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不明原因复发性流产中铁死亡的生物信息学分析及验证

张凤, 覃颖, 廖玉萍, 苏莎, 谭雪梅, 周卓琳, 黄世金, 钟琳琳, 冯春泉, 庞丽红

张凤, 覃颖, 廖玉萍, 苏莎, 谭雪梅, 周卓琳, 黄世金, 钟琳琳, 冯春泉, 庞丽红. 不明原因复发性流产中铁死亡的生物信息学分析及验证[J]. 广西医科大学学报, 2023, 40(5): 843-849. DOI: 10.16190/j.cnki.45-1211/r.2023.05.019
引用本文: 张凤, 覃颖, 廖玉萍, 苏莎, 谭雪梅, 周卓琳, 黄世金, 钟琳琳, 冯春泉, 庞丽红. 不明原因复发性流产中铁死亡的生物信息学分析及验证[J]. 广西医科大学学报, 2023, 40(5): 843-849. DOI: 10.16190/j.cnki.45-1211/r.2023.05.019
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Zhang Feng, Qin Ying, Liao Yuping, Su Sha, Tan Xuemei, Zhou Zhuolin, Huang Shijin, Zhong Linlin, Feng Chunquan, Pang Lihong. Bioinformatic analysis and validation of ferroptosis in unexplained recurrent spontaneous abortion[J]. Journal of Guangxi Medical University, 2023, 40(5): 843-849. DOI: 10.16190/j.cnki.45-1211/r.2023.05.019
Citation: Zhang Feng, Qin Ying, Liao Yuping, Su Sha, Tan Xuemei, Zhou Zhuolin, Huang Shijin, Zhong Linlin, Feng Chunquan, Pang Lihong. Bioinformatic analysis and validation of ferroptosis in unexplained recurrent spontaneous abortion[J]. Journal of Guangxi Medical University, 2023, 40(5): 843-849. DOI: 10.16190/j.cnki.45-1211/r.2023.05.019
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不明原因复发性流产中铁死亡的生物信息学分析及验证

  • 1. 广西医科大学第一附属医院产前诊断与遗传病诊断科, 南宁 530021;

  • 2. 贵港市人民医院产科, 贵港 537100;

  • 3. 广西医科大学第一附属医院妇产科, 南宁 530021;

  • 4. 广西中医药大学第一附属医院产科, 南宁 530012;

  • 5. 广西地中海贫血防治重点实验室, 南宁 530021;

  • 6. 国家卫生健康委地中海贫血防治重点实验室(广西医科大学), 南宁 530021;

  • 7. 广西医科大学区域性高发肿瘤早期防治研究教育部重点实验室, 南宁 530021;

  • 8. 广西区域性高发肿瘤早期防治研究重点实验室, 南宁 530021

基金项目: 

国家自然科学基金资助项目（No.81960281；No.82260306）；广西重点研发计划项目资助（No.桂科AB20159031）

详细信息
    通讯作者:

    冯春泉,E-mail:fengchunquan@126.com

    庞丽红,E-mail:panglihong@stu.gxmu.edu.cn

  • 中图分类号: R714.21

Bioinformatic analysis and validation of ferroptosis in unexplained recurrent spontaneous abortion

  • 1. Department of Prenatal Diagnosis and Genetic Diseases, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China;

  • 2. Department of Obstetrics, People's Hospital of Guigang City, Guigang 537100, China;

  • 3. Department of Obstetrics and Gynecology, The First Affiliated Hos-pital of Guangxi Medical University, Nanning 530021, China;

  • 4. Department of Obstetrics, The First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning 530012, China;

  • 5. Guangxi Key Laboratory of Thalassemia Research, Nanning 530021, China;

  • 6. NHC Key Laboratory of Thalassemia Medicine, Guangxi Medical University, Nanning 530021, China;

  • 7. Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Gaungxi Medical University, Ministry of Education, Nanning 530021, China;

  • 8. Guangxi Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Nanning 530021, China

摘要

    摘要
  • 摘要   目的：探究铁死亡关键基因在不明原因复发性流产（URSA）发生发展中的作用，初步确定潜在生物标志物。方法：从基因表达综合（GEO）数据库下载数据集GSE26787，利用GEO2R 筛选差异表达基因（DEGs）；从FerrDb V2数据库下载铁死亡相关基因；DEGs与铁死亡基因取交集获得URSA 铁死亡相关基因；利用DAVID 数据库对URSA 铁死亡相关基因进行基因本体（GO）富集及京都基因与基因组百科全书（KEGG）通路分析；利用String数据库和Cytoscape软件分析蛋白互作网络，筛选Hub基因；采用实时荧光定量PCR（RT-qPCR）检测Hub 基因在人工流产组及URSA 组患者蜕膜组织中mRNA 的表达水平。结果：共筛选出55 个URSA 铁死亡基因；GO 功能富集提示URSA 铁死亡相关基因主要在自噬调节、RNA 聚合酶Ⅱ启动子转录正调控、膜的整体组分、酶及p53蛋白受体结合富集。KEGG通路分析显示URSA铁死亡基因富集最明显的为FoXO信号通路。采用String 数据库及Cytoscape 软件筛选出的URSA 铁死亡关键基因分别为EGFR、SRC、KRAS、MDM2。RT-qPCR 检测结果显示，EGFR、SRC、MDM2在URSA 组中的表达均低于人工流产组（均P< 0.05）；KRAS在URSA 组和人工流产组中表达无统计学差异（P> 0.05）。结论：铁死亡相关基因EGFR、SRC、MDM2可作为诊治URSA的潜在生物标志物。
    Abstract   Objective:To explore the the role of key genes of ferroptosis in the occurrence and development of unexplained recurrent spontaneous abortion(UR-SA), and to preliminarily identify the potential bio-markers.Methods:The GSE26787 data set was downloaded from Gene Expression Synthesis (GEO)database, and the differentially expressed genes(DEGs)were screened by GEO2R, obtaining ferroptosis-related genes from FerrDb V2 database.The ferroptosisrelated genes in URSA were obtained by intersection of DEGs and ferroptosis genes.The gene ontology(GO)en-richment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of ferroptosis-related genes in URSA were performed using DAVID database.The protein interaction network was analyzed using String data-base and Cytascape software to screen the Hub genes.Real-time fluorescence quantitative polymerase chain reac-tion(RT-qPCR)was used to detect the mRNA expression levels of Hub genes in the decidua tissues of patients in the induced abortion group and the URSA group.Results:A total of 55 ferroptosis-related genes in URSA were screened.GO functional enrichment analysis found that ferroptosis-related genes in URSA were mainly enriched in the regulation of macroautophagy, positive regulation of transcription from RNA polymerase Ⅱpromoter, inte-gral components of the membrane and enzyme and p53 receptor binding.The enrichment analysis of KEGG path-way showed that the most obvious enrichment of ferroptosis-related genes in URSA was the FoxO signaling path-way.String database and Cytoscape software were used to screen the key genes of ferroptosis EGFR、SRC、KRAS、MDM2 in URSA.The results of RT-qPCR showed that the expressions of EGFR, SRC and MDM2 in the URSA group were lower than those in the induced abortion group(all P< 0.05).There was no statistically signifi-cant difference in the expression of KRAS between URSA group and induced abortion group (P> 0.05).Conclusion: Ferroptosis-related genes EGFR, SRC and MDM2 can be used as potential biomarkers for diagnosis and treatment of URSA.
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出版历程
  • 收稿日期:  2023-01-30
  • 网络出版日期:  2024-01-31
  • 刊出日期:  2023-05-01

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