ArticleBlood2014
Unbiased RNAi screen for hepcidin regulators links hepcidin suppression to proliferative Ras/RAF and nutrient-dependent mTOR signaling.
Article in Blood, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 73 citations in OpenAlex.
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- Alternative splicing remodeling and splicing factor regulatory networks define immune-associated molecular heterogeneity in dilated cardiomyopathy.Frontiers in bioinformatics · 2026Article
- The effect of the four pharmacological pillars of heart failure on haemoglobin level.Annals of medicine and surgery (2012) · 2024Review
- The association of TMPRSS6 gene polymorphism with iron status in Egyptian children (a pilot study).BMC pediatrics · 2024Article
- IL-6 signaling accelerates iron overload by upregulating DMT1 in endothelial cells to promote aortic dissection.International journal of biological sciences · 2024Article
- Exploration of novel clusters and prognostic value of immune‑related signatures and identify HAMP as hub gene in colorectal cancer.Oncology letters · 2023Article
- Duodenal macrophages control dietary iron absorption via local degradation of transferrin.Blood · 2023Article
- Review
- Distinctive modulation of hepcidin in cancer and its therapeutic relevance.Frontiers in oncology · 2023Review
- Iron accumulation and lipid peroxidation: implication of ferroptosis in hepatocellular carcinoma.Frontiers in endocrinology · 2023Review
- Hepatic HDAC3 Regulates Systemic Iron Homeostasis and Ferroptosis via the Hippo Signaling Pathway.Research (Washington, D.C.) · 2023Article
- Role of Iron in Aging Related Diseases.Antioxidants (Basel, Switzerland) · 2022Article
- Activation of STAT and SMAD Signaling Induces Hepcidin Re-Expression as a Therapeutic Target for β-Thalassemia Patients.Biomedicines · 2022Review
- An Integrated Systematic Analysis and the Clinical Significance of Hepcidin in Common Malignancies of the Male Genitourinary System.Frontiers in genetics · 2022Article
- The iron-modulating hormone hepcidin is upregulated and associated with poor survival outcomes in renal clear cell carcinoma.Frontiers in pharmacology · 2022Article
- Iron: an underrated factor in aging.Aging · 2021Article
- Association of common TMPRSS6 and TF gene variants with hepcidin and iron status in healthy rural Gambians.Scientific reports · 2021Article
- Iron metabolism and management: focus on chronic kidney disease.Kidney international supplements · 2021Article
- Article
- Loss of COPZ1 induces NCOA4 mediated autophagy and ferroptosis in glioblastoma cell lines.Oncogene · 2021Article
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Authors and funding
17 authors at 6 institutions in 2 countries.
Funding
Abstract
The hepatic hormone hepcidin is a key regulator of systemic iron metabolism. Its expression is largely regulated by 2 signaling pathways: the "iron-regulated" bone morphogenetic protein (BMP) and the inflammatory JAK-STAT pathways. To obtain broader insights into cellular processes that modulate hepcidin transcription and to provide a resource to identify novel genetic modifiers of systemic iron homeostasis, we designed an RNA interference (RNAi) screen that monitors hepcidin promoter activity after the knockdown of 19 599 genes in hepatocarcinoma cells. Interestingly, many of the putative hepcidin activators play roles in signal transduction, inflammation, or transcription, and affect hepcidin transcription through BMP-responsive elements. Furthermore, our work sheds light on new components of the transcriptional machinery that maintain steady-state levels of hepcidin expression and its responses to the BMP- and interleukin-6-triggered signals. Notably, we discover hepcidin suppression mediated via components of Ras/RAF MAPK and mTOR signaling, linking hepcidin transcriptional control to the pathways that respond to mitogen stimulation and nutrient status. Thus using a combination of RNAi screening, reverse phase protein arrays, and small molecules testing, we identify links between the control of systemic iron homeostasis and critical liver processes such as regeneration, response to injury, carcinogenesis, and nutrient metabolism.
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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.