Comprehensive analysis of dysregulated lncRNAs, miRNAs and mRNAs with associated ceRNA network in esophageal squamous cell carcinoma

Gene. 2019 May 15:696:206-218. doi: 10.1016/j.gene.2019.02.051. Epub 2019 Feb 22.

Abstract

Mounting evidence suggests that long noncoding RNAs (lncRNAs) play an important role in tumor biology. To date, some lncRNAs have been found to be involved in competitive binding of miRNAs, a major group of competitive endogenous RNAs (ceRNAs), through participation in a regulatory network of protein-coding gene expression. However, the functional roles of lncRNA-mediated ceRNAs in esophageal squamous cell carcinoma (ESCC) have rarely been reported. Here, we construct a hypothetical ceRNA network by analyzing differential expression of lncRNAs, miRNAs and mRNAs obtained from 96 ESCC tissues and 13 normal tissues in the Cancer Genome Atlas. Ultimately, 95 lncRNAs, 9 miRNAs, and 40 mRNAs were identified (fold change >1.5, P < .05) and included in the ceRNA network for ESCC. Moreover, three lncRNAs (IGF2-AS, MUC2 and SOX2-OT) were found to be significantly associated with overall survival (log-rank test, P < .05), and further experiments revealed that lncRNA DLX6-AS1 knockdown inhibited the proliferation and invasion of esophageal cancer cells by enhancing the endogenous function of mTOR. We believe that the identified ceRNA network can facilitate a better understanding of lncRNA-related mechanisms in ESCC.

Keywords: Competing endogenous RNA; DLX6-AS1; Esophageal squamous cell carcinoma; Long noncoding RNA; The cancer genome atlas.

MeSH terms

  • Cell Line, Tumor
  • Datasets as Topic
  • Esophageal Neoplasms / genetics*
  • Esophageal Neoplasms / mortality
  • Esophageal Neoplasms / pathology
  • Esophageal Squamous Cell Carcinoma / genetics*
  • Esophageal Squamous Cell Carcinoma / mortality
  • Esophageal Squamous Cell Carcinoma / pathology
  • Esophagus / pathology
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Gene Knockdown Techniques
  • Gene Regulatory Networks*
  • HEK293 Cells
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Mucin-2 / genetics
  • Neoplasm Invasiveness / genetics
  • Prognosis
  • Proteins
  • RNA, Antisense / genetics
  • RNA, Antisense / metabolism*
  • RNA, Long Noncoding / metabolism
  • RNA, Messenger / metabolism
  • TOR Serine-Threonine Kinases / genetics

Substances

  • IGF2-AS lncRNA, human
  • MUC2 protein, human
  • Mucin-2
  • Proteins
  • RNA, Antisense
  • RNA, Long Noncoding
  • RNA, Messenger
  • long non-coding RNA Sox2ot, human
  • MTOR protein, human
  • TOR Serine-Threonine Kinases