Bioinformatics-based identification of miRNA-, lncRNA-, and mRNA-associated ceRNA networks and potential biomarkers for preeclampsia

Medicine (Baltimore). 2020 Nov 6;99(45):e22985. doi: 10.1097/MD.0000000000022985.

Abstract

This study aimed to identify significantly altered long non-coding RNAs (lncRNAs), microRNAs (miRNAs), mRNAs, pathways in preeclampsia (PE), and to investigate their targeted relationships and biological functions.GSE96985 from Gene Expression Omnibus database was extracted, involving 3 PE and 4 normal tissues. After the differential expression analysis of miRNAs, lncRNAs, and mRNAs using the limma package, protein-protein interaction (PPI) network and module analyses were performed for differentially expressed mRNAs (dif-mRNAs). Combined with the miRanda and miRWalk tools, a regulatory relationship between dif-miRNAs and dif-mRNAs/lncRNAs (dif-mRNAs/dif-lncRNAs) was predicted. Finally, mRNA-miRNA-lncRNA regulatory network construction was performed using Cytoscape software.A total of 511 dif-mRNAs were screened in PE. The top 5 nodes in the PPI networks included up-regulated complement component 3 (C3), C-X-C motif chemokine ligand 8 (CXCL8), and fibronectin 1 (FN1). Three significant network modules were identified for dif-mRNAs. C3 and CXCL8 were identified in module A, and FN1 was identified in module C. A disintegrin and metalloproteinase with thrombospondin motifs 6 (ADAMTS6) was down-regulated by the miR-210-3p. Therefore, lnc-CTD-2383M3.1 functions as a competing endogenous RNA in ADAMTS6 expression regulation by competitively binding to miR-210-3p during the regulation process of PE.C3, CXCL8, FN1, and ADAMTS6 might be involved in the development of PE. The lnc-CTD-2383M3.1-miR-210-3p-ADAMTS6 axis might be a potential regulatory mechanism in PE.

MeSH terms

  • ADAMTS Proteins / genetics
  • Biomarkers / metabolism
  • Complement C3 / genetics
  • Datasets as Topic
  • Down-Regulation
  • Female
  • Fibronectins / genetics
  • Gene Expression Profiling
  • Gene Regulatory Networks*
  • Humans
  • Interleukin-8 / genetics
  • MicroRNAs / metabolism*
  • Pre-Eclampsia / genetics*
  • Pregnancy
  • RNA, Long Noncoding / metabolism*
  • RNA, Messenger / metabolism*
  • Up-Regulation

Substances

  • Biomarkers
  • C3 protein, human
  • CXCL8 protein, human
  • Complement C3
  • FN1 protein, human
  • Fibronectins
  • Interleukin-8
  • MicroRNAs
  • RNA, Long Noncoding
  • RNA, Messenger
  • ADAMTS Proteins
  • Adamts6 protein, human