A loop involving NRF2, miR-29b-1-5p and AKT, regulates cell fate of MDA-MB-231 triple-negative breast cancer cells

Anna De Blasio, Riccardo Di Fiore, Giovanni Pratelli, Riccardo Di Fiore, Christian Saliba, Shawn Baldacchino, Renza Vento, Giovanni Tesoriere, Christian Scerri, Godfrey Grech, Rosa Drago Ferrante

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)

Abstract

The present study shows that nuclear factor erythroid 2-related factor 2 (NRF2) and miR-29b-1-5p are two opposite forces which could regulate the fate of MDA-MB-231 cells, the most studied triple-negative breast cancer (TNBC) cell line. We show that NRF2 activation stimulates cell growth and markedly reduces reactive oxygen species (ROS) generation, whereas miR-29b-1-5p overexpression increases ROS generation and reduces cell proliferation. Moreover, NRF2 downregulates miR-29b-1-5p expression, whereas miR-29b-1-5p overexpression decreases p-AKT and p-NRF2. Furthermore, miR-29b-1-5p overexpression induces both inhibition of DNA N-methyltransferases (DNMT1, DNMT3A, and DNMT3B) expression and re-expression of HIN1, RASSF1A and CCND2. Conversely, NRF2 activation induces opposite effects. We also show that parthenolide, a naturally occurring small molecule, induces the expression of miR-29b-1-5p which could suppress NRF2 activation via AKT inhibition. Overall, this study uncovers a novel NRF2/miR-29b-1-5p/AKT regulatory loop that can regulate the fate (life/death) of MDA-MB-231 cells and suggests this loop as therapeutic target for TNBC.
Original languageEnglish
Pages (from-to)629-637
Number of pages9
JournalJournal of Cellular Physiology
Volume235
Publication statusPublished - 2020

All Science Journal Classification (ASJC) codes

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

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