iASPP, a microRNA‑124 target, is aberrantly expressed in astrocytoma and regulates malignant glioma cell migration and viability

Mol Med Rep. 2018 Jan;17(1):1970-1978. doi: 10.3892/mmr.2017.8097. Epub 2017 Nov 15.

Abstract

MicroRNAs (miRNAs) regulate biogenesis and disease development by targeting numerous mRNAs. miRNA (miR)‑124 and its direct target, inhibitor of apoptosis‑stimulating protein of p53 (iASPP), may be involved in tumor development and progression. The aim of the present study was to explore the role of miR‑124‑targeted iASPP in glioma. The results demonstrated that miR‑124 was aberrantly expressed in astrocytic glioma tissue and in the human glioblastoma cell lines U87 and U251. The expression of miR‑124 was lower in astrocytic gliomas compared with normal brain (NB) tissues, with a more reduced expression in higher‑grade tumors. In addition, several miR‑124 loci (including miR‑124‑1, miR‑124‑2 and miR‑124‑3) were revealed to be more highly methylated in U87 cells compared with methylation levels in U251 cells and NB cells. Furthermore, the expression of iASPP was higher in high‑grade astrocytic gliomas compared with low‑grade astrocytic gliomas. miR‑124 overexpression effectively inhibited U87 and U251 cell migration. In addition, miR‑124 regulated cell viability and arrested the cell cycle at the G0/G1 phase in these two cell lines. miR‑124 also reduced the expression levels of the cell cycle related genes iASPP, cyclin‑dependent kinase (CDK)4, CDK6 and cyclin D1. Results from the present study indicated that expression of the miR‑124 target gene iASPP may contribute to glioma development and progression.

MeSH terms

  • Astrocytoma / genetics*
  • Astrocytoma / pathology
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Cell Survival
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Glioblastoma / genetics
  • Glioblastoma / pathology
  • Glioma / genetics*
  • Glioma / pathology
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • Repressor Proteins / genetics*

Substances

  • Intracellular Signaling Peptides and Proteins
  • MIRN124 microRNA, human
  • MicroRNAs
  • PPP1R13L protein, human
  • Repressor Proteins