title: Androgens downregulate miR-21 expression in breast cancer cells underlining the protective role of androgen receptor.
abstract: Although the protective role of androgen receptor (AR) in breast cancer (BC) is well established, the mechanisms involved remains largely unexplored. MicroRNAs play fundamental roles in many biological processes, including tumor cell development and metastasis. Herein, we report that androgens reduce BC cells proliferation acting as a negative modulator of the onco-miRNA-21.The synthetic androgen miboleron (Mib) decreases BC cell proliferation induced by miR-21 over-expression and AR knockdown evidenced the requirement of AR in the down-regulation of miR-21 expression. These effects seem to be a general mechanism occurring in BC tissues.Chromatin immune-precipitation (ChIP) analysis disclosed the binding of AR to a specific ARE sequence in miR-21 proximal promoter and recognizes the recruitment of HDAC3 as component for AR-mediated transcriptional repression. Such event is associated to a significantly reduced PolII binding in Mib treated extracts confirming that activated AR is a transcriptional repressor of miR-21 expression, providing further insight into the protective role of androgens in breast cancer cells.Collectively, our data and the widespread AR expression in primary and metastatic breast tumours, suggest a careful examination of the therapeutic potential of androgens also in potentiating the effectiveness of anti-oestrogen adjuvant therapies.
authors: Department of Pharmacy and Health and Nutritional Sciences, University of Calabria, Arcavacata di Rende (CS), Italy.
authors: Ivan
authors: I
authors: Casaburi
authors: Department of Pharmacy and Health and Nutritional Sciences, University of Calabria, Arcavacata di Rende (CS), Italy.
authors: Maria Grazia
authors: MG
authors: Cesario
authors: Department of Pharmacy and Health and Nutritional Sciences, University of Calabria, Arcavacata di Rende (CS), Italy.
authors: Ada
authors: A
authors: Donà
authors: Department of Pharmacy and Health and Nutritional Sciences, University of Calabria, Arcavacata di Rende (CS), Italy.
authors: Pietro
authors: P
authors: Rizza
authors: Department of Pharmacy and Health and Nutritional Sciences, University of Calabria, Arcavacata di Rende (CS), Italy.
authors: Saveria
authors: S
authors: Aquila
authors: Department of Pharmacy and Health and Nutritional Sciences, University of Calabria, Arcavacata di Rende (CS), Italy.
authors: Paola
authors: P
authors: Avena
authors: Department of Pharmacy and Health and Nutritional Sciences, University of Calabria, Arcavacata di Rende (CS), Italy.
authors: Marilena
authors: M
authors: Lanzino
authors: Department of Pharmacy and Health and Nutritional Sciences, University of Calabria, Arcavacata di Rende (CS), Italy.
authors: Michele
authors: M
authors: Pellegrino
authors: Department of Pharmacy and Health and Nutritional Sciences, University of Calabria, Arcavacata di Rende (CS), Italy.
authors: Adele
authors: A
authors: Vivacqua
authors: Department of Pharmacy and Health and Nutritional Sciences, University of Calabria, Arcavacata di Rende (CS), Italy.
authors: Paola
authors: P
authors: Tucci
authors: Department of Pharmacy and Health and Nutritional Sciences, University of Calabria, Arcavacata di Rende (CS), Italy.
authors: Catia
authors: C
authors: Morelli
authors: Department of Pharmacy and Health and Nutritional Sciences, University of Calabria, Arcavacata di Rende (CS), Italy.
authors: Sebastiano
authors: S
authors: Andò
authors: Department of Pharmacy and Health and Nutritional Sciences, University of Calabria, Arcavacata di Rende (CS), Italy.
authors: Diego
authors: D
authors: Sisci
mesh_terms: D000728:Androgens / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis* / Q000187:drug effects; D009277:Nandrolone / Q000031:analogs & derivatives* / Q000494:pharmacology; D011944:Receptors, Androgen / Q000378:metabolism*
chemical_list: C410798:AR protein, human; D000728:Androgens; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D011944:Receptors, Androgen; D009277:Nandrolone; C100075:mibolerone
keywords: androgen receptor; androgens; breast cancer; miR-21