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

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

Risultato della ricerca: Article

1 Citazione (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.
Lingua originaleEnglish
Numero di pagine9
RivistaJournal of Cellular Physiology
Stato di pubblicazionePublished - 2019

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Triple Negative Breast Neoplasms
Chemical activation
Cells
Reactive Oxygen Species
Cell proliferation
Methyltransferases
Cell growth
Down-Regulation
Cell Proliferation
Cell Line
Molecules
DNA
Growth
Therapeutics

All Science Journal Classification (ASJC) codes

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

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

In: Journal of Cellular Physiology, 2019.

Risultato della ricerca: Article

Pratelli, Giovanni ; Di Fiore, Riccardo ; De Blasio, Anna ; Di Fiore, Riccardo ; Saliba, Christian ; Baldacchino, Shawn ; Vento, Renza ; Tesoriere, Giovanni ; Scerri, Christian ; Grech, Godfrey ; Drago Ferrante, Rosa. / A loop involving NRF2, miR-29b-1-5p and AKT, regulates cell fate of MDA-MB-231 triple-negative breast cancer cells. In: Journal of Cellular Physiology. 2019.
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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.",
author = "Giovanni Pratelli and {Di Fiore}, Riccardo and {De Blasio}, Anna and {Di Fiore}, Riccardo and Christian Saliba and Shawn Baldacchino and Renza Vento and Giovanni Tesoriere and Christian Scerri and Godfrey Grech and {Drago Ferrante}, Rosa",
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T1 - A loop involving NRF2, miR-29b-1-5p and AKT, regulates cell fate of MDA-MB-231 triple-negative breast cancer cells

AU - Pratelli, Giovanni

AU - Di Fiore, Riccardo

AU - De Blasio, Anna

AU - Di Fiore, Riccardo

AU - Saliba, Christian

AU - Baldacchino, Shawn

AU - Vento, Renza

AU - Tesoriere, Giovanni

AU - Scerri, Christian

AU - Grech, Godfrey

AU - Drago Ferrante, Rosa

PY - 2019

Y1 - 2019

N2 - 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.

AB - 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.

UR - http://hdl.handle.net/10447/363247

M3 - Article

JO - Journal of Cellular Physiology

JF - Journal of Cellular Physiology

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