TRPS1 inhibits cervical cancer progression by suppressing ORC6-mediated tumor stemness

Cervical cancer remains a major cause of cancer-related morbidity and mortality in women, particularly among patients diagnosed with locally advanced, recurrent, or metastatic disease. Here, we investigated the role of transcriptional repressor GATA-binding 1 (TRPS1) in cervical cancer progression and defined its downstream regulatory mechanism. Bioinformatics analysis revealed differential expression of TRPS1 between cervical cancer and normal cervical tissues. To further explore its functional role, TRPS1 was overexpressed in cervical cancer cell lines via lentiviral infection. In vitro and in vivo experiments confirmed that TRPS1 expression was downregulated in cervical cancer, and its overexpression inhibited cervical cancer cell proliferation, migration, invasion, and stemness, as well as tumor growth in xenograft models. Mechanistically, ORC6 was identified as a candidate downstream effector of TRPS1. TRPS1 bound to the ORC6 promoter and repressed ORC6 transcription, leading to reduced ORC6 expression. Functional rescue experiments showed that ORC6 restoration partially reversed TRPS1-mediated inhibition of cell-cycle progression, apoptosis resistance, stemness-marker expression, EMT-associated marker expression, and tumor growth. Notably, low TRPS1 expression and high ORC6 expression were associated with lymphovascular invasion and lymph node metastasis in cervical cancer patients. Together, these findings identify a TRPS1-ORC6 regulatory axis that restrains cervical cancer stemness and progression.