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. 2025 Jul:217:107785.
doi: 10.1016/j.phrs.2025.107785. Epub 2025 May 18.

Knockout of SIN3B modulates transcriptional programs and cell survival in cutaneous melanoma

Larissa Satiko Alcantara Sekimoto Matsuyama  1 , Victoria Harle  2 , Victoria Offord  2 , Alastair Droop  3 , Roy Rabbie  2 , Manik Garg  4 , Martha Estefania Vázquez-Cruz  5 , Carla Daniela Robles-Espinoza  5 , Gemma Turner  2 , David Fraser  2 , Érica Aparecida de Oliveira  6 , Danielle Gonçalves de Carvalho  7 , Natasha Andressa Nogueira Jorge  8 , Mariana Boroni  9 , Patricia A Possik  10 , David J Adams  2 , Silvya Stuchi Maria-Engler  11
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Free article

Knockout of SIN3B modulates transcriptional programs and cell survival in cutaneous melanoma

Larissa Satiko Alcantara Sekimoto Matsuyama et al. Pharmacol Res. 2025 Jul.
Free article

Abstract

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.

Keywords: CRISPR-Cas9; Melanoma; POLE4; SIN3B; STK11.

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Conflict of interest statement

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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