Department of Gynecology Oncology, The First Hospital of Jilin University, 71th Xinmin Road, Chang Chun, 130021, Jilin, China.
Department of Gynecology and Obstetric, The First Hospital of Jilin University, Chang Chun, 130021, Jilin, China.
Arch Gynecol Obstet. 2019 Apr;299(4):1089-1098. doi: 10.1007/s00404-018-5007-y. Epub 2019 Jan 4.
PURPOSE: We aimed to seek the crucial genes or microRNAs (miRNA) correlated with the cervical cancer development. METHODS: The miRNA profiling GSE30656 and gene expression profiling GSE63514 were obtained from Gene Expression Omnibus database. Differentially expressed microRNAs (DEMiRs) and differentially expressed genes (DEGs) were screened. Then target genes of DEMiRs were obtained and matched with DEGs to obtain interaction pairs between DEMiRs and DEGs. Gene Ontology-biological process and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted for DEGs and DEMiRs in the DEMiRs-DEGs pairs. The DEMiRs-DEGs regulatory network, protein-protein interaction network and transcription factor (TF)-target regulatory network were constructed. Ultimately, long non-coding RNAs (lncRNAs) associated with DEMiRs were obtained, and then lncRNA-miRNA-target ceRNA network was established. RESULTS: Total 18 DEMiRs and 620 DEGs were identified. DEMiRs were enriched in 35 KEGG pathways, such as PI3K-Akt signaling pathway (involving miR-451a). DEGs were enriched in various functions, such as DNA replication (involving E2F7) and angiogenesis (involving EREG). There were 120 nodes and 216 interaction pairs in the DEMIR-DEG regulatory network, and miR-106b-5p has the greatest degree. EREG and E2F7 were regulated by miR-451a and miR-148a-3p, respectively. Besides, E2F7 was identified in the TF-target regulatory network, regulating CDC6. There were 15 lncRNAs, 11 miRNAs and 90 DEGs in the ceRNA network. Specially, miR-148a-3p was interacted with lncRNA HOTAIR in the ceRNA network. CONCLUSION: E2F7, EREG, miR-451a and miR-106b-5p were likely to be related to the cervical cancer development.
目的:我们旨在寻找与宫颈癌发展相关的关键基因或 microRNA(miRNA)。
方法:从基因表达综合数据库中获取 miRNA 谱 GSE30656 和基因表达谱 GSE63514。筛选差异表达 microRNA(DEMiRs)和差异表达基因(DEGs)。然后获得 DEMiRs 的靶基因,并与 DEGs 匹配,以获得 DEMiRs 和 DEGs 之间的相互作用对。对 DEMiRs-DEGs 对中的 DEGs 和 DEMiRs 进行基因本体论生物过程和京都基因与基因组百科全书(KEGG)通路富集分析。构建 DEMiRs-DEGs 调控网络、蛋白质-蛋白质相互作用网络和转录因子(TF)-靶调控网络。最终,获得与 DEMiRs 相关的长链非编码 RNA(lncRNA),并建立 lncRNA-miRNA-靶 ceRNA 网络。
结果:共鉴定出 18 个 DEMiRs 和 620 个 DEGs。DEMiRs 富集在 35 个 KEGG 通路中,如 PI3K-Akt 信号通路(涉及 miR-451a)。DEGs 富集在各种功能中,如 DNA 复制(涉及 E2F7)和血管生成(涉及 EREG)。在 DEMIR-DEG 调控网络中,有 120 个节点和 216 个相互作用对,其中 miR-106b-5p 的度数最大。EREG 和 E2F7 分别受 miR-451a 和 miR-148a-3p 的调控。此外,E2F7 在 TF-靶调控网络中被鉴定出,调节 CDC6。ceRNA 网络中存在 15 个 lncRNA、11 个 miRNA 和 90 个 DEG。特别是,miR-148a-3p 在 ceRNA 网络中与 lncRNA HOTAIR 相互作用。
结论:E2F7、EREG、miR-451a 和 miR-106b-5p 可能与宫颈癌的发展有关。
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