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

• Published in: Biochemical and biophysical research communications Vol. 601; pp. 123 - 128
• Main Authors: Inoue, Futaba, Sone, Kenbun, Toyohara, Yusuke, Tanimoto, Saki, Takahashi, Yu, Kusakabe, Misako, Kukita, Asako, Honjoh, Harunori, Nishijima, Akira, Taguchi, Ayumi, Miyamoto, Yuichiro, Tanikawa, Michihiro, Iriyama, Takayuki, Uchino, Mayuyo-mori, Tsuruga, Tetsushi, Wada-Hiraike, Osamu, Oda, Katsutoshi, Osuga, Yutaka
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 23.04.2022
• Subjects: Apoptosis; Arginine - metabolism; CARD Signaling Adaptor Proteins; CARM1; Endometrial cancer; Endometrial Neoplasms - drug therapy; Endometrial Neoplasms - genetics; Female; Guanylate Cyclase; Histone arginine methyltransferase; Histones - metabolism; Humans; Intracellular Signaling Peptides and Proteins; Methylation; Protein-Arginine N-Methyltransferases - genetics; Protein-Arginine N-Methyltransferases - metabolism; TP-064; Histone arginine methyltransferase; Endometrial cancer; CARM1; PRMT; TP-064; EC; HMT; Apoptosis
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2022.02.086

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. •CAMR1 was significantly overexpressed in 52 endometrial cancer tissues.•CARM1-knockdown suppressed endometrial cancer cell growth and induced apoptosis.•A selective inhibitor of CARM1 TP-064 suppressed endometrial cancer cell growth.