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

Dan Liu, Xiao-Xue Zhang, Meng-Chen Li, Can-Hui Cao, Dong-Yi Wan, Bi-Xin Xi, Jia-Hong Tan, Ji Wang, Zong-Yuan Yang, Xin-Xia Feng, Fei Ye, Gang Chen, Peng Wu, Ling Xi, Hui Wang, Jian-Feng Zhou, Zuo-Hua Feng, Ding Ma and Qing-Lei Gao ()
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Dan Liu: Huazhong University of Science and Technology
Xiao-Xue Zhang: Huazhong University of Science and Technology
Meng-Chen Li: Huazhong University of Science and Technology
Can-Hui Cao: Huazhong University of Science and Technology
Dong-Yi Wan: Huazhong University of Science and Technology
Bi-Xin Xi: Huazhong University of Science and Technology
Jia-Hong Tan: Huazhong University of Science and Technology
Ji Wang: Huazhong University of Science and Technology
Zong-Yuan Yang: Huazhong University of Science and Technology
Xin-Xia Feng: Huazhong University of Science and Technology
Fei Ye: Huazhong University of Science and Technology
Gang Chen: Huazhong University of Science and Technology
Peng Wu: Huazhong University of Science and Technology
Ling Xi: Huazhong University of Science and Technology
Hui Wang: Huazhong University of Science and Technology
Jian-Feng Zhou: Huazhong University of Science and Technology
Zuo-Hua Feng: Huazhong University of Science and Technology
Ding Ma: Huazhong University of Science and Technology
Qing-Lei Gao: Huazhong University of Science and Technology

Nature Communications, 2018, vol. 9, issue 1, 1-13

Abstract: Abstract 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.

Date: 2018
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DOI: 10.1038/s41467-018-03590-5

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