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Estrogen and retinoic acid antagonistically regulate several microRNA genes to control aerobic glycolysis in breast cancer cells.
MedLine Citation:
PMID:  23064179     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
In addition to estrogen receptor modulators, retinoic acid and other retinoids are promising agents to prevent breast cancer. Retinoic acid and estrogen exert antagonistic regulations on the transcription of coding genes and we evaluated here whether these two compounds have similar effects on microRNAs. Using an integrative approach based on several bioinformatics resources together with experimental validations, we indeed found that retinoic acid positively regulates miR-210 and miR-23a/24-2 expressions and is counteracted by estrogen. Conversely, estrogen increased miR-17/92 and miR-424/450b expressions and is inhibited by retinoic acid. In silico functional enrichment further revealed that this combination of transcriptional/post-transcriptional regulations fully impacts on the molecular effects of estrogen and retinoic acid. Besides, we unveiled a novel effect of retinoic acid on aerobic glycolysis. We specifically showed that it increases extracellular lactate production, an effect counteracted by the miR-210 and the miR-23a/24-2, which simultaneously target lactate dehydrogenase A and B mRNAs. Together our results provide a new framework to better understand the estrogen/retinoic acid antagonism in breast cancer cells.
Authors:
Anne Saumet; Guillaume Vetter; Manuella Bouttier; Etienne Antoine; Christine Roubert; Beatrice Orsetti; Charles Theillet; Charles-Henri Lecellier
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-10-12
Journal Detail:
Title:  Molecular bioSystems     Volume:  -     ISSN:  1742-2051     ISO Abbreviation:  Mol Biosyst     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-15     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101251620     Medline TA:  Mol Biosyst     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
INSERM U896, F-34298Montpellier, France.
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