Participation of tumor suppressors long non-coding RNA MEG3, microRNA-377 and PTEN in glioma cell invasion and migration

Pathol Res Pract. 2019 Oct;215(10):152558. doi: 10.1016/j.prp.2019.152558. Epub 2019 Jul 23.

Abstract

Purpose: Glioma is a common and fatal intracranial tumor. Both miR-377 and lncRNA MEG3 are tumor suppressors. This study was performed to investigate the association between miR-377 and lncRNA MEG3 in glioma cells.

Methods: U118 and U251 cell lines were incubated in Dulbecco's modified Eagle's medium supplemented with miR-377 mimics, MEG3 siRNA (si-MEG3) and/or MEG3 overexpression plasmids (pc-MEG3) for 48 h. Cell migration, invasion, apoptosis, cell cycle distribution and the expression of E26 tansformation-specific-1 (ETS-1), phosphatase and tensin homologue (PTEN), E-cadherin, N-cadherin and β-catenin were detected.

Results: MiR-377 mimics increased MEG3 expression and decreased the number of migrated and invaded U118 and U251 cells, without influence on apoptosis in both cell lines. Si-MEG3 transfection increased U118 cell migration and invasion and rescued miR-377 mimics-induced inhibitory in cell migration and invasion. Si-MEG3 decreased U118 cell apoptosis and induced G0/G1 cell cycle arrest, and pc-MEG3 increased U251 cell apoptosis via arresting cell cycle at G2/M phage. MiR-377 mimics and si-MEG3 increased the relative expression level of N-cadherin mRNA, and both si-MEG3 and pc-MEG3 increased E-cadherin in glioma cells. MiR-377 mimics increased ETS-1 mRNA in U118 cells, but decreased it in U251 cells. PTEN was increased by miR-377 mimics and si-MEG3 and decreased by pc-MEG3 in glioma cells.

Conclusions: These results suggested the link interaction of MEG3 with miR-377 and PTEN, but not functioning as the competing endogenous RNA. MiR-377 mimics and MEG3 were tumor suppressors in glioma cells through regulating PTEN expression.

Keywords: Glioma; Invasion; Migration; lncRNA MEG3; microRNA-377.

MeSH terms

  • Apoptosis / genetics
  • Brain Neoplasms / genetics
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / pathology
  • Cell Cycle Checkpoints / genetics
  • Cell Line, Tumor
  • Cell Movement / genetics*
  • Cell Proliferation / genetics
  • Gene Expression Regulation, Neoplastic
  • Glioma / genetics
  • Glioma / metabolism*
  • Glioma / pathology
  • Humans
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neoplasm Invasiveness / genetics*
  • Neoplasm Invasiveness / pathology
  • PTEN Phosphohydrolase / genetics
  • PTEN Phosphohydrolase / metabolism*
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • RNA, Small Interfering

Substances

  • MEG3 non-coding RNA, human
  • MIRN377 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • RNA, Small Interfering
  • PTEN Phosphohydrolase