Cargando…

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

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5928165/
https://www.ncbi.nlm.nih.gov/pubmed/29712898
http://dx.doi.org/10.1038/s41467-018-03590-5
Descripción
Sumario: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.