Comprehensive analysis of differentially expressed profiles of lncRNAs, mRNAs, and miRNAs in laryngeal squamous cell carcinoma in order to construct a ceRNA network and identify potential biomarkers

J Cell Biochem. 2019 Oct;120(10):17963-17974. doi: 10.1002/jcb.29063. Epub 2019 May 24.

Abstract

Objective: This study aimed to uncover a regulatory network comprised of long noncoding RNAs (lncRNAs), microRNAs (miRNAs), and messenger RNAs (mRNAs) in laryngeal squamous cell carcinoma (LSCC), to explore its underlying mechanisms and development, and to identify key genetic biomarkers for the prognosis of LSCC.

Methods: Here, we compared mRNA, lncRNA, and miRNA expression profiles between 111 LSCC and 12 adjacent normal tissues using RNA sequencing (RNA-Seq) data from the Cancer Genome Atlas (TCGA) database. Based on the interaction information obtained from miRcode, TargetScan, miRTarBase, and miRDB, a lncRNA-miRNA-mRNA competing endogenous RNA (ceRNA) network was constructed using differentially expressed lncRNAs (DElncRNA), miRNAs (DEmiRNA), and mRNAs (DEmRNA). By assessing the functional enrichment of DEmRNAs in this network, the potential underlying mechanisms were explored. In addition, Kaplan-Meier survival analysis was used to assess genetic biomarkers related to the prognosis of LSCC patients.

Results: Upon comparing LSCC and control tissues, 1640 DElncRNAs, 75 DEmiRNAs, and 3217 DEmRNAs were identified. Based on the prediction between lncRNA-miRNA and miRNA-mRNA relationships, we constructed a ceRNA network comprised of 93 lncRNAs, nine miRNAs, and nine mRNAs. This network predicted that two lncRNAs (AC016773.1 and C00299), two mRNAs (DIO1 and STC2), and two miRNAs (hsa-mir-137 and hsa-mir-210) were significant biomarkers of LSCC prognosis according to thorough topological and survival analyses (P < .05).

Conclusion: Through a ceRNA network analysis, our study identifies new lncRNAs, miRNAs, and mRNAs, which can be used as potential biomarkers of LSCC and as therapeutic targets for treating LSCC, thus laying a foundation for future clinical studies.

Keywords: LSCC; biomarkers; ceRNA network; expression profiles; overall survival.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Squamous Cell / genetics*
  • Gene Expression Profiling*
  • Gene Expression Regulation, Neoplastic
  • Gene Ontology
  • Gene Regulatory Networks*
  • Humans
  • Kaplan-Meier Estimate
  • Laryngeal Neoplasms / genetics*
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Molecular Sequence Annotation
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / metabolism
  • RNA, Messenger / genetics*

Substances

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