Retinoic Acid Induces Differentiation of Mouse F9 Embryonic Carcinoma Cell by Modulating the miR-485 Targeting of Abhd2

Int J Mol Sci. 2019 Apr 26;20(9):2071. doi: 10.3390/ijms20092071.


Retinoic acid (RA) plays a key role in pluripotent cell differentiation. In F9 embryonic carcinoma cells, RA can induce differentiation towards somatic lineages via the Ras-extracellular signal-regulated kinase (Ras/Erk) pathway, but the mechanism through which it induces the Erk1/2 phosphorylation is unclear. Here, we show that miR-485 is a positive regulator that targets α/β-hydrolase domain-containing protein 2 (Abhd2), which can result in Erk1/2 phosphorylation and triggers differentiation. RA up-regulates miR-485 and concurrently down-regulates Abhd2. We verified that Abhd2 is targeted by miR-485 and they both can influence the phosphorylation of Erk1/2. In summary, RA can mediate cell differentiation by phosphorylating Erk1/2 via miR-485 and Abhd2.

Keywords: Abhd2; Erk1/2; differentiation; miR-485; retinoic acid.

MeSH terms

  • Animals
  • Biomarkers
  • Cell Differentiation / drug effects*
  • Cell Differentiation / genetics*
  • Embryonal Carcinoma Stem Cells
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Humans
  • Hydrolases / genetics*
  • MAP Kinase Signaling System / drug effects
  • Mice
  • MicroRNAs / genetics*
  • Phosphorylation
  • RNA Interference*
  • Tretinoin / pharmacology*


  • Biomarkers
  • MicroRNAs
  • Tretinoin
  • Hydrolases
  • Abhd2 protein, mouse