Integrated analysis of ceRNA network in hepatocellular carcinoma using bioinformatics analysis

Medicine (Baltimore). 2021 Jun 4;100(22):e26194. doi: 10.1097/MD.0000000000026194.

Abstract

Background: Long noncoding RNAs (lncRNAs) can work as microRNA (miRNA) sponges through a competitive endogenous RNA (ceRNA) mechanism. LncRNAs and miRNAs are important components of competitive endogenous binding, and their expression imbalance in hepatocellular carcinoma (HCC) is closely related to tumor development, diagnosis, and prognosis. This study explored the potential impact of the ceRNA regulatory network in HCC on the prognosis of HCC patients.

Methods: We thoroughly researched the differential expression profiles of lncRNAs, miRNAs, and mRNAs from 2 HCC Gene Expression Omnibus datasets (GSE98269 and GSE60502). Then, a dysregulated ceRNA network was constructed by bioinformatics. In addition, hub genes in the ceRNA network were screened by Cytoscape, these hub genes functional analysis was performed by gene set enrichment analysis, and the expression of these hub genes in tumors and their correlation with patient prognosis were verified with Gene Expression Profiling Interactive Analysis.

Results: A ceRNA network was successfully constructed in this study including 4 differentially expressed (DE) lncRNAs, 7 DEmiRNAs, and 166 DEmRNAs. Importantly, 4 core genes (CCNA2, CHEK1, FOXM1, and MCM2) that were significantly associated with HCC prognosis were identified.

Conclusions: Our study provides comprehensive and meaningful insights into HCC tumorigenesis and the underlying molecular mechanisms of ceRNA. Furthermore, the specific ceRNAs can be further used as potential therapeutic targets and prognostic biomarkers for HCC.

MeSH terms

  • Adult
  • Biomarkers, Tumor / metabolism
  • Carcinogenesis / genetics
  • Carcinoma, Hepatocellular / diagnosis
  • Carcinoma, Hepatocellular / genetics*
  • Checkpoint Kinase 1 / genetics
  • Computational Biology / methods*
  • Cyclin A2 / genetics
  • Female
  • Forkhead Box Protein M1 / genetics
  • Gene Expression Profiling / methods
  • Gene Expression Regulation, Neoplastic / genetics*
  • Humans
  • Liver Neoplasms / pathology*
  • Male
  • MicroRNAs / genetics
  • Middle Aged
  • Minichromosome Maintenance Complex Component 2 / genetics
  • Prognosis
  • RNA, Long Noncoding / genetics*
  • RNA, Messenger / genetics
  • RNA-Binding Motifs / genetics

Substances

  • Biomarkers, Tumor
  • CCNA2 protein, human
  • Cyclin A2
  • FOXM1 protein, human
  • Forkhead Box Protein M1
  • MicroRNAs
  • RNA, Long Noncoding
  • RNA, Messenger
  • CHEK1 protein, human
  • Checkpoint Kinase 1
  • MCM2 protein, human
  • Minichromosome Maintenance Complex Component 2