PMID- 31313842 OWN - NLM STAT- MEDLINE DCOM- 20201013 LR - 20231213 IS - 1097-4652 (Electronic) IS - 0021-9541 (Linking) VI - 235 IP - 2 DP - 2020 Feb TI - A loop involving NRF2, miR-29b-1-5p and AKT, regulates cell fate of MDA-MB-231 triple-negative breast cancer cells. PG - 629-637 LID - 10.1002/jcp.29062 [doi] 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. CI - (c) 2019 Wiley Periodicals, Inc. FAU - De Blasio, Anna AU - De Blasio A AUID- ORCID: 0000-0003-2208-0366 AD - Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), Laboratory of Biochemistry (Polyclinic), University of Palermo, Palermo, Italy. FAU - Di Fiore, Riccardo AU - Di Fiore R AUID- ORCID: 0000-0003-4905-6948 AD - Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), Laboratory of Biochemistry (Polyclinic), University of Palermo, Palermo, Italy. AD - Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, College of Science and Technology, Temple University, Philadelphia, Pennsylvania. FAU - Pratelli, Giovanni AU - Pratelli G AD - Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), Laboratory of Biochemistry (Polyclinic), University of Palermo, Palermo, Italy. FAU - Drago-Ferrante, Rosa AU - Drago-Ferrante R AD - Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), Laboratory of Biochemistry (Polyclinic), University of Palermo, Palermo, Italy. FAU - Saliba, Christian AU - Saliba C AD - Centre for Molecular Medicine and Biobanking, University of Malta, Msida, Malta. FAU - Baldacchino, Shawn AU - Baldacchino S AD - Department of Pathology, Faculty of Medicine and Surgery, University of Malta, Msida, Malta. FAU - Grech, Godfrey AU - Grech G AD - Department of Pathology, Faculty of Medicine and Surgery, University of Malta, Msida, Malta. FAU - Scerri, Christian AU - Scerri C AD - Department of Physiology and Biochemistry, Faculty of Medicine and Surgery, University of Malta, Msida, Malta. FAU - Vento, Renza AU - Vento R AUID- ORCID: 0000-0002-8308-4830 AD - Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, College of Science and Technology, Temple University, Philadelphia, Pennsylvania. FAU - Tesoriere, Giovanni AU - Tesoriere G AD - Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, College of Science and Technology, Temple University, Philadelphia, Pennsylvania. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190710 PL - United States TA - J Cell Physiol JT - Journal of cellular physiology JID - 0050222 RN - 0 (CCND2 protein, human) RN - 0 (Cyclin D2) RN - 0 (DNMT3A protein, human) RN - 0 (MIRN29a microRNA, human) RN - 0 (MicroRNAs) RN - 0 (NF-E2-Related Factor 2) RN - 0 (NFE2L2 protein, human) RN - 0 (RASSF1 protein, human) RN - 0 (Reactive Oxygen Species) RN - 0 (Sesquiterpenes) RN - 0 (Tumor Suppressor Proteins) RN - 2RDB26I5ZB (parthenolide) RN - EC 2.1.1.37 (DNA (Cytosine-5-)-Methyltransferase 1) RN - EC 2.1.1.37 (DNA (Cytosine-5-)-Methyltransferases) RN - EC 2.1.1.37 (DNA Methyltransferase 3A) RN - EC 2.1.1.37 (DNMT1 protein, human) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) SB - IM MH - Cell Line, Tumor MH - Cell Proliferation/genetics MH - Cyclin D2/metabolism MH - DNA (Cytosine-5-)-Methyltransferase 1/metabolism MH - DNA (Cytosine-5-)-Methyltransferases/metabolism MH - DNA Methylation/genetics MH - DNA Methyltransferase 3A MH - Female MH - Gene Expression Regulation, Neoplastic/genetics MH - Humans MH - MicroRNAs/*genetics MH - NF-E2-Related Factor 2/*genetics MH - Proto-Oncogene Proteins c-akt/*genetics MH - Reactive Oxygen Species/metabolism MH - Sesquiterpenes/pharmacology MH - Signal Transduction/genetics MH - Triple Negative Breast Neoplasms/drug therapy/*genetics/pathology MH - Tumor Suppressor Proteins/metabolism MH - DNA Methyltransferase 3B OTO - NOTNLM OT - AKT OT - DNMTs OT - NRF2 OT - miR-29b-1-5p OT - parthenolide OT - tumor suppressor genes EDAT- 2019/07/18 06:00 MHDA- 2020/10/21 06:00 CRDT- 2019/07/18 06:00 PHST- 2019/04/26 00:00 [received] PHST- 2019/06/20 00:00 [accepted] PHST- 2019/07/18 06:00 [pubmed] PHST- 2020/10/21 06:00 [medline] PHST- 2019/07/18 06:00 [entrez] AID - 10.1002/jcp.29062 [doi] PST - ppublish SO - J Cell Physiol. 2020 Feb;235(2):629-637. doi: 10.1002/jcp.29062. Epub 2019 Jul 10.