Abstract
Epigenome regulates gene transcription in response to various extra- cellular stimuli in cells. The system is fine tuned by complex mechanisms including DNA methylation, histone modification, and chromatin structural change. Recent research identified genomic alterations in such epigenome regulatory factors and visualized the landscape of specific epigenomic status in several cancer cells, suggesting the role for epigenome in the initiation and progression of tumors including pancreatic malignancies. Though the critical roles of genetic mutations in pancreatic ductal adenocarcinoma have been well examined, these genetic alterations have not fully explained the complexity of tumor development, still suggesting the involvement of other factors including epigenome regulators. KDM6B is a histone modifying enzyme and has been proposed to be a tumor suppressor, since it activates p16/CDKN2A gene under oncogenic KRAS mutations, thereby inducing senescence in premalignant lesions. Here we showed a novel role for KDM6B-C/EBPα axis in the tumorigenesis of PDAC cells. Our findings emphasize that understandings of cancer epigenome develop a new possibility in targeting strategies against pancreatic tumors.
