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

Author

Listed:
  • 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)

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.

Suggested Citation

  • 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, 2018. "C/EBPβ enhances platinum resistance of ovarian cancer cells by reprogramming H3K79 methylation," Nature Communications, Nature, vol. 9(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-03590-5
    DOI: 10.1038/s41467-018-03590-5
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