Exogenous expression of miRNA-3613-3p causes APAF1 downregulation and affects several proteins involved in apoptosis in BE(2)-C human neuroblastoma cells

Int J Oncol. 2018 Oct;53(4):1787-1799. doi: 10.3892/ijo.2018.4509. Epub 2018 Jul 31.

Abstract

MicroRNAs (miRNAs) are a class of small non‑coding RNAs involved in post‑transcriptional gene regulation. Furthermore, dysregulation of miRNA expression is an important factor in the pathogenesis of neuroblastoma. Our previous study identified that overexpression of monocyte chemoattractant protein‑induced protein 1 protein led to a significant downregulation of a novel miRNA molecule, miRNA‑3613‑3p. In the present study, the potential involvement of miRNA‑3613‑3p in the cell biology of neuroblastoma was investigated. It was identified that the expression of miRNA‑3613‑3p varies among a range of human neuroblastoma cell lines. As the delineation of the functions of a miRNA requires the identification of its target genes, seven putative mRNAs that may be regulated by miRNA‑3613‑3p were selected. Furthermore, it was identified that overexpression of miRNA‑3613‑3p causes significant downregulation of several genes exhibiting tumor suppressive potential [encoding apoptotic protease‑activating factor 1 (APAF1), Dicer, DNA fragmentation factor subunit β, von Hippel‑Lindau protein and neurofibromin 1] in BE(2)‑C human neuroblastoma cells. APAF1 mRNA was the most significantly decreased transcript in the cells with miRNA‑3613‑3p overexpression. In accordance with the aforementioned results, the downregulation of cleaved caspase-9 and lack of activation of executive caspases in BE(2)‑C cells following miRNA‑3613‑3p overexpression was observed. The results of the present study suggest a potential underlying molecular mechanism of apoptosis inhibition via APAF1 downregulation in human neuroblastoma BE(2)‑C cells with miRNA‑3613‑3p overexpression.

MeSH terms

  • 3' Untranslated Regions / genetics
  • Apoptosis / genetics*
  • Apoptotic Protease-Activating Factor 1 / genetics*
  • Apoptotic Protease-Activating Factor 1 / metabolism
  • Cell Line, Tumor
  • Down-Regulation
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neuroblastoma / genetics*
  • RNA, Messenger / genetics

Substances

  • 3' Untranslated Regions
  • APAF1 protein, human
  • Apoptotic Protease-Activating Factor 1
  • MIRN3613 microRNA, human
  • MicroRNAs
  • RNA, Messenger