circ_0001461/ miR-145-5p/ TFRC在宫颈癌患者中调控铁死亡及其预后价值  

circ_0001461/miR-145-5p/TFRC Regulation of Ferroptosis and the Prognostic Value in Cervical Cancer

作　　者：马晓蓉 谢群[1] 郭静[1] 万莉[1] Ma Xiaorong;Xie Qun;Guo Jing;Wan Li(Traditional Chinese Medicine Hospital Affiliated to Xinjiang Medical University Traditional Chinese Medicine of Xinjiang Uygur AutonomousRegion Institute,Urumqi 830000)

机构地区：[1]新疆医科大学附属中医医院新疆维吾尔自治区中医药研究院,乌鲁木齐830000

出　　处：《国际老年医学杂志》2024年第3期314-319,共6页International Journal of Geriatrics

基　　金：新疆维吾尔自治区自然科学基金项目(2019D01C182)。

摘　　要：目的 探索调控宫颈癌中铁死亡的环状核糖核酸(circRNAs)对开发新的治疗靶点的作用。方法 基于GSE102686、TCGA、GSE9750数据分析宫颈癌组和对照组之间的差异表达的circRNAs(DEcircRNAs)、差异表达的微小核糖核酸(DEmiRNAs)和差异表达的信使核糖核酸(DEmRNAs)。通过Starbase数据库预测与DEmiRNAs具有靶向调控关系的circRNAs、mRNAs,并与差异分析结果进行比较分析。对mRNAs进行富集分析以识别与细胞死亡(细胞周期、凋亡和铁死亡)相关的mRNAs,并构建相关竞争性内源性RNAs(ceRNAs)调控网络。通过单因素Cox回归分析识别显著影响患者预后的miRNAs和mRNAs。收集12例宫颈癌患者的宫颈癌组织及远处对照宫颈组织样本,利用定量逆转录聚合酶链反应(qRT-PCR)和蛋白免疫印记方法检测基因的表达,并利用双荧光素酶报告检测基因的靶向结合。结果宫颈癌和对照之间鉴定了179个DEcircRNAs、93个DEmiRNAs和739个DEmRNAs,并发现了160个DEcircRNAs, 565个DEmRNAs与DEmiRNAs有靶向关系。最终鉴定出circ_0001461/miR-145-5p/转铁蛋白受体(TFRC)的ceRNAs调控网络与铁死亡相关。circ_0001461、TFRC在宫颈癌组织中显著上调(P<0.05),miR-145-5p下调表达(P<0.05)。TFRC蛋白在宫颈癌组织中显著上调表达(P<0.05)。此外,miR-145-5p与circ_0001461和TFRC均具有靶向结合能力(P<0.05)。结论 circ_0001461/miR-145-5p/TFRC的ceRNAs网络调节铁死亡,并与宫颈癌患者的预后相关,可为宫颈癌患者提供新的治疗方法。Objective To explore circular RNAs(circRNAs)that regulate ferroptosis in cervical cancer,in the development of new therapeutic targets.Methods The differentially expressed circRNAs(DEcircRNAs),differentially expressed microRNAs(DEmiRNAs)and differentially expressed mRNAs(DEmRNAs)between cervical cancer and control groups were analyzed based on GSE102686,TCGA,GSE9750.circRNAs and mRNAs with targeted regulatory relationships with DEmiRNAs were predicted by the Starbase database and compared with differential analysis results.Enrichment analysis of mRNAs was performed to identify mRNAs associated with cell death(cell cycle,apoptosis,and iron death)and to construct relevant competitive endogenous RNAs(ceRNAs)regulatory networks.Univariate Cox regression analysis was performed to identify miRNAs and mRNAs that significantly affect patient outcomes.Cervical cancer tissues and distant control cervical tissue samples from 12 patients with cervical cancer were collected to detect gene expression using quantitative reverse transcription polymerase chain reaction(qRT-PCR)and Western blot,and targeted binding of genes was detected using a dual-luciferase reporter.Results A total of 179 DEcircRNAs,93 DEmiRNAs,and 739 DEmRNAs were identified between cervical cancer and controls,and 160 DEcircRNAs were found,and 565 DEmRNAs were targeted to DEmiRNAs.The ceRNAs regulatory network of circ_0001461/miR-145-5p/transferrin receptor(TFRC)was finally identified to be associated with ferroptosis.circ_0001461 and TFRC were significantly upregulated and miR-145-5p was downregulated in cervical cancer tissues(P<0.05).The protein expression of TFRC in cervical cancer tissues was significantly upregulated(P<0.05).In addition,miR-145-5p had target binding ability to both circ_0001461 and TFRC(P<0.05).Conclusion The ceRNAs network of circ_0001461/miR-145-5p/TFRC regulates ferroptosis and is associated with the prognosis of patients with cervical cancer,which may provide novel therapeutic approaches for patients with cervical cancer.

关 键 词：宫颈癌 竞争性内源性RNA网络 总体生存 铁死亡 

分 类 号：R737.33[医药卫生—肿瘤]