ArticleThe Journal of biological chemistry2015
Dehydroepiandrosterone Activation of G-protein-coupled Estrogen Receptor Rapidly Stimulates MicroRNA-21 Transcription in Human Hepatocellular Carcinoma Cells.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
27 citing papers in PubMed, 59 citations in OpenAlex.
- Anti-aging effects of the adrenal androgens dehydroepiandrosterone and dehydroepiandrosterone sulfate: mechanisms of action and beneficial effects in older people.Endocrine journal · 2026Review
- Endocrine therapy resistance of breast cancer: Important role of G protein-coupled estrogen receptor (GPER) and new therapeutic strategies.Genes & diseases · 2026Review
- The role of neuroactive steroids in psychiatric and neurological disorders: Neurobiology and therapeutic perspectives.Neuroscience and biobehavioral reviews · 2025Review
- Anti-Tumour Immunity Relies on Targeting Tissue Homeostasis Through Monocyte-Driven Responses Rather Than Direct Tumour Cytotoxicity.Liver international : official journal of the International Association for the Study of the Liver · 2025Article
- The G protein-coupled oestrogen receptor GPER in health and disease: an update.Nature reviews. Endocrinology · 2023Review
- Comparative G-Protein-Coupled Estrogen Receptor (GPER) Systems in Diabetic and Cancer Conditions: A Review.Molecules (Basel, Switzerland) · 2022Review
- Dehydroepiandrosterone exacerbates nigericin-induced abnormal autophagy and pyroptosis via GPER activation in LPS-primed macrophages.Cell death & disease · 2022Article
- DHEA Protects Human Cholangiocytes and Hepatocytes against Apoptosis and Oxidative Stress.Cells · 2022Article
- Increased serum concentrations of estrogen-induced growth factors Midkine and FGF2 in NF1 patients with plexiform neurofibroma.American journal of translational research · 2022Article
- HNRNPA2B1 regulates tamoxifen- and fulvestrant-sensitivity and hallmarks of endocrine resistance in breast cancer cells.Cancer letters · 2021Article
- Lithocholic Acid Induces miR21, Promoting PTEN Inhibition via STAT3 and ERK-1/2 Signaling in Colorectal Cancer Cells.International journal of molecular sciences · 2021Article
- Role of G Protein-Coupled Estrogen Receptor in Digestive System Carcinomas: A Minireview.OncoTargets and therapy · 2021Review
- Perspectives on the Role of Non-Coding RNAs in the Regulation of Expression and Function of the Estrogen Receptor.Cancers · 2020Review
- Low serum albumin, aspartate aminotransferase, and body mass are risk factors for frailty in elderly people with diabetes-a cross-sectional study.BMC geriatrics · 2020Article
- Effect of estrogen-active compounds on the expression of RACK1 and immunological implications.Archives of toxicology · 2020Article
- GPER and Testicular Germ Cell Cancer.Frontiers in endocrinology · 2020Review
- G Protein-Coupled Estrogen Receptor in Immune Cells and Its Role in Immune-Related Diseases.Frontiers in endocrinology · 2020Review
- miR‑21‑5p ameliorates hyperoxic acute lung injury and decreases apoptosis of AEC II cells via PTEN/AKT signaling in rats.Molecular medicine reports · 2019Article
- Hsa_circ_0101432 promotes the development of hepatocellular carcinoma (HCC) by adsorbing miR-1258 and miR-622.Cell cycle (Georgetown, Tex.) · 2019Article
- Role of purinergic receptors in hepatobiliary carcinoma in Pakistani population: an approach towards proinflammatory role of P2X4 and P2X7 receptors.Purinergic signalling · 2019Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
Little is known about the regulation of the oncomiR miR-21 in liver. Dehydroepiandrosterone (DHEA) regulates gene expression as a ligand for a G-protein-coupled receptor and as a precursor for steroids that activate nuclear receptor signaling. We report that 10 nm DHEA increases primary miR-21 (pri-miR-21) transcription and mature miR-21 expression in HepG2 cells in a biphasic manner with an initial peak at 1 h followed by a second, sustained response from 3-12 h. DHEA also increased miR-21 in primary human hepatocytes and Hep3B cells. siRNA, antibody, and inhibitor studies suggest that the rapid DHEA-mediated increase in miR-21 involves a G-protein-coupled estrogen receptor (GPER/GPR30), estrogen receptor α-36 (ERα36), epidermal growth factor receptor-dependent, pertussis toxin-sensitive pathway requiring activation of c-Src, ERK1/2, and PI3K. GPER antagonist G-15 attenuated DHEA- and BSA-conjugated DHEA-stimulated pri-miR-21 transcription. Like DHEA, GPER agonists G-1 and fulvestrant increased pri-miR-21 in a GPER- and ERα36-dependent manner. DHEA, like G-1, increased GPER and ERα36 mRNA and protein levels. DHEA increased ERK1/2 and c-Src phosphorylation in a GPER-responsive manner. DHEA increased c-Jun, but not c-Fos, protein expression after 2 h. DHEA increased androgen receptor, c-Fos, and c-Jun recruitment to the miR-21 promoter. These results suggest that physiological concentrations of DHEA activate a GPER intracellular signaling cascade that increases pri-miR-21 transcription mediated at least in part by AP-1 and androgen receptor miR-21 promoter interaction.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.