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Histone demethylase KDM4C controls tumorigenesis of glioblastoma by epigenetically regulating p53 and c-Myc

Authors
 Dong Hoon Lee  ;  Go Woon Kim  ;  Jung Yoo  ;  Sang Wu Lee  ;  Yu Hyun Jeon  ;  So Yeon Kim  ;  Hyeok Gu Kang  ;  Da-Hyun Kim  ;  Kyung-Hee Chun  ;  Junjeong Choi  ;  So Hee Kwon 
Citation
 CELL DEATH & DISEASE, Vol.12(1) : 89, 2021-01 
Journal Title
 CELL DEATH & DISEASE 
Issue Date
2021-01
Abstract
Glioblastoma is the most lethal brain tumor and its pathogenesis remains incompletely understood. KDM4C is a histone H3K9 demethylase that contributes to epigenetic regulation of both oncogene and tumor suppressor genes and is often overexpressed in human tumors, including glioblastoma. However, KDM4C's roles in glioblastoma and the underlying molecular mechanisms remain unclear. Here, we show that KDM4C knockdown significantly represses proliferation and tumorigenesis of glioblastoma cells in vitro and in vivo that are rescued by overexpressing wild-type KDM4C but not a catalytic dead mutant. KDM4C protein expression is upregulated in glioblastoma, and its expression correlates with c-Myc expression. KDM4C also binds to the c-Myc promoter and induces c-Myc expression. Importantly, KDM4C suppresses the pro-apoptotic functions of p53 by demethylating p53K372me1, which is pivotal for the stability of chromatin-bound p53. Conversely, depletion or inhibition of KDM4C promotes p53 target gene expression and induces apoptosis in glioblastoma. KDM4C may serve as an oncogene through the dual functions of inactivation of p53 and activation of c-Myc in glioblastoma. Our study demonstrates KDM4C inhibition as a promising therapeutic strategy for targeting glioblastoma.
Files in This Item:
T202100274.pdf Download
DOI
10.1038/s41419-020-03380-2
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
Yonsei Authors
Kang, Hyeok Gu(강혁구) ORCID logo https://orcid.org/0000-0002-3187-6844
Chun, Kyung Hee(전경희) ORCID logo https://orcid.org/0000-0002-9867-7321
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/182042
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