Exosomal lncRNA‑ATB activates astrocytes that promote glioma cell invasion

Int J Oncol. 2019 Feb;54(2):713-721. doi: 10.3892/ijo.2018.4644. Epub 2018 Nov 23.

Abstract

Glioma invasion is a main cause of a poor prognosis and relapse in patients suffering from the disease. However, the molecular mechanisms responsible for glioma cell invasion remain poorly understood. In this study, the characteristics of exosomes were identified using electron microscope (TEM), and western blot analysis. The potential mechanism of long non‑coding RNA (lncRNA) activated by TGF‑β (lncRNA‑ATB) was demonstrated using luciferase reporter assays and RNA immunoprecipitation. We found that glioma cell‑derived exosomes promoted the activation of astrocytes and had the ability to shuttle long non‑coding RNA (lncRNA) activated by TGF‑β (lncRNA‑ATB) to astrocytes. More importantly, lncRNA‑ATB activated astrocytes through the suppression of microRNA (miRNA or miR)‑204‑3p in an Argonaute 2 (Ago2)‑dependent manner. Furthermore, astrocytes activated by lncRNA‑ATB in turn promoted the migration and invasion of glioma cells. Taken together, the findings of this study suggest that lncRNA‑ATB may play an important role in modulating glioma microenvironment through exosomes. Thus, a better understanding of this process may provide implications for the prevention of highly invasive glioma.

Keywords: glioma; astrocytes; long non coding RNA ATB; microRNA-204-3p.

MeSH terms

  • Astrocytes / metabolism
  • Astrocytes / pathology
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Exosomes / genetics*
  • Gene Expression Regulation, Neoplastic
  • Glioma / genetics*
  • Glioma / pathology
  • Humans
  • MicroRNAs / genetics
  • Microscopy, Electron
  • Neoplasm Invasiveness / genetics
  • Neoplasm Recurrence, Local / genetics
  • Neoplasm Recurrence, Local / pathology
  • RNA, Long Noncoding / genetics*
  • Transforming Growth Factor beta / genetics*
  • Tumor Microenvironment / genetics

Substances

  • MicroRNAs
  • RNA, Long Noncoding
  • Transforming Growth Factor beta