Long non-coding RNA AC023115.3 suppresses chemoresistance of glioblastoma by reducing autophagy

Biochim Biophys Acta Mol Cell Res. 2017 Aug;1864(8):1393-1404. doi: 10.1016/j.bbamcr.2017.05.008. Epub 2017 May 9.

Abstract

Malignant glioma is an aggressive brain cancer that responds poorly to chemotherapy. However, the molecular mechanism underlying the development of chemoresistance in glioma is not well-understood. In this study, we show that long non-coding RNA AC023115.3 is induced by cisplatin in human glioblastoma cells and that elevated AC023115.3 promotes cisplatin-induced apoptosis by inhibiting autophagy. Further mechanistic studies revealed that AC023115.3 acts as a competing endogenous RNA for miR-26a and attenuates the inhibitory effect of miR-26a on GSK3β, a proline-directed serine-threonine kinase that promotes the degradation of Mcl1, leading to an increase in GSK3β and a decrease in autophagy. Additionally, we discovered that AC023115.3 improves chemosensitivity of glioma cells to cisplatin by regulating the miR-26a-GSK3β-Mcl1 pathway. Thus, these data indicate that the AC023115.3-miR-26a-GSK3β signalling axis plays an important role in reducing the chemoresistance of glioma.

Keywords: Autophagy; Chemoresistance; Glioblastoma; Long non-coding RNA; Mcl1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Autophagy / drug effects
  • Autophagy / genetics
  • Binding, Competitive
  • Cell Line, Tumor
  • Cisplatin / pharmacology
  • Drug Resistance, Neoplasm / drug effects*
  • Drug Resistance, Neoplasm / genetics
  • Gene Expression Regulation, Neoplastic*
  • Glycogen Synthase Kinase 3 beta / genetics*
  • Glycogen Synthase Kinase 3 beta / metabolism
  • Humans
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Myeloid Cell Leukemia Sequence 1 Protein / genetics
  • Myeloid Cell Leukemia Sequence 1 Protein / metabolism
  • Neuroglia / drug effects*
  • Neuroglia / metabolism
  • Neuroglia / pathology
  • Proteolysis
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / metabolism
  • Signal Transduction

Substances

  • Antineoplastic Agents
  • MCL1 protein, human
  • MIRN26A microRNA, human
  • MicroRNAs
  • Myeloid Cell Leukemia Sequence 1 Protein
  • RNA, Long Noncoding
  • Glycogen Synthase Kinase 3 beta
  • Cisplatin