摘要
Histone deacetylases (HDACs) have been linked to a variety of cancers, and HDAC inhibitors (HDACi) are a promising class of drugs that have demonstrated anti-cancer effects. However, we have little knowledge regarding the selection and application of HDAC inhibitors to the personalized treatment of ovarian cancer (OC). Here, we report a correlation between the high expression of HDACs and poor outcomes in OC patients, which reveals that HDACi are a class of agents that show great promise for the treatment of OC. Furthermore, we found that HDACi increased both the mRNA and protein levels of DHRS2, which has been shown to be closely linked to HDACi sensitivity when it is highly expressed, especially in ovarian cancer cells. Consistently, we found that suppression of DHRS2 reduced the sensitivity of OC cells to HDAC inhibitors via attenuation of the inhibitory effects of HDAC inhibitors on Mcl-1 in vitro. Our study demonstrated that DHRS2 expression was decreased in OC tissues and that high expression of DHRS2 was correlated with better outcomes in OC patients. In addition, DHRS2 expression was closely related to the effects of chemotherapy. Our study reveals the role of DHRS2 in cell apoptosis induced by HDAC inhibitors and explores the clinical attributes of DHRS2 in OC from a new perspective, suggesting that OC patients with high DHRS2 expression may benefit from treatment with HDAC inhibitors.
摘要译文
组蛋白脱乙酰基酶（HDACs）与多种癌症有关，HDAC抑制剂（HDACi）是一类有前途的药物，已显示出抗癌作用。但是，我们对HDAC抑制剂的选择和在卵巢癌（OC）个性化治疗中的应用知之甚少。在这里，我们报道了OC患者中HDAC的高表达与不良预后之间的相关性，这表明HDACi是一类对OC的治疗具有广阔前景的药物。此外，我们发现HDACi会增加DHRS2的mRNA和蛋白质水平，这已被证明与HDACi的高表达密切相关，尤其是在卵巢癌细胞中。一致地，我们发现DHRS2的抑制通过减弱HDAC抑制剂对Mcl-1的体外抑制作用而降低了OC细胞对HDAC抑制剂的敏感性。我们的研究表明，OCRS组织中DHRS2表达降低，而OCRS患者中DHRS2的高表达与更好的预后相关。另外，DHRS2的表达与化疗效果密切相关。我们的研究揭示了DHRS2在HDAC抑制剂诱导的细胞凋亡中的作用，并从一个新的角度探讨了OCRS中DHRS2的临床特征，表明DHRS2表达高的OC患者可能受益于HDAC抑制剂的治疗。
Yingyan Han; Zhi Wang; Shujuan Sun; Zeyu Zhang; Jia Liu; Xin Jin; Peng Wu; Teng Ji; Wencheng Ding; Beibei Wang ; Qinglei Gao. Decreased DHRS2 expression is associated with HDACi resistance and poor prognosis in ovarian cancer[J]. Epigenetics, 2020,15(1-2): 122-133