PMID- 24845419 OWN - NLM STAT- MEDLINE DCOM- 20150219 LR - 20211021 IS - 1872-8057 (Electronic) IS - 0303-7207 (Print) IS - 0303-7207 (Linking) VI - 392 IP - 1-2 DP - 2014 Jul 5 TI - Dehydroepiandrosterone-induces miR-21 transcription in HepG2 cells through estrogen receptor beta and androgen receptor. PG - 23-36 LID - S0303-7207(14)00149-X [pii] LID - 10.1016/j.mce.2014.05.007 [doi] AB - 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 ERbeta and AR by DHEA metabolites androst-5-ene-3,17-dione (ADIONE), androst-5-ene-3beta,17beta-diol (ADIOL), dihydrotestosterone (DHT), and 5alpha-androstane-3beta,17beta-diol (3beta-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 ERalpha. DHEA increased ERbeta and AR recruitment to the miR-21 promoter within the VMP1/TMEM49 gene, with possible significance in hepatocellular carcinoma. CI - Copyright (c) 2014 Elsevier Ireland Ltd. All rights reserved. FAU - Teng, Yun AU - Teng Y AD - Department of Biochemistry & Molecular Biology, Center for Genetics and Molecular Medicine, University of Louisville School of Medicine, Louisville, KY 40292, USA. FAU - Litchfield, Lacey M AU - Litchfield LM AD - Department of Biochemistry & Molecular Biology, Center for Genetics and Molecular Medicine, University of Louisville School of Medicine, Louisville, KY 40292, USA. FAU - Ivanova, Margarita M AU - Ivanova MM AD - Department of Biochemistry & Molecular Biology, Center for Genetics and Molecular Medicine, University of Louisville School of Medicine, Louisville, KY 40292, USA. FAU - Prough, Russell A AU - Prough RA AD - Department of Biochemistry & Molecular Biology, Center for Genetics and Molecular Medicine, University of Louisville School of Medicine, Louisville, KY 40292, USA. FAU - Clark, Barbara J AU - Clark BJ AD - Department of Biochemistry & Molecular Biology, Center for Genetics and Molecular Medicine, University of Louisville School of Medicine, Louisville, KY 40292, USA. FAU - Klinge, Carolyn M AU - Klinge CM AD - Department of Biochemistry & Molecular Biology, Center for Genetics and Molecular Medicine, University of Louisville School of Medicine, Louisville, KY 40292, USA. Electronic address: carolyn.klinge@louisville.edu. LA - eng GR - R01 CA138410/CA/NCI NIH HHS/United States GR - T32 ES011564/ES/NIEHS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20140517 PL - Ireland TA - Mol Cell Endocrinol JT - Molecular and cellular endocrinology JID - 7500844 RN - 0 (AR protein, human) RN - 0 (Apoptosis Regulatory Proteins) RN - 0 (Estrogen Receptor beta) RN - 0 (MIRN21 microRNA, human) RN - 0 (MicroRNAs) RN - 0 (PDCD4 protein, human) RN - 0 (RNA, Messenger) RN - 0 (RNA-Binding Proteins) RN - 0 (Receptors, Androgen) RN - 459AG36T1B (Dehydroepiandrosterone) SB - IM MH - Animals MH - Apoptosis Regulatory Proteins/genetics/metabolism MH - Base Sequence MH - Cell Proliferation/drug effects MH - Cell Survival/drug effects/genetics MH - Dehydroepiandrosterone/*pharmacology MH - Estrogen Receptor beta/antagonists & inhibitors/*metabolism MH - Gene Expression Regulation, Neoplastic/drug effects MH - Gene Knockdown Techniques MH - Hep G2 Cells MH - Humans MH - Male MH - Mice, Inbred C57BL MH - MicroRNAs/*genetics/metabolism MH - Molecular Sequence Data MH - Promoter Regions, Genetic/genetics MH - Protein Binding/drug effects MH - RNA, Messenger/genetics/metabolism MH - RNA-Binding Proteins/genetics/metabolism MH - Receptors, Androgen/*metabolism MH - Transcription, Genetic/*drug effects MH - Up-Regulation/drug effects/genetics PMC - PMC4074919 MID - NIHMS600479 OTO - NOTNLM OT - Androgen receptor OT - DHEA OT - Estrogen receptor OT - HepG2 cells OT - microRNA EDAT- 2014/05/23 06:00 MHDA- 2015/02/20 06:00 PMCR- 2015/07/05 CRDT- 2014/05/22 06:00 PHST- 2014/01/17 00:00 [received] PHST- 2014/05/02 00:00 [revised] PHST- 2014/05/09 00:00 [accepted] PHST- 2014/05/22 06:00 [entrez] PHST- 2014/05/23 06:00 [pubmed] PHST- 2015/02/20 06:00 [medline] PHST- 2015/07/05 00:00 [pmc-release] AID - S0303-7207(14)00149-X [pii] AID - 10.1016/j.mce.2014.05.007 [doi] PST - ppublish SO - Mol Cell Endocrinol. 2014 Jul 5;392(1-2):23-36. doi: 10.1016/j.mce.2014.05.007. Epub 2014 May 17.