后抑制了宫颈鳞状细胞癌SiHa细胞的增殖(P<0.05)、迁移,促进了凋亡(P<0.05);TBL1XR1作为miR-505-5p的最佳预测靶基因,过表达miR-505-5p后TBL1XR1的RNA水平及蛋白水平下降(P<0.05)。结论miR-505-5p可作为CESC患者的潜在预后标志物,在CESC中miR-505-5p可能通过靶向TBL1XR1发挥抑癌作用。
Objective To screen and verify the potential prognostic markers of miRNA in cervical squamous cell carcinoma(CESC),and to explore the molecular mechanism of CESC.Methods Using miRNA sequencing data of cervical squamous cell carcinoma tissues and adjacent tissues in the TCGA database,as well as patient clinical data,a risk model for predicting the prognosis of cervical squamous cell carcinoma patients was constructed using bioinformatics analysis.The model consists of four miRNAs(miR-505-5p,miR-142-3p,miR-532-5p,miR-218-1-3p).The diagnostic performance of the model was evaluated.Reverse transcription-polymerase chain reaction(RT-PCR)was used to detect the expression levels of these four miRNAs in 21 pairs of cervical squamous cell carcinoma tissues and adjacent normal tissues.MiR-505-5p,which showed significant differential expression,was selected for further analysis to examine its relationship with various clinical pathological features of cervical squamous cell carcinoma patients.Transfection of miR-505-5p mimics into cervical squamous cell carcinoma cells was performed to investigate the impact of miR-505-5p on the cellular functions of cervical squamous cell carcinoma.Finally,potential target genes of miR-505-5p were predicted using bioinformatics methods and validated through RT-PCR and Western blot experiments.Results By analyzing the cervical squamous cell carcinoma(CESC)related data from the TCGA database,a prognostic risk model composed of 4 miRNAs(miR-505-5p,miR-142-3p,miR-532-5p,miR-218-1-3p)was constructed.The prognostic risk model effectively stratifies CESC patients into high-risk and low-risk groups for adverse prognosis.The expression of miR-505-5p in the collected 21 pairs of CESC tissues was lower than that in adjacent tissues(P<0.05),and its expression level was negatively correlated with the clinical stage and invasion degree of CESC patients.Overexpression of miR-505-5p inhibited the proliferation(P<0.05)and migration of cervical squamous cell carcinoma SiHa cells,and promoted apoptosis(P<0.0
作者
颜怡君
杨宏英
张红平
李政
贾岳
赵敏
YAN Yijun;YANG Hongying;ZHANG Hongping;LI Zheng;JIA Yue;ZHAO Min(Dept.of Nuclear Medicine,Affiliated Hospital of Yunnan University,Kunming Yunnan 650021;Dept.of Gynecology,The Third Affiliated Hospital of Kunming Medical University,Kunming Yunnan 650118,China;Dept.of Medical Administration,The Third Affiliated Hospital of Kunming Medical University,Kunming Yunnan 650118,China)
出处
《昆明医科大学学报》
CAS
2023年第8期14-26,共13页
Journal of Kunming Medical University
基金
云南省科技厅-昆明医科大学应用基础研究联合专项基金资助项目(202201AY070001-167)
云南省教育厅科学研究基金资助项目(2022J0144)
云南省妇科肿瘤精准防治研究和应用推广创新团队项目(202305AS350020)。
