C/EBPβ enhances platinum resistance of ovarian cancer cells by reprogramming H3K79 methylation

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作者：Liu Dan, Zhang Xiao-Xue, Li Meng-Chen, Cao Can-Hui, Wan Dong-Yi, Xi Bi-Xin, Tan Jia-Hong, Wang Ji, Yang Zong-Yuan, Feng Xin-Xia, Ye Fei, Chen Gang, Wu Peng, Xi Ling, Wang Hui, Zhou Jian-Feng, Feng Zuo-Hua, Ma Ding, Gao Qing-Lei
期刊：Nature Communications
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Chemoresistance is a major unmet clinical obstacle in ovarian cancer treatment. Epigenetics plays a pivotal role in regulating the malignant phenotype, and has the potential in developing therapeutically valuable targets that improve the dismal outcome of this disease. Here we show that a series of transcription factors, including C/EBPβ, GCM1, and GATA1, could act as potential modulators of histone methylation in tumor cells. Of note, C/EBPβ, an independent prognostic factor for patients with ovarian cancer, mediates an important mechanism through which epigenetic enzyme modifies groups of functionally related genes in a context-dependent manner. By recruiting the methyltransferase DOT1L, C/EBPβ can maintain an open chromatin state by H3K79 methylation of multiple drug-resistance genes, thereby augmenting the chemoresistance of tumor cells. Therefore, we propose a new path against cancer epigenetics in which identifying and targeting the key regulators of epigenetics such as C/EBPβ may provide more precise therapeutic options in ovarian cancer.