Integrated analysis of lncRNA-miRNA-mRNA ceRNA network in squamous cell carcinoma of tongue

BMC Cancer. 2019 Aug 7;19(1):779. doi: 10.1186/s12885-019-5983-8.

Abstract

Background: Numerous studies have highlighted that long non-coding RNAs (lncRNAs) can bind to microRNA (miRNA) sites as competing endogenous RNAs (ceRNAs), thereby affecting and regulating the expression of mRNAs and target genes. These lncRNA-associated ceRNAs have been theorized to play a significant role in cancer initiation and progression. However, the roles and functions of the lncRNA-miRNA-mRNA ceRNA network in squamous cell carcinoma of the tongue (SCCT) are still unclear.

Methods: The miRNA, mRNA and lncRNA expression profiles from 138 patients with SCCT were downloaded from The Cancer Genome Atlas database. We identified the differential expression of miRNAs, mRNAs, and lncRNAs using the limma package of R software. We used the clusterProfiler package for GO and KEGG pathway annotations. The survival package was used to estimate survival analysis according to the Kaplan-Meier curve. Finally, the GDCRNATools package was used to construct the lncRNA-miRNA-mRNA ceRNA network.

Results: In total, 1943 SCCT-specific mRNAs, 107 lncRNAs and 100 miRNAs were explored. Ten mRNAs (CSRP2, CKS2, ADGRG6, MB21D1, GMNN, RIPOR3, RAD51, PCLAF, ORC1, NAGS), 9 lncRNAs (LINC02560, HOXC13 - AS, FOXD2 - AS1, AC105277.1, AC099850.3, STARD4 - AS1, SLC16A1 - AS1, MIR503HG, MIR100HG) and 8 miRNAs (miR - 654, miR - 503, miR - 450a, miR - 379, miR - 369, miR - 190a, miR - 101, and let-7c) were found to be significantly associated with overall survival (log-rank p < 0.05). Based on the analysis of the lncRNA-miRNA-mRNA ceRNA network, one differentially expressed (DE) lncRNA, five DEmiRNAs, and three DEmRNAs were demonstrated to be related to the pathogenesis of SCCT.

Conclusions: In this study, we described the gene regulation by the lncRNA-miRNA-mRNA ceRNA network in the progression of SCCT. We propose a new lncRNA-associated ceRNA that could help in the diagnosis and treatment of SCCT.

Keywords: Competing endogenous RNAs network; Long non-coding RNAs; Overall survival; Squamous cell carcinoma of the tongue; The Cancer genome atlas.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / pathology
  • Computational Biology / methods
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Gene Ontology
  • Gene Regulatory Networks*
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • Neoplasm Staging
  • RNA, Long Noncoding / genetics*
  • RNA, Messenger / genetics*
  • Tongue Neoplasms / genetics*
  • Transcriptome

Substances

  • Biomarkers, Tumor
  • MicroRNAs
  • RNA, Long Noncoding
  • RNA, Messenger