Transcription factor EMX2 functions as a tumor suppressor in renal cell carcinoma by targeting CADM1 and PI3K-AKT sig-naling

Renal cell carcinoma (RCC) is one of the most common tumors of the urinary system. However, the development and migration mechanism of RCC remains largely unknown. In this study, we find that EMX2 is significantly downregulated in RCC biopsy and cell lines compared to that in adja-cent non-tumor tissues and normal cell lines. The expression of EMX2 is closely associated with the prognosis of RCC patients. EMX2 is proved to restrain cell proliferation, migration, and invasion of RCC cells, acting as a tumor suppressor. Importantly, EMX2 promotes RCC cell apoptosis and in-hibits xenografted tumor growth in mice. We performed RNA sequencing (RNA-seq) and chro-matin immunoprecipitation sequencing (ChIP-seq) in EMX2-overexpressed RCC cells and control cells, and identified downstream targets and signaling pathways that are regulated by EMX2. Mechanistically, EMX2 binds to the promoter of CADM1 and activates its transcription, which impedes PI3K-AKT signaling, leading to inhibition of renal tumor growth. Our studies establish the tumor suppressor function of EMX2-CADM1 axis in RCC, thus providing novel insights into potential therapeutic intervention in renal malignancy.