Knockout of SIN3B modulates transcriptional programs and cell survival in cutaneous melanoma
SIN3 is a critical component of the histone deacetylase complex. Utilizing whole transcriptome data from melanoma patient samples we reveal that elevated levels of SIN3B are associated with poor survival outcomes with in vitro studies showing increased SIN3B expression in BRAF-mutant metastatic melanoma cell lines. The generation of isogenic SIN3B knockout cell lines indicated that SIN3B disruption led to a decrease in pathways associated with tumor invasion, migration, and cell-cell interactions. Moreover, pooled genome-wide CRISPR/Cas9 screens highlighted POLE4 and STK11 as crucial for the fitness and survival of SIN3B-knockout melanoma cells suggesting a role for these genes in epistasis with SIN3B. In summary, our findings suggest that SIN3B plays a pivotal role in modulating the behavior of melanoma cells, with implications for tumor growth and response to therapy.
Authors
- Silvya Stuchi Maria–Engler (ORCID: https://orcid.org/0000-0003-4771-6041)
- Natasha Andressa Nogueira Jorge (ORCID: https://orcid.org/0000-0001-5200-8707)
- Danielle Gonçalves de Carvalho
- Victoria Offord (ORCID: https://orcid.org/0000-0003-3104-317X)
- Mariana Boroni (ORCID: https://orcid.org/0000-0003-3495-9917)
- Larissa Satiko Alcântara Sekimoto Matsuyama (ORCID: https://orcid.org/0000-0002-5610-0030)
- Martha Estefania Vázquez‐Cruz (ORCID: https://orcid.org/0009-0007-7111-109X)
- Carla Daniela Robles‐Espinoza (ORCID: https://orcid.org/0000-0003-3277-7466)
- Érica A. Oliveira (ORCID: https://orcid.org/0000-0002-1624-4021)
- Patrícia A. Possik (ORCID: https://orcid.org/0000-0003-2899-0969)
- Victoria Harle (ORCID: https://orcid.org/0000-0002-5953-4766)
- Roy Rabbie (ORCID: https://orcid.org/0000-0002-9195-5659)
- Alastair Droop (ORCID: https://orcid.org/0000-0001-7695-7480)
- Manik Garg (ORCID: https://orcid.org/0000-0003-0453-2058)
- David J. Adams (ORCID: https://orcid.org/0000-0001-9490-0306)
- Gemma Turner
- David B. Fraser
Institutions
- European Bioinformatics Institute (GB)
- Universidade de São Paulo (BR)
- Wellcome Sanger Institute (GB)
- Instituto do Câncer do Estado de São Paulo (BR)
- Hospital do Câncer III (BR)
- Instituto Nacional de Câncer - INCA (BR)
- Institute of Bioinformatics (IN)
- University of York (GB)
- Universidad Nacional Autónoma de México (MX)
Publication Details
- Journal
- Pharmacological Research
- Published
- 2025-05-18
- DOI
- https://doi.org/10.1016/j.phrs.2025.107785
- Primary Topic
- Histone Deacetylase Inhibitors Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Wellcome
- Fundação de Amparo à Pesquisa do Estado de São Paulo
- Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
- Conselho Nacional de Desenvolvimento Científico e Tecnológico
- Medical Research Council