ArticleCell death discovery2021
NR5A2 transcriptional activation by BRD4 promotes pancreatic cancer progression by upregulating GDF15.
Article in Cell death discovery, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 24 citations in OpenAlex.
- Exploring the Expanding Role of Nuclear Receptor LRH-1/NR5A2 in Cell Biology and Immunity.International journal of cell biology · 2026Review
- The Multifaceted Role of Growth Differentiation Factor 15 (GDF15): A Narrative Review from Cancer Cachexia to Target Therapy.Biomedicines · 2025Review
- Role of Protein Regulators of Cholesterol Homeostasis in Immune Modulation and Cancer Pathophysiology.Endocrinology · 2025Review
- NR5A2 (located on chromosome 1q32) inhibits ferroptosis and promotes drug resistance by regulating phospholipid remodeling in multiple myeloma.International journal of biological sciences · 2025Article
- Hepatocyte-specific NR5A2 deficiency induces pyroptosis and exacerbates non-alcoholic steatohepatitis by downregulating ALDH1B1 expression.Cell death & disease · 2024Article
- Whole-genome bisulfite sequencing identifies stage- and subtype-specific DNA methylation signatures in pancreatic cancer.iScience · 2024Article
- Article
- Regulome-wide association study identifies genetically driven accessible regions associated with pancreatic cancer risk.International journal of cancer · 2024Article
- Standigm ASK™: knowledge graph and artificial intelligence platform applied to target discovery in idiopathic pulmonary fibrosis.Briefings in bioinformatics · 2024Article
- Molecular basis of GDF15 induction and suppression by drugs in cardiomyocytes and cancer cells toward precision medicine.Scientific reports · 2023Article
- Overview of growth differentiation factor 15 in metabolic syndrome.Journal of cellular and molecular medicine · 2023Review
- Article
- BET inhibitors synergize with sunitinib in melanoma through GDF15 suppression.Experimental & molecular medicine · 2023Article
- Characterization of the Molecular Alterations Induced by the Prolonged Exposure of Normal Colon Mucosa and Colon Cancer Cells to Low-Dose Bisphenol A.International journal of molecular sciences · 2022Article
- Clinical usefulness and acceleratory effect of macrophage inhibitory cytokine-1 on biliary tract cancer: an experimental biomarker analysis.Cancer cell international · 2022Article
- Macrophage inhibitory cytokine-1 in cancer: Beyond the cellular phenotype.Cancer letters · 2022Review
- The regulatory landscape of retinoblastoma: a pathway analysis perspective.Royal Society open science · 2022Article
- Deubiquitination of FBP1 by USP7 blocks FBP1-DNMT1 interaction and decreases the sensitivity of pancreatic cancer cells to PARP inhibitors.Molecular oncology · 2022Article
- Pathophysiological role of growth differentiation factor 15 (GDF15) in obesity, cancer, and cachexia.Cytokine & growth factor reviews · 2022Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
NR5A2 is a transcription factor regulating the expression of various oncogenes. However, the role of NR5A2 and the specific regulatory mechanism of NR5A2 in pancreatic ductal adenocarcinoma (PDAC) are not thoroughly studied. In our study, Western blotting, real-time PCR, and immunohistochemistry were conducted to assess the expression levels of different molecules. Wound-healing, MTS, colony formation, and transwell assays were employed to evaluate the malignant potential of pancreatic cancer cells. We demonstrated that NR5A2 acted as a negative prognostic biomarker in PDAC. NR5A2 silencing inhibited the proliferation and migration abilities of pancreatic cancer cells in vitro and in vivo. While NR5A2 overexpression markedly promoted both events in vitro. We further identified that NR5A2 was transcriptionally upregulated by BRD4 in pancreatic cancer cells and this was confirmed by Chromatin immunoprecipitation (ChIP) and ChIP-qPCR. Besides, transcriptome RNA sequencing (RNA-Seq) was performed to explore the cancer-promoting effects of NR5A2, we found that GDF15 is a component of multiple down-regulated tumor-promoting gene sets after NR5A2 was silenced. Next, we showed that NR5A2 enhanced the malignancy of pancreatic cancer cells by inducing the transcription of GDF15. Collectively, our findings suggest that NR5A2 expression is induced by BRD4. In turn, NR5A2 activates the transcription of GDF15, promoting pancreatic cancer progression. Therefore, NR5A2 and GDF15 could be promising therapeutic targets in pancreatic cancer.
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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.