Resveratrol-induced apoptosis is associated with regulating the miR-492/CD147 pathway in malignant melanoma cells

Naunyn Schmiedebergs Arch Pharmacol. 2021 Apr;394(4):797-807. doi: 10.1007/s00210-020-01981-4. Epub 2020 Oct 3.

Abstract

Resveratrol (RES) as a natural phytoalexin has anti-tumor effects on various cancers through its pro-apoptotic activities. Our aim was to determine that RES induces apoptosis in melanoma cells by regulating miR-492 resulting in decreased CD147 expression. We treated A375 and SK-MEL-28 melanoma cells via RES at different concentrations and time-points. The results have shown that the inhibition rate of A375 and SK-MEL-28 was significantly increased after RES treatment. Subsequently, we investigated cell apoptosis by flow cytometry, as well as detected apoptotic-associated proteins including PARP, Caspase-3, Bcl-2, and Bax by western blotting. Meanwhile, the expression of miR-492 and CD147 was analyzed. We found that RES remarkably induces apoptosis in melanoma cells, along with an upregulation of miR-492 and the inhibition of CD147 expression. Furthermore, the detection of luciferase reporter activity confirmed that miR-492 could target CD147 mRNA, and transfected with mimic miR-492 in cells reduced CD147 expression. We also performed the rescued experiment by using a miR-492 inhibitor in melanoma cells. The results showed that the ability of induced apoptosis by RES in melanoma cells was to be attenuated via inhibiting miR-492 expression resulting in CD147 augment. Finally, we determined that the effect of RES-induced apoptosis in melanoma cells is associated with, at least in part, its ability to regulate the miR-492/CD147 pathway.

Keywords: Apoptosis; CD147; Melanoma; Resveratrol; miR-492.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Apoptosis Regulatory Proteins / metabolism
  • Basigin / antagonists & inhibitors
  • Basigin / genetics
  • Basigin / metabolism
  • Cell Line, Tumor
  • Humans
  • Melanoma / drug therapy*
  • Melanoma / genetics
  • Melanoma / metabolism
  • MicroRNAs / antagonists & inhibitors
  • Poly(ADP-ribose) Polymerases / metabolism
  • Resveratrol / pharmacology*
  • Signal Transduction / drug effects
  • Up-Regulation

Substances

  • Antineoplastic Agents
  • Apoptosis Regulatory Proteins
  • BSG protein, human
  • MIRN492 microRNA, human
  • MicroRNAs
  • Basigin
  • Poly(ADP-ribose) Polymerases
  • Resveratrol