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

Authors :
Giovanni Tesoriere
Shawn Baldacchino
Anna De Blasio
Renza Vento
Riccardo Di Fiore
Giovanni Pratelli
Christian Scerri
Godfrey Grech
Rosa Drago-Ferrante
Christian Saliba
De Blasio A, Di Fiore R, Pratelli G, Drago-Ferrante R, Saliba C, Baldacchino S, Grech G, Scerri C, Vento R, Tesoriere G.
Source :
Journal of Cellular Physiology. 235:629-637
Publication Year :
2019
Publisher :
Wiley, 2019.

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.

Details

ISSN :
10974652 and 00219541
Volume :
235
Database :
OpenAIRE
Journal :
Journal of Cellular Physiology
Accession number :
edsair.doi.dedup.....86f2593b0b5be11b52eca3f923206c8e