miR-720 is a key regulator of glioma migration and invasion by controlling TARSL2 expression

Hum Cell. 2021 Sep;34(5):1504-1516. doi: 10.1007/s13577-021-00551-x. Epub 2021 May 23.

Abstract

Glioblastoma (GBM) is the most lethal type of primary brain tumor and is characterized by diffuse infiltrative growth. However, the mechanisms that control this phenotype remain largely unknown. Emerging evidence has demonstrated that the abnormal expression of microRNAs and their target genes are involved in the migration and invasion of glioma cells. In this study, we demonstrated that microRNA-720 (miR-720) was significantly upregulated in glioma tissues and cells. Functional experiments showed that overexpression of miR-720 promotes glioma migration and invasion, while downregulation of miR-720 inhibits glioma migration and invasion. Meanwhile, we found that threonyl-tRNA synthetase like-2 (TARSL2) was a direct and functional target of miR-720 in glioma. Reintroduction of TARSL2 into glioma cells repressed the invasion promoting function of miR-720, whereas downregulation of TARSL2 reversed the anti-invasion function of anti-miR-720. Furthermore, quantitative real-time polymerase chain reaction results showed that miR-720 was inversely correlated with TARSL2 expression in 40 GBM tissues. Finally, in vivo experiments showed that miR-720 promotes glioma growth and upregulates invasion-related genes in nude mice. Overall, our findings suggest increasing miR-720 enhances glioma migration and invasion through downregulation of TARSL2, which may provide novel insight into the treatment of glioma.

Keywords: Glioma; Invasion; MiR-720; Migration; TARSL2.

MeSH terms

  • Cell Movement / genetics*
  • Gene Expression Regulation, Neoplastic / genetics*
  • Glioma / genetics*
  • Glioma / pathology*
  • Humans
  • MicroRNAs / genetics*
  • MicroRNAs / physiology*
  • Neoplasm Invasiveness / genetics*
  • Threonine-tRNA Ligase / genetics*
  • Threonine-tRNA Ligase / metabolism*
  • Tumor Cells, Cultured

Substances

  • MIRN720 microRNA, human
  • MicroRNAs
  • TARS3 protein, human
  • Threonine-tRNA Ligase