Tripartite motif containing 24 regulates cell proliferation in colorectal cancer through YAP signaling

Abstract

The protein, tripartite motif containing 24 (TRIM24) is a member of the TRIM protein family, and acts as a critical co-regulator of multiple nuclear receptors. TRIM24 is dysregulated in many cancers, including colorectal carcinoma. However, its biological functions and molecular mechanisms with respect to colorectal carcinoma are still largely unknown. In the current study, we found that TRIM24 promotes YAP signaling for driving cell proliferation in colorectal cancer. TRIM24 was significantly upregulated in colorectal carcinoma, and its expression was negatively correlated with the survival of patients. Depletion of TRIM24 impaired the ability of the cancer cells to proliferate and form colonies. Furthermore, this study also revealed the mechanism underlying the recruitment of TRIM24 by the DANCR/KAT6A complex, which is bound to acetylated lysine 23 of histone H3 (H3K23), resulting in binding to the YAP promoter and activation of YAP transcription that ultimately enhances the proliferation of colorectal cancer cells. Our results revealed a novel mechanism involving TRIM24-YAP signaling for the regulation of colorectal cancer. We also identified TRIM24 as a potential therapeutic molecule for targeting colorectal cancer.