MicroRNA-379 mediates pigmentation, migration and proliferation of melanocytes by targeting the insulin-like growth factor 1 receptor

Exp Dermatol. 2020 May;29(5):467-476. doi: 10.1111/exd.14095. Epub 2020 Apr 2.

Abstract

Melanogenesis, migration and proliferation of melanocytes are important factors that determine the hair colours of mammals. MicroRNAs (miRNAs) have been shown to be closely related to these processes. In melanocytes of alpacas, insulin-like growth factor 1 (IGF1) has been shown to improve melanogenesis through the cyclic AMP (cAMP) pathway. miR-379 was predicted to target insulin-like growth factor (IGF) receptor 1 (IGF1R), which binds to IGF1. Therefore, we hypothesized that miR-379 could mediate melanogenesis, migration and proliferation of melanocytes. Here, we report that miR-379 was highly expressed in alpaca melanocytes. Subsequent overexpression of miR-379 in alpaca melanocytes led to the generation of the phenotype of melanogenesis, proliferation and migration. In addition, the expression of genes related to these phenotypes in melanocytes was detected. Our results showed that miR-379 targets IGF1R in melanocytes. The overexpression of miR-379 stimulated dendrite extension or elongation and limited the perinuclear distribution of melanin, but inhibited melanogenesis via cAMP response element (CRE)-binding protein (CREB)/microphthalmia-associated transcription factor (MITF) pathway. miR-379 attenuated melanocyte migration by downregulating the focal adhesion kinase (FAK) and enhanced melanocyte proliferation by upregulating protein kinase B (AKT). These observations suggest the involvement of miR-379 in the physiological regulation of melanocytes, mediated by targeting IGF1R on insulin receptor (IR) compensation and subsequent crosstalk.

Keywords: insulin-like growth factor receptor 1; melanocyte; miR-379; migration; pigmentation; proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Activating Transcription Factor 2 / metabolism
  • Animals
  • Camelids, New World / metabolism*
  • Cell Movement
  • Cell Proliferation
  • Melanins / metabolism
  • Melanocytes / metabolism*
  • Mice
  • MicroRNAs / biosynthesis*
  • MicroRNAs / genetics
  • Microphthalmia-Associated Transcription Factor / metabolism
  • Phenotype
  • Pigmentation*
  • Polymerase Chain Reaction
  • Protein Binding
  • Receptor, IGF Type 1 / biosynthesis*
  • Receptor, Insulin / metabolism

Substances

  • 3' Untranslated Regions
  • Activating Transcription Factor 2
  • Atf2 protein, mouse
  • Igf1r protein, mouse
  • MIRN379 microRNA, mouse
  • Melanins
  • MicroRNAs
  • Microphthalmia-Associated Transcription Factor
  • Receptor, IGF Type 1
  • Receptor, Insulin