miR-137 inhibits melanoma cell proliferation through downregulation of GLO1

Sci China Life Sci. 2018 May;61(5):541-549. doi: 10.1007/s11427-017-9138-9. Epub 2018 Jan 2.

Abstract

Late-stage melanoma is refractory to current therapies. MicroRNAs (miRNAs) can modulate many physiological and pathological processes of melanoma. Studies have demonstrated that miR-137 acts as a tumor suppressor by inhibiting the proliferation of melanoma cells through targeting multiple mRNAs. The glyoxalase system member glyoxalase 1 (GLO1) is the principal scavenging enzyme of methylglyoxal (MG), a toxic byproduct of glycolysis. Using 35S in vivo/vitro labelling analysis for dynamic proteomics (SiLAD), we found that miR-137 downregulated the expression of GLO1 in melanoma cells. Bioinformatics analysis predicted that GLO1 is a direct target of miR-137. This was validated by dual luciferase reporter assay. Quantitative RT-PCR (qRT-PCR) and western blot analysis indicated that miR-137 could decrease endogenous GLO1 expression. Furthermore, siRNA targeting of GLO1 mimicked inhibition of melanoma cell proliferation caused by miR-137 overexpression. Re-expression of GLO1 was able to restore miR-137-mediated suppression of melanoma cell proliferation. Therefore, these results suggest that miR-137 inhibits the proliferation of melanoma cells by targeting GLO1.

Keywords: GLO1; SiLAD; cell proliferation; melanoma; miR-137.

MeSH terms

  • 3' Untranslated Regions
  • Cell Line, Tumor
  • Cell Proliferation / physiology
  • Gene Expression Regulation, Neoplastic / genetics*
  • Gene Knockdown Techniques
  • Humans
  • Lactoylglutathione Lyase / genetics*
  • Melanoma / metabolism*
  • Melanoma / pathology*
  • MicroRNAs / metabolism*

Substances

  • 3' Untranslated Regions
  • MIRN137 microRNA, human
  • MicroRNAs
  • GLO1 protein, human
  • Lactoylglutathione Lyase