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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
- 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.
- Subjects :
- DNA (Cytosine-5-)-Methyltransferase 1
0301 basic medicine
NF-E2-Related Factor 2
Physiology
Clinical Biochemistry
Triple Negative Breast Neoplasms
AKT, DNMTs, miR‐29b‐1‐5p, NRF2, parthenolide, tumor suppressor genes
Cell fate determination
environment and public health
DNA Methyltransferase 3A
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Settore BIO/10 - Biochimica
Cell Line, Tumor
Cyclin D2
Humans
Parthenolide
DNA (Cytosine-5-)-Methyltransferases
Protein kinase B
Triple-negative breast cancer
Cell Proliferation
chemistry.chemical_classification
Reactive oxygen species
Cell growth
Tumor Suppressor Proteins
Cell Biology
DNA Methylation
respiratory system
Cell biology
Gene Expression Regulation, Neoplastic
MicroRNAs
030104 developmental biology
chemistry
Cell culture
030220 oncology & carcinogenesis
DNMT1
Female
Reactive Oxygen Species
Proto-Oncogene Proteins c-akt
Sesquiterpenes
Signal Transduction
Subjects
Details
- ISSN :
- 10974652 and 00219541
- Volume :
- 235
- Database :
- OpenAIRE
- Journal :
- Journal of Cellular Physiology
- Accession number :
- edsair.doi.dedup.....86f2593b0b5be11b52eca3f923206c8e