miR-143 inhibits oncogenic traits by degrading NUAK2 in glioblastoma

Int J Mol Med. 2016 Jun;37(6):1627-35. doi: 10.3892/ijmm.2016.2562. Epub 2016 Apr 13.

Abstract

Despite evidence that the crucial role of NUAK family, SNF1-like kinase, 2 [NUAK2; also known as sucrose non-fermenting 1 (SNF1)-like kinase (SNARK)], has been highlighted in cancer development and in tumor progression, to the best of our knowledge, there are no studies available to date on the role of NUAK2 in glioblastoma. Thus, in this study, in order to determine the role of NUAK2 in glioblastoma, we performed western blot analysis to detect its expression in glioma. The results demonstrated that NUAK2 expression was upregulated in glioma tissues and that its expression was associated with the advanced stages of the disease. In vitro, NUAK2 overexpression promoted the proliferation, migration and invasion of A172 glioblastoma cells, whereas the silencing of NUAK2 with a plasmid carrying shRNA targeting NUAK2 inhibited the proliferation of A172 glioblastoma cells. Moreover, NUAK2 regulated cancer stem cell (CSC)-related gene expression in the glioblastoma cells. We performed an analysis of potential microRNA (miR or miRNA) target sites using 3 commonly used prediction algorithms, miRanda, TargetScan and PicTar. All 3 algorithms predicted that miR‑143 targeted the 3'-untranslated region (3'UTR) of NUAK2. Subsequent experiments confirmed this prediction. Finally, we found that miR‑143 inhibited the proliferation, migration and invasion of the glioblastoma cells. Thus, the findings of the present study demonstrate that miR‑143 inhibits oncogenic traits by degrading NUAK2 in glioblastoma.

MeSH terms

  • 3' Untranslated Regions
  • Adult
  • Aged
  • Algorithms
  • Base Sequence
  • Binding Sites
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Glioblastoma / genetics*
  • Glioblastoma / metabolism
  • Glioblastoma / pathology
  • Humans
  • Male
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Middle Aged
  • Neoplastic Stem Cells / metabolism*
  • Neoplastic Stem Cells / pathology
  • Protein Serine-Threonine Kinases / antagonists & inhibitors
  • Protein Serine-Threonine Kinases / genetics*
  • Protein Serine-Threonine Kinases / metabolism
  • Proteolysis
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Signal Transduction

Substances

  • 3' Untranslated Regions
  • MIRN143 microRNA, human
  • MicroRNAs
  • RNA, Small Interfering
  • NUAK2 protein, human
  • Protein Serine-Threonine Kinases