학술논문
A loop involving NRF2, miR‐29b‐1‐5p and AKT, regulates cell fate of MDA‐MB‐231 triple‐negative breast cancer cells.
Document Type
Article
Author
Source
Subject
*TRIPLE-negative breast cancer
*CANCER cells
*SMALL molecules
*CELL growth
*TUMOR suppressor genes
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Language
ISSN
0021-9541
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. [ABSTRACT FROM AUTHOR]