Analysis of microRNA-203 function in CREB/MITF/RAB27a pathway: comparison between canine and human melanoma cells

Vet Comp Oncol. 2016 Dec;14(4):384-394. doi: 10.1111/vco.12118. Epub 2014 Oct 3.

Abstract

MicroRNA (miR)-203 is downregulated and acts as an anti-oncomir in melanoma cells. Here, using human and canine melanoma cells, we elucidated the effects of miR-203 on cyclic adenosine monophosphate response element binding protein (CREB)/microphthalmia-associated transcription factor (MITF)/RAB27a pathway, which is known to be important for the development and progression of human melanoma. In this study, we showed that miR-203 directly targeted CREB1 and regulated its downstream targets, MITF and RAB27a. miR-203 significantly suppressed the growth of human and canine melanoma cells and inhibited melanosome transport through the suppression of the signalling pathway. In conclusion, miR-203 was shown to be a common tumour-suppressive miRNA in human and canine melanoma and thus to play a crucial role in the biological mechanisms of melanoma development.

Keywords: CREB/MITF/RAB27a pathway; cell signalling; comparative oncology; melanoma; microRNA-203.

MeSH terms

  • Animals
  • Cyclic AMP Response Element-Binding Protein / genetics
  • Cyclic AMP Response Element-Binding Protein / metabolism*
  • Dog Diseases / metabolism*
  • Dogs
  • Gene Expression Regulation, Neoplastic / physiology*
  • Humans
  • Melanoma / metabolism
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Microphthalmia-Associated Transcription Factor / genetics
  • Microphthalmia-Associated Transcription Factor / metabolism*
  • Species Specificity
  • rab GTP-Binding Proteins / genetics
  • rab GTP-Binding Proteins / metabolism*
  • rab27 GTP-Binding Proteins

Substances

  • Cyclic AMP Response Element-Binding Protein
  • MIRN203 microRNA, human
  • MicroRNAs
  • Microphthalmia-Associated Transcription Factor
  • rab27 GTP-Binding Proteins
  • RAB27A protein, human
  • rab GTP-Binding Proteins