1. SNF5 deficiency induces apoptosis resistance by repressing SATB1 expression in Sézary syndrome.
- Author
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Li Y, Wang J, Yu M, Wang Y, Zhang H, Yin J, Li Z, Li T, Yan H, Li F, and Wang X
- Subjects
- Animals, Cell Line, Tumor, Fibroblasts, HEK293 Cells, Humans, Matrix Attachment Region Binding Proteins metabolism, Mice, SMARCB1 Protein genetics, Sezary Syndrome pathology, Apoptosis genetics, Gene Expression Regulation, Neoplastic, Matrix Attachment Region Binding Proteins genetics, SMARCB1 Protein metabolism, Sezary Syndrome genetics
- Abstract
SNF5, is a core member of the SWI/SNF chromatin remodeling complex. It's deficiency leads to multiple types of aggressive cancer. Sézary syndrome, a leukemic variant of cutaneous T-cell lymphoma, is characterized by its resistance to apoptosis. Although the cause of apoptosis resistance is still poorly understood, recent evidence has revealed the importance of SATB1 in the apoptosis resistance of Sézary syndrome. In this study, we show that SNF5 is an upstream regulator of SATB1 in several conditions and that both are deficient in Sézary cells. Additionally, SNF5 not only controls the expression of SATB1, but also utilizes SATB1 to recruit itself to specific sites. Overexpression of SNF5 induces SATB1 expression and partially reverse apoptosis resistance phenotype in Sézary cells. These results suggest that both SNF5 and SATB1 may regulate apoptosis-related genes in Sézary syndrome. Thus, targeting SWI/SNF complex may represent a promising approach for Sézary syndrome therapy.
- Published
- 2018
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