Histone arginine methyltransferase CARM1 selective inhibitor TP-064 induces apoptosis in endometrial cancer

Abstract

Histone modification is the key epigenetic mechanism that regulates gene expression. Coactivator-associated arginine methyltransferase 1 (CARM1) is an arginine methyltransferase that catalyzes dimethylation of histone H3 (H3R17) at arginine 17. Lately, it has been suggested that CARM1 is associated with human carcinogenesis, and the CARM1-selective inhibitor, TP-064, has been shown to be a potential therapeutic agent for multiple myeloma. However, the physiological significance of CARM1 in endometrial cancer remains unclear. Therefore, we aimed to explore the role of CARM1 and the effect of TP-064 in endometrial cancer. To this end, we analyzed CARM1 expression in endometrial cancer using quantitative real-time polymerase chain reaction and examined the antitumor mechanism with CARM1 knockdown endometrial cancer cells. Moreover, we evaluated the therapeutic capability of TP-064 in endometrial cancer cells. CARM1 was remarkably overexpressed in 52 endometrial cancer tissues compared to normal endometrial tissues. The growth of CARM1 knockdown endometrial cancer cells was suppressed and CARM1 knockdown induced apoptosis. TP-064 also inhibited endometrial cancer cell growth and declined the number of endometrial cancer cell colonies. These data suggest that CARM1 may be a powerful therapeutic target for endometrial cancer.

Keywords: Apoptosis; CARM1; Endometrial cancer; Histone arginine methyltransferase; TP-064.