ZNF460 enhances HADHB level by activating its transcription to promote the progression and pulmonary invasion of cutaneous T cell lymphoma.

BACKGROUND

During the progression of primary cutaneous T-cell lymphoma (CTCL), malignant T cells acquire the capacity to invade extracutaneous sites. However, the mechanisms driving CTCL progression and invasion remain poorly understood. This study aimed to investigate the role and specific mechanisms of ZNF460 and HADHB in the progression of CTCL.

METHODS

The viability, proliferation, apoptosis, migration, invasion, and fatty acid metabolism of malignant T lymphoma cells were assessed using CCK-8, EdU, TUNEL, Transwell, and ELISA assays. ChIP-qPCR, dual-luciferase reporter, qRT-PCR, and WB assays were utilized to elucidate the regulation of HADHB transcription by ZNF460. Tumor growth and pulmonary invasion in CTCL mouse models were evaluated through tumor growth curves and HE staining.

RESULTS

Knockdown of HADHB inhibited the viability, proliferation, migration, invasion, and fatty acid metabolism of malignant T lymphoma cells, whereas overexpression of HADHB exhibited the opposite effects. Furthermore, overexpression of HADHB accelerated the tumor growth rate and pulmonary invasion in CTCL mice. ZNF460 was found to upregulate HADHB levels in malignant T lymphoma cells by activating HADHB transcription. Additionally, knockdown of ZNF460 led to the reduction in viability, proliferation, and migration of malignant T lymphocytes and the inhibition of CTCL mice tumor growth and pulmonary invasion.

CONCLUSION

Collectively, ZNF460 enhanced HADHB levels by activating its transcription, thereby promoting CTCL tumor growth and pulmonary invasion.