ArticleOncogenesis2017
Context-dependent role for chromatin remodeling component PBRM1/BAF180 in clear cell renal cell carcinoma.
Article in Oncogenesis, 2017. 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, 34 citations in OpenAlex.
- A multi-programmed cell death-related LncRNA signature for prognosis and immune microenvironment evaluation in kidney renal clear cell carcinoma.Scientific reports · 2026Article
- CXCR4, CXCR7 and PBRM1 are responsible for everolimus and cabozantinib resistance in human renal cancer cells.Cell death discovery · 2026Article
- In vivo CRISPR/Cas9 screening identifies Pbrm1 as a regulator of myeloid leukemia development in mice.Blood advances · 2023Article
- The Effect of Hypoxia-inducible Factor Inhibition on the Phenotype of Fibroblasts in Human and Bovine Pulmonary Hypertension.American journal of respiratory cell and molecular biology · 2023Article
- PBRM1 bromodomains associate with RNA to facilitate chromatin association.Nucleic acids research · 2023Article
- PBRM1 deficiency oncogenic addiction is associated with activated AKT-mTOR signalling and aerobic glycolysis in clear cell renal cell carcinoma cells.Journal of cellular and molecular medicine · 2022Article
- Mutation spectrum associated with metastasis of advanced cholangiocarcinoma.The Journal of international medical research · 2022Article
- Identification and validation of an immune-related gene prognostic signature for clear cell renal carcinoma.Frontiers in immunology · 2022Article
- Involvement of PBRM1 in VHL disease-associated clear cell renal cell carcinoma and its putative relationship with the HIF pathway.Oncology letters · 2021Article
- DDIT4 S-Nitrosylation Aids p38-MAPK Signaling Complex Assembly to Promote Hepatic Reactive Oxygen Species Production.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Article
- Mechanisms Contributing to the Dysregulation of miRNA-124 in Pulmonary Hypertension.International journal of molecular sciences · 2021Article
- Targeting lysosome function causes selective cytotoxicity in VHL-inactivated renal cell carcinomas.Carcinogenesis · 2020Article
- Prognostic and Predictive Value ofCancers · 2019Review
- G Protein γ subunit 7 loss contributes to progression of clear cell renal cell carcinoma.Journal of cellular physiology · 2019Article
- New Insights into the Role of Polybromo-1 in Prostate Cancer.International journal of molecular sciences · 2019Article
- PBRM1 Regulates Stress Response in Epithelial Cells.iScience · 2019Article
- Mechanisms contributing to persistently activated cell phenotypes in pulmonary hypertension.The Journal of physiology · 2019Review
- Expression and Mutation Patterns of PBRM1, BAP1 and SETD2 Mirror Specific Evolutionary Subtypes in Clear Cell Renal Cell Carcinoma.Neoplasia (New York, N.Y.) · 2019Article
- Epigenetic modifiers: activities in renal cell carcinoma.Nature reviews. Urology · 2018Review
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
A subset of clear cell renal cell carcinoma (ccRCC) tumors exhibit a HIF1A gene mutation, yielding two ccRCC tumor types, H1H2 type expressing both HIF1α and HIF2α, and H2 type expressing HIF2α, but not functional HIF1α protein. However, it is unclear how the H1H2 type ccRCC tumors escape HIF1's tumor-suppressive activity. The polybromo-1 (PBRM1) gene coding for the BAF180 protein, a component of the SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling complex, is inactivated in 40% ccRCCs, the function and mechanism of BAF180 mutation is unknown. Our previous study indicates that BAF180-containing SWI/SNF chromatin remodeling complex is a co-activator for transcription factor HIF to induce HIF target genes. Thus, our questions are if BAF180 is involved in HIF-mediated hypoxia response and if PBRM1/BAF180 mutation has any association with the HIF1A retention in H1H2 type ccRCC. We report here that BAF180 is mutated in H1H2 ccRCC cell lines and tumors, and BAF180 re-expression in H1H2 ccRCC cell lines reduced cell proliferation/survival, indicating that BAF180 has tumor-suppressive role in these cells. However, BAF180 is expressed in HIF1-deficient H2 ccRCC cell lines and tumors, and BAF180 knockdown in H2 type ccRCC cell lines reduced cell proliferation/survival, indicating that BAF180 has tumor-promoting activity in these cells. In addition, our data show that BAF180 functions as co-activator for HIF1- and HIF2-mediated transcriptional response, and BAF180's tumor-suppressive and -promoting activity in ccRCC cell lines depends on co-expression of HIF1 and HIF2, respectively. Thus, our studies reveal that BAF180 function in ccRCC is context dependent, and that mutation of PBRM1/BAF180 serves as an alternative strategy for ccRCC tumors to reduce HIF1 tumor-suppressive activity in H1H2 ccRCC tumors. Our studies define distinct functional subgroups of ccRCCs based on expression of BAF180, and suggest that BAF180 inhibition may be a novel therapeutic target for patients with H2, but not H1H2, ccRCC tumors.
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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.