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National Institute of Environmental Health Sciences

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Publication Detail

Title: Dehydroepiandrosterone-induces miR-21 transcription in HepG2 cells through estrogen receptor β and androgen receptor.

Authors: Teng, Yun; Litchfield, Lacey M; Ivanova, Margarita M; Prough, Russell A; Clark, Barbara J; Klinge, Carolyn M

Published In Mol Cell Endocrinol, (2014 Jul 5)

Abstract: Although oncomiR miR-21 is highly expressed in liver and overexpressed in hepatocellular carcinoma (HCC), its regulation is uncharacterized. We examined the effect of physiologically relevant nanomolar concentrations of dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEA-S) on miR-21 expression in HepG2 human hepatoma cells. 10nM DHEA and DHEA-S increase pri-miR-21 transcription in HepG2 cells. Dietary DHEA increased miR-21 in vivo in mouse liver. siRNA and inhibitor studies suggest that DHEA-S requires desulfation for activity and that DHEA-induced pri-miR-21 transcription involves metabolism to androgen and estrogen receptor (AR and ER) ligands. Activation of ERβ and AR by DHEA metabolites androst-5-ene-3,17-dione (ADIONE), androst-5-ene-3β,17β-diol (ADIOL), dihydrotestosterone (DHT), and 5α-androstane-3β,17β-diol (3β-Adiol) increased miR-21 transcription. DHEA-induced miR-21 increased cell proliferation and decreased Pdcd4 protein, a bona fide miR-21. Estradiol (E2) inhibited miR-21 expression via ERα. DHEA increased ERβ and AR recruitment to the miR-21 promoter within the VMP1/TMEM49 gene, with possible significance in hepatocellular carcinoma.

PubMed ID: 24845419 Exiting the NIEHS site

MeSH Terms: Animals; Apoptosis Regulatory Proteins/genetics; Apoptosis Regulatory Proteins/metabolism; Base Sequence; Cell Proliferation/drug effects; Cell Survival/drug effects; Cell Survival/genetics; Dehydroepiandrosterone/pharmacology*; Estrogen Receptor beta/antagonists & inhibitors; Estrogen Receptor beta/metabolism*; Gene Expression Regulation, Neoplastic/drug effects; Gene Knockdown Techniques; Hep G2 Cells; Humans; Male; Mice, Inbred C57BL; MicroRNAs/genetics*; MicroRNAs/metabolism; Molecular Sequence Data; Promoter Regions, Genetic/genetics; Protein Binding/drug effects; RNA, Messenger/genetics; RNA, Messenger/metabolism; RNA-Binding Proteins/genetics; RNA-Binding Proteins/metabolism; Receptors, Androgen/metabolism*; Transcription, Genetic/drug effects*; Up-Regulation/drug effects; Up-Regulation/genetics

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