AI Article Synopsis
- The study investigates how dehydroepiandrosterone (DHEA) and its sulfate form (DHEA-S) affect the expression of the microRNA miR-21 in liver cells, especially concerning its role in hepatocellular carcinoma (HCC).
- Both DHEA and DHEA-S increase the transcription of pri-miR-21 in HepG2 cells, and dietary DHEA elevates miR-21 levels in mice.
- The research suggests that DHEA metabolism to androgen and estrogen receptor ligands is necessary for its effect on miR-21, which is linked to increased cell proliferation and decreased levels of the protein Pdcd4, known to be regulated by miR-
Article 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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4074919 | PMC |
| http://dx.doi.org/10.1016/j.mce.2014.05.007 | DOI Listing |
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