SNF5 deficiency induces apoptosis resistance by repressing SATB1 expression in Sézary syndrome

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.

KEYWORD:

• SNF5
• SATB1
• Sézary syndrome
• apoptosis resistance

Acknowledgements

We thank Dr. Xudong Wu from Tianjin Medical University, Dr. Charlie Roberts form St. Jude Children’s Hospital for reagents, helpful discussions and comments. We also are greatly grateful to Dr. Jonathan D. Leavenworth for language editing.

Potential conflict of interest

Disclosure forms provided by the authors are available with the full text of this article online at https://doi.org/10.1080/10428194.2017.1422861.

Additional information

Funding

This work was supported by the Ministry of Science and Technology of the People's Republic of China, [grant# 2014CB910100 to X. W. and J. Y.], and the National Natural Science Foundation of China, [grants# 81171899 and 81372230 to X. W.; grant# 31600705 to J. Y.; grant# 31600693 to Z. L.; and grant# 81770213 to H. Z.].