Carcinogenesis promotion in oral squamous cell carcinoma: KDM4A complex-mediated gene transcriptional suppression by LEF1.

ABSTRACT

Oral squamous cell carcinoma (OSCC) is the most prevalent cancer of the mouth, characterised by rapid progression and poor prognosis. Hence, an urgent need exists for the development of predictive targets for early diagnosis, prognosis determination, and clinical therapy. Dysregulation of lymphoid enhancer-binding factor 1 (LEF1), an important transcription factor involved in the Wnt-ß-catenin pathway, contributes to the poor prognosis of OSCC. Herein, we aimed to explore the correlation between LEF1 and histone lysine demethylase 4 A (KDM4A). Results show that the KDM4A complex is recruited by LEF1 and specifically binds the LATS2 promoter region, thereby inhibiting its expression, and consequently promoting cell proliferation and impeding apoptosis in OSCC. We also established NOD/SCID mouse xenograft models using CAL-27 cells to conduct an in vivo analysis of the roles of LEF1 and KDM4A in tumour growth, and our findings show that cells stably suppressing LEF1 or KDM4A have markedly decreased tumour-initiating capacity. Overall, the results of this study demonstrate that LEF1 plays a pivotal role in OSCC development and has potential to serve as a target for early diagnosis and treatment of OSCC.