SATB1 regulates TXNIP inhibiting invasion and infiltration in T-cell acute lymphoblastic leukemia.

Abstract

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy with a poor prognosis. Thioredoxin-interacting protein (TXNIP), a key protein, binds to thioredoxin and acts as a tumor suppressor in multiple cancers. However, its specific functions and mechanisms in T-ALL remain unclear. Here, CCK-8 and Transwell assays were used to assess its proliferation and invasiveness, with findings validated in a murine leukemia model. 4D proteomics combined with bioinformatics analyses were applied to elucidate its role in DNA damage repair. Guided by CHIP-seq results, we further validated the regulatory axis between Special AT-rich sequence binding protein 1 (SATB1) and TXNIP, as well as their involvement in T-ALL invasion, using CHIP-PCR and rescue assays. Our data demonstrated low expression of TXNIP in T-ALL patients. TXNIP significantly inhibited the proliferation and invasiveness of T-ALL cells and was involved in DNA damage response by suppressing MRN complex (MRE11-RAD50-NBS1) expression. We also identified SATB1 as a transcriptional regulator of TXNIP in Jurkat cells. Notably, TXNIP overexpression counteracted the pro-invasive effects induced by SATB1 knockdown in Jurkat cells (P&#x2009;<&#x2009;0.05). In summary, TXNIP inhibits the proliferation and invasion of T-ALL, and impairs DNA damage repair processes. SATB1 positively regulates TXNIP, thereby suppressing the invasiveness of Jurkat cells.