RNA sequencing of exosomes revealed differentially expressed long noncoding RNAs in early-stage esophageal squamous cell carcinoma and benign esophagitis

Epigenomics. 2020 Mar;12(6):525-541. doi: 10.2217/epi-2019-0371. Epub 2020 Feb 11.

Abstract

Aim: To explore the roles of exosomal long noncoding RNAs (lncRNAs) in early-stage esophageal squamous cell carcinoma (ESCC) and benign esophagitis. Materials & methods: Exosomal lncRNAs were analyzed using RNA-seq and validated by quantitative real-time PCR, loss-of-function, co-culture and RNA pulldown assays. Results: Exosomal lncRNAs displayed tighter tissue-specificity, higher expression level and lower splicing efficiency than that of mRNAs. A total of 152 exosomal lncRNAs were differentially expressed between ESCC and controls. A total of 124 exosomal lncRNAs were dysregulated between ESCC and esophagitis. Knockdown of 13 ESCC-associated lncRNAs modified proliferation, migration, and apoptosis of ESCC cells. A novel lncRNA RP5-1092A11.2 was highly expressed in ESCC-derived exosomes, ESCC cells and tumor tissues. Exosomes released from RP5-1092A11.2-knockdown cells inhibited ESCC cell proliferation. Conclusion: Dysregulated exosomal lncRNAs were functionally associated with different disease status in esophagus.

Keywords: RP5-1092A11.2; benign esophagitis; early-stage esophageal squamous cell carcinoma; exosomal lncRNAs; functional assay.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Cell Movement
  • Cell Proliferation
  • Esophageal Neoplasms / genetics*
  • Esophageal Neoplasms / metabolism
  • Esophageal Neoplasms / pathology
  • Esophageal Squamous Cell Carcinoma / genetics*
  • Esophageal Squamous Cell Carcinoma / metabolism
  • Esophageal Squamous Cell Carcinoma / pathology
  • Esophagitis / genetics*
  • Exosomes / genetics*
  • Exosomes / ultrastructure
  • Humans
  • Neoplasm Proteins / metabolism
  • RNA, Long Noncoding / metabolism*
  • RNA, Messenger / metabolism
  • RNA-Seq

Substances

  • Neoplasm Proteins
  • RNA, Long Noncoding
  • RNA, Messenger