KLF12-mediated suppression of androgen receptor accelerates metastasis in endometrioid endometrial carcinoma by activating epithelial-mesenchymal transition.

For patients with advanced endometrioid endometrial carcinoma (EEC), prognosis remains poor due to the lack of effective therapeutic targets. Loss of androgen receptor (AR) expression is associated with the progression of EEC. However, the regulatory mechanisms remain unknown, limiting its application in prognostic prediction and targeted therapy. In this study, overexpression of KLF12 or loss of AR was strongly correlated with advanced clinical stage and poor patient outcomes. Functional experiments demonstrated that KLF12 upregulation suppressed AR expression and promoted EEC metastasis by enhancing epithelial-mesenchymal transition (EMT) both in vitro and in vivo. As determined by bioinformatics predictions and CUT&Tag analysis, KLF12 suppressed the transcriptional activity of the AR gene by binding to the promoter and intronic regions. These direct interactions were further confirmed through electrophoretic mobility shift assay (EMSA), ChIP-PCR, ChIP-qPCR and dual-luciferase reporter assays. This study identifies a novel KLF12-AR regulatory axis driving EEC metastasis and provides potential molecular targets for therapeutic intervention and prognostic evaluation.