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RESEARCH PRODUCT
A loop involving NRF2, miR‐29b‐1‐5p and AKT, regulates cell fate of MDA‐MB‐231 triple‐negative breast cancer cells
Giovanni TesoriereShawn BaldacchinoAnna De BlasioRenza VentoRiccardo Di FioreRiccardo Di FioreGiovanni PratelliChristian ScerriGodfrey GrechRosa Drago-ferranteChristian Salibasubject
DNA (Cytosine-5-)-Methyltransferase 10301 basic medicineNF-E2-Related Factor 2PhysiologyClinical BiochemistryTriple Negative Breast NeoplasmsAKT DNMTs miR‐29b‐1‐5p NRF2 parthenolide tumor suppressor genesCell fate determinationenvironment and public healthDNA Methyltransferase 3A03 medical and health scienceschemistry.chemical_compound0302 clinical medicineSettore BIO/10 - BiochimicaCell Line TumorCyclin D2HumansParthenolideDNA (Cytosine-5-)-MethyltransferasesProtein kinase BTriple-negative breast cancerCell Proliferationchemistry.chemical_classificationReactive oxygen speciesCell growthTumor Suppressor ProteinsCell BiologyDNA Methylationrespiratory systemCell biologyGene Expression Regulation NeoplasticMicroRNAs030104 developmental biologychemistryCell culture030220 oncology & carcinogenesisDNMT1FemaleReactive Oxygen SpeciesProto-Oncogene Proteins c-aktSesquiterpenesSignal Transductiondescription
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2019-04-26 | Journal of Cellular Physiology |