Histone arginine methyltransferase CARM1 selective inhibitor TP-064 induces apoptosis in endometrial cancer
Histone arginine methyltransferase CARM1 selective inhibitor TP-064 induces apoptosis in endometrial cancer
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DOI：
10.1016/j.bbrc.2022.02.086
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发表时间：
2022-03-01
影响因子：
3.1
通讯作者：
Osuga, Yutaka
中科院分区：
文献类型：
--
作者：
Inoue, Futaba;Sone, Kenbun;Osuga, Yutaka
组蛋白修饰是调控基因表达的关键表观遗传机制。辅活化型精氨酸甲基转移酶1(CARM1)是一种精氨酸甲基转移酶，它催化组蛋白H3(H3R17)在精氨酸17位发生二甲基化。最近发现CARM1与人类的癌变有关，CARM1的选择性抑制剂TP-064被证明是治疗多发性骨髓瘤的潜在药物。然而，CARM1在子宫内膜癌中的生理意义尚不清楚。因此，我们旨在探讨CARM1和TP064在子宫内膜癌中的作用。为此，我们利用实时定量聚合酶链式反应分析了CARM1在子宫内膜癌中的表达，并探讨了CARM1基因敲除子宫内膜癌细胞的抗肿瘤机制。此外，我们还评价了TP-064对子宫内膜癌细胞的治疗能力。CARM1在52例子宫内膜癌组织中的表达显著高于正常子宫内膜组织。CARM1基因敲除的子宫内膜癌细胞生长受到抑制，并诱导细胞凋亡。TP-064还抑制子宫内膜癌细胞生长，减少子宫内膜癌细胞集落数量。这些数据表明，CARM1可能是治疗子宫内膜癌的有效靶点。(C)2022爱思唯尔公司。保留所有权利。
Histone modification is the key epigenetic mechanism that regulates gene expression. Coactivatorassociated 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 TP064 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.(c) 2022 Elsevier Inc. All rights reserved.