E2F7, EREG, miR-451a and miR-106b-5p are associated with the cervical cancer development

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.

Keywords: Angiogenesis; Cervical cancer; Differentially expressed genes; Differentially expressed miRNAs; Regulatory network.

MeSH terms

  • E2F7 Transcription Factor / physiology*
  • Epiregulin / physiology*
  • Female
  • Gene Regulatory Networks
  • Humans
  • MicroRNAs / physiology*
  • Uterine Cervical Neoplasms / etiology*
  • Uterine Cervical Neoplasms / genetics


  • E2F7 Transcription Factor
  • E2F7 protein, human
  • EREG protein, human
  • Epiregulin
  • MIRN106 microRNA, human
  • MIRN451 microRNA, human
  • MicroRNAs