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<p>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 (<i>P</i> &lt; 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.</p>

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

  • 期刊论文

  • 发表日期：

    2025年10月22日

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  • Lang He,
  • Huo Tan,
  • Anqiao Li,
  • Runhui Zheng,
  • Danyun Yuan,
  • Yimin Chen,
  • Shuyi Chen,
  • Jiaoyuan Qin,
  • Li Tan,
  • Sida Peng,
  • Zhenqian Huang,
  • Lihua Xu

摘要

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 < 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.