MicroRNA‑138 modulates glioma cell growth, apoptosis and invasion through the suppression of the AKT/mTOR signalling pathway by targeting CREB1

Oncol Rep. 2020 Dec;44(6):2559-2568. doi: 10.3892/or.2020.7809. Epub 2020 Oct 15.

Abstract

Alterations in the expression of microRNA (miR)‑138 have been demonstrated to result in the development of several malignant tumours. However, the possible function of miR‑138 in human glioma cells remains unclear. The present study demonstrated that miR‑138 was significantly downregulated in 48 human glioma specimens by quantitative PCR analysis. The upregulation of miR‑138 exerted significant antiproliferative and anti‑invasive effects on glioma cells and promoted their apoptosis. In addition, cAMP response element‑binding protein 1 (CREB1) was confirmed as a direct target gene of miR‑138 by luciferase gene reporter assay, and the antitumour effect of miR‑138 on glioma cells was significantly reversed by CREB1 overexpression. Moreover, the molecular mechanisms underlying the tumour‑suppressive role of miR‑138 in malignant glioma may be associated with the dephosphorylation of AKT/mTOR caused by the miR‑138 upregulation‑induced decrease in CREB1 expression in glioma cells. The results of the present study indicated that miR‑138 may affect CREB1/AKT/mTOR signalling to regulate the proliferation, apoptosis and invasion of glioma cells and the malignant progression of glioma, thereby suggesting that miR‑138 may be a potential target for the treatment of gliomas.

Keywords: microRNA-138; glioma; cAMP response elementbinding protein 1; apoptosis; proliferation; invasion.

Publication types

  • Observational Study

MeSH terms

  • Apoptosis / genetics
  • Brain / pathology
  • Brain / surgery
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / mortality
  • Brain Neoplasms / pathology
  • Brain Neoplasms / surgery
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Cyclic AMP Response Element-Binding Protein / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Glioma / genetics*
  • Glioma / mortality
  • Glioma / pathology
  • Glioma / surgery
  • HEK293 Cells
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • MicroRNAs / metabolism*
  • Middle Aged
  • Neoplasm Invasiveness / genetics
  • Signal Transduction / genetics
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • CREB1 protein, human
  • Cyclic AMP Response Element-Binding Protein
  • MIRN138 microRNA, human
  • MicroRNAs
  • MTOR protein, human
  • TOR Serine-Threonine Kinases