MicroRNA-132 targets PEA-15 and suppresses the progression of astrocytoma in vitro

J Neurooncol. 2016 Sep;129(2):211-20. doi: 10.1007/s11060-016-2173-2. Epub 2016 Jun 13.

Abstract

Gliomas are highly malignant tumors, the most common of which are astrocytomas. A growing number of studies suggest that dysregulation of miRNAs is a frequent event contributing to the pathogenesis of gliomas. In this study, we found that over-expression of miR-132 inhibited cell proliferation and migration and triggered apoptosis, while knockdown of miR-132 showed opposite effects. PEA-15 was identified as a direct target of miR-132. Reintroduction of PEA-15 without 3'UTR region reversed the inhibitory effects of miR-132 on cell proliferation, migration, and apoptosis. MiR-132 was inversely correlated with the PEA-15 expression. CREB (cAMP response element binding protein) and KLF (Krüppel-like factor 8) were conformed as transcription factors of miR-132, which bidirectionally regulate the expression of miR-132. Our study suggests that miR-132 is an important tumor suppressor of astrocytoma progression by targeting PEA-15, while CREB and KLF can modulate the expression of miR-132, thus providing new insight into the molecular mechanisms underlying astrocytoma progression in vitro.

Keywords: Astrocytoma; CREB; Glioma; KLF; MiR-132; PEA-15.

MeSH terms

  • Analysis of Variance
  • Apoptosis / genetics
  • Apoptosis / physiology
  • Apoptosis Regulatory Proteins
  • Astrocytoma / metabolism*
  • Astrocytoma / pathology
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / pathology
  • CREB-Binding Protein / genetics
  • CREB-Binding Protein / metabolism
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Movement / physiology
  • Cell Proliferation / genetics
  • Cell Proliferation / physiology
  • Disease Progression
  • Gene Expression Regulation, Neoplastic / genetics
  • Gene Expression Regulation, Neoplastic / physiology*
  • Glioma
  • HEK293 Cells
  • Humans
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Kruppel-Like Transcription Factors
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Phosphoproteins / metabolism*
  • RNA, Messenger
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism
  • Sincalide / metabolism
  • Time Factors
  • Transfection

Substances

  • Apoptosis Regulatory Proteins
  • Intracellular Signaling Peptides and Proteins
  • KLF8 protein, human
  • Kruppel-Like Transcription Factors
  • MIRN132 microRNA, human
  • MicroRNAs
  • PEA15 protein, human
  • Phosphoproteins
  • RNA, Messenger
  • Repressor Proteins
  • CREB-Binding Protein
  • Sincalide