MicroRNA-361-5p inhibits epithelial-to-mesenchymal transition of glioma cells through targeting Twist1

Oncol Rep. 2017 Mar;37(3):1849-1856. doi: 10.3892/or.2017.5406. Epub 2017 Jan 25.

Abstract

MicroRNA-361-5p (miR-361-5p) has been reported to be dysregulated in various human cancer types. However, the function of miR-361-5p in glioma remains unknown. In the present study, we aimed to investigate the biological functions of miR-361-5p in regulating glioma progression and the underlying molecular mechanism. We found that miR-361-5p was significantly decreased in glioma tissues and cell lines as detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis. Functional analysis revealed that miR-361-5p overexpression significantly inhibited glioma cell migration, invasion and epithelial-mesenchymal transition (EMT) whereas suppression of miR-361-5p showed opposite effects. Bioinformatic analysis showed that Twist1, a critical EMT inducer, was a predicted target of miR-361-5p which was validated by dual-luciferase reporter assay, RT-qPCR and western blot analysis. Further analysis indicated that miR-361-5p regulates the Twist1/Bmi-1 signaling axis. Rescue experiments showed that restoration of Twist1 expression significantly reversed the suppressive effect of miR-361-5p on cell migration, invasion and EMT. Taken together, the present study demonstrated an important role of miR-361-5p in glioma - which regulated the EMT of glioma cells by targeting and regulating Twist1. These findings provide novel insight into understanding the role and mechanism of miR-361-5p in regulating the biolo-gical behavior of glioma cells and suggest that miR-361-5p is a novel potential therapeutic target for glioma.

MeSH terms

  • Blotting, Western
  • Cell Movement
  • Epithelial-Mesenchymal Transition*
  • Gene Expression Regulation, Neoplastic*
  • Glioma / genetics
  • Glioma / metabolism
  • Glioma / pathology*
  • Humans
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness
  • Nuclear Proteins / antagonists & inhibitors
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction
  • Tumor Cells, Cultured
  • Twist-Related Protein 1 / antagonists & inhibitors
  • Twist-Related Protein 1 / genetics
  • Twist-Related Protein 1 / metabolism*

Substances

  • MIRN361 microRNA, human
  • MicroRNAs
  • Nuclear Proteins
  • RNA, Messenger
  • TWIST1 protein, human
  • Twist-Related Protein 1