ArticleOncogene2015
LRH-1 controls proliferation in breast tumor cells by regulating CDKN1A gene expression.
Article in Oncogene, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 65 citations in OpenAlex.
- Accurate Prediction of Central Conventional Chondrosarcoma Risk and Outcome Using Methylation Profiling: CHROME.Genes, chromosomes & cancer · 2026Article
- Role of Protein Regulators of Cholesterol Homeostasis in Immune Modulation and Cancer Pathophysiology.Endocrinology · 2025Review
- p53R172H and p53R245W Hotspot Mutations Drive Distinct Transcriptomes in Mouse Mammary Tumors Through a Convergent Transcriptional Mediator.Cancer research communications · 2024Article
- Liver receptor homolog-1: structures, related diseases, and drug discovery.Acta pharmacologica Sinica · 2024Review
- An uncertainty-based interpretable deep learning framework for predicting breast cancer outcome.BMC bioinformatics · 2024Article
- Inhibiting NR5A2 targets stemness in pancreatic cancer by disrupting SOX2/MYC signaling and restoring chemosensitivity.Journal of experimental & clinical cancer research : CR · 2023Article
- MicroRNA-433-3p enhances chemosensitivity of glioma to cisplatin by downregulating NR5A2.Brain and behavior · 2022Article
- Differential Modulation of Nuclear Receptor LRH-1 through Targeting Buried and Surface Regions of the Binding Pocket.Journal of medicinal chemistry · 2022Article
- MicroRNA-96: A therapeutic and diagnostic tumor marker.Iranian journal of basic medical sciences · 2022Review
- Nuclear receptor NR5A2 negatively regulates cell proliferation and tumor growth in nervous system malignancies.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- NR5A2 transcriptional activation by BRD4 promotes pancreatic cancer progression by upregulating GDF15.Cell death discovery · 2021Article
- A role for orphan nuclear receptor liver receptor homolog-1 (LRH-1, NR5A2) in primordial follicle activation.Scientific reports · 2021Article
- MicroRNA-219-5p participates in cyanotic congenital heart disease progression by regulating cardiomyocyte apoptosis.Experimental and therapeutic medicine · 2021Article
- LRH1 Acts as an Oncogenic Driver in Human Osteosarcoma and Pan-Cancer.Frontiers in cell and developmental biology · 2021Article
- Prediction of blood-based biomarkers and subsequent design of bisulfite PCR-LDR-qPCR assay for breast cancer detection.BMC cancer · 2020Article
- LRH1 Promotes Tumor Cell Proliferation and Migration and Is Correlated With Poor Prognosis in Ovarian Cancer.Frontiers in oncology · 2020Article
- Nr5a2 promotes cancer stem cell properties and tumorigenesis in nonsmall cell lung cancer by regulating Nanog.Cancer medicine · 2019Article
- Nr5a2 promotes tumor growth and metastasis of gastric cancer AGS cells by Wnt/beta-catenin signaling.OncoTargets and therapy · 2019Article
- LRH1 as a promising prognostic biomarker and predictor of metastasis in patients with non-small cell lung cancer.Thoracic cancer · 2018Article
- Chemotherapy-driven increases in the CDKN1A/PTN/PTPRZ1 axis promote chemoresistance by activating the NF-κB pathway in breast cancer cells.Cell communication and signaling : CCS · 2018Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Liver receptor homolog-1 (LRH-1, NR5A2) is an orphan nuclear receptor that has an essential role in cancer progression, notably in breast cancer. Although its role in promoting cancer cell proliferation and migration is well documented, the molecular basis is not completely established. Here, we report that LRH-1 inhibition affects two- and three-dimensional cell proliferation of different types of breast cancer cells, including estrogen receptor α (ERα)-positive and triple-negative cells. This phenotype is accompanied by the upregulation of the cyclin-dependent kinase inhibitor CDKN1A (aka p21(CIP1/WAF1)) in a p53-independent manner. Chromatin immunoprecipitation analysis shows that LRH-1 cooperates with FOXA1 and binds directly to CDKN1A promoter and a distal regulatory region found at -62 kb from its transcriptional start sites, allowing repression of CDKN1A transcription. LRH-1 or FOXA1 depletion induces CDKN1A upregulation by removing histone deacetylase 2 from the promoter and distal regulatory elements and permitting histone acetylation in these regions. Analysis of breast cancer samples reveals that a high LRH-1 level is inversely correlated with CDKN1A expression in breast cancer patients and is associated with poor prognosis. This study reveals a novel mechanism of control of cell proliferation by LRH-1 regulating CDKN1A transcription in breast cancer cells, independent of ERα and p53 status. Targeting LRH-1 may provide an attractive prospect for treatment of tumors that are resistant to hormonal and targeted therapy.
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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.