Isorhapontigenin (ISO) inhibits EMT through FOXO3A/METTL14/VIMENTIN pathway in bladder cancer cells

Cancer Lett. 2021 Nov 1:520:400-408. doi: 10.1016/j.canlet.2021.07.041. Epub 2021 Jul 28.

Abstract

Epithelial mesenchymal transition (EMT) is highly correlated with metastasis during cancer development. Although previous studies have revealed that ISO is able to inhibit cancer cell invasion and stem-cell properties, little is known about the effects of ISO on EMT markers. The present study explores the potential regulation of ISO on EMT, leading to the inhibition of migration and invasion of bladder cancer cells. We found that ISO inhibited Vimentin, one of the EMT markers, in the invasive bladder cancer cell lines U5637 and T24T. ISO reduced Vimentin protein level by increasing the expression of METTL14. On the other hand, ISO upregulated the METTL14 mRNA by activating the transcription factor FOXO3a. The results demonstrate that ISO inhibits invasion by affecting the EMT marker and offer a novel insight into understanding the upregulation of METTL14 by ISO.

Keywords: EMT; FOXO3a; ISO; METTL14; Vimentin.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Epithelial-Mesenchymal Transition / drug effects
  • Forkhead Box Protein O3 / genetics*
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Methyltransferases / genetics*
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology
  • Signal Transduction / drug effects
  • Stilbenes / pharmacology
  • Urinary Bladder Neoplasms / drug therapy*
  • Urinary Bladder Neoplasms / genetics
  • Urinary Bladder Neoplasms / pathology
  • Vimentin / antagonists & inhibitors
  • Vimentin / genetics*

Substances

  • FOXO3 protein, human
  • Forkhead Box Protein O3
  • Stilbenes
  • VIM protein, human
  • Vimentin
  • isorhapontigenin
  • METTL14 protein, human
  • Methyltransferases