The miR-290-295 cluster suppresses autophagic cell death of melanoma cells

Sci Rep. 2012;2:808. doi: 10.1038/srep00808. Epub 2012 Nov 13.

Abstract

We compared the expression levels of 307 miRNAs in six different B16F1 melanoma cell lines of differing malignant properties and found that the miR-290-295 cluster showed a strong upregulation in the more malignant B16F1 daughter cell lines. Its overexpression in B16F1 cells had no major effects on cell proliferation, migration or anchorage-independent growth, but conferred resistance to glucose starvation. This was mediated by miR-290-295-induced downregulation of several essential autophagy genes, including Atg7 and ULK1, which resulted in inhibition of autophagic cell death induced by glucose starvation. Similar effects were observed after knockdown of Atg7 or ULK1 in B16F1 melanoma cells, and after treatment with two chemical inhibitors of autophagy. Together, these results indicate that autophagy mediates cell death of melanoma cells under chronic nutrient deprivation, and they reveal an unanticipated role of the miR-290-295 cluster in conferring a survival advantage to melanoma cells by inhibiting autophagic cell death.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Animals
  • Autophagy*
  • Autophagy-Related Protein 7
  • Autophagy-Related Protein-1 Homolog
  • Cell Line, Tumor
  • Down-Regulation / drug effects
  • Leucine / analogs & derivatives
  • Leucine / pharmacology
  • Melanoma / metabolism
  • Mice
  • MicroRNAs / metabolism*
  • Microtubule-Associated Proteins / antagonists & inhibitors
  • Microtubule-Associated Proteins / metabolism
  • Multigene Family
  • Pepstatins / pharmacology
  • Protein-Serine-Threonine Kinases / antagonists & inhibitors
  • Protein-Serine-Threonine Kinases / metabolism
  • Sirolimus / pharmacology
  • Starvation

Substances

  • 3' Untranslated Regions
  • Atg7 protein, mouse
  • MicroRNAs
  • Microtubule-Associated Proteins
  • Pepstatins
  • Autophagy-Related Protein-1 Homolog
  • Protein-Serine-Threonine Kinases
  • Ulk1 protein, mouse
  • Autophagy-Related Protein 7
  • Leucine
  • aloxistatin
  • pepstatin
  • Sirolimus