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

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

Nature communications (2018-05-02)
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, Qing-Lei Gao
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-C/EBP-β antibody produced in rabbit, affinity isolated antibody
Sigma-Aldrich
SGC0946, ≥98% (HPLC)
Sigma-Aldrich
Anti-trimethyl-Histone H3 (Lys27) Antibody, Upstate®, from rabbit