MiR-26b reverses temozolomide resistance via targeting Wee1 in glioma cells

Cell Cycle. 2017 Oct 18;16(20):1954-1964. doi: 10.1080/15384101.2017.1367071. Epub 2017 Sep 12.

Abstract

Emerging evidence has demonstrated that microRNAs (miRNA) play a critical role in chemotherapy-induced epithelial-mesenchymal transition (EMT) in glioma. However, the underlying mechanism of chemotherapy-triggered EMT has not been fully understood. In the current study, we determined the role of miR-26b in regulation of EMT in stable temozolomide (TMZ)-resistant (TR) glioma cells, which have displayed mesenchymal features. Our results illustrated that miR-26b was significantly downregulated in TR cells. Moreover, ectopic expression of miR-26b by its mimics reversed the phenotype of EMT in TR cells. Furthermore, we found that miR-26b governed TR-mediate EMT partly due to governing its target Wee1. Notably, overexpression of miR-26b sensitized TR cells to TMZ. These findings suggest that upregulation of miR-26b or targeting Wee1 could serve as novel approaches to reverse chemotherapy resistance in glioma.

Keywords: Glioma; Wee1; growth; miR-26b; temozolomide.

MeSH terms

  • Base Sequence
  • Biomarkers, Tumor / metabolism
  • Cell Cycle Proteins / metabolism*
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Dacarbazine / analogs & derivatives*
  • Dacarbazine / pharmacology
  • Dacarbazine / therapeutic use
  • Down-Regulation / genetics
  • Drug Resistance, Neoplasm / drug effects
  • Drug Resistance, Neoplasm / genetics*
  • Epithelial-Mesenchymal Transition / genetics
  • Glioma / drug therapy*
  • Glioma / genetics*
  • Glioma / pathology
  • Humans
  • MicroRNAs / metabolism*
  • Neoplasm Invasiveness
  • Nuclear Proteins / metabolism*
  • Phenotype
  • Protein-Tyrosine Kinases / metabolism*
  • Temozolomide

Substances

  • Biomarkers, Tumor
  • Cell Cycle Proteins
  • MIRN26A microRNA, human
  • MicroRNAs
  • Nuclear Proteins
  • Dacarbazine
  • Protein-Tyrosine Kinases
  • WEE1 protein, human
  • Temozolomide