| http://purl.uniprot.org/citations/28692045 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/28692045 | http://www.w3.org/2000/01/rdf-schema#comment | "Epigenetic gene regulation linked to oncogenic pathways is an important focus of cancer research. KDM3A, a histone H3 lysine 9 (H3K9) demethylase, is known to have a pro-tumorigenic function. Here, we showed that KDM3A contributes to liver tumor formation through the phosphatidylinositol 3-kinase (PI3K) pathway, which is often activated in hepatocellular carcinoma. Loss of Kdm3a attenuated tumor formation in Pik3ca transgenic (Tg) mouse livers. Transcriptome analysis of pre-cancerous liver tissues revealed that the expression of activator protein 1 (AP-1) target genes was induced by PI3K activation, but blunted upon Kdm3a ablation. Particularly, the expression of Cd44, a liver cancer stem marker, was regulated by AP-1 in a Kdm3a-dependent manner. We identified Cd44-positive hepatocytes with epithelial-mesenchymal transition-related expression profiles in the Pik3ca Tg liver and confirmed their in vivo tumorigenic capacity. Notably, the number and tumor-initiating capacity of Cd44-positive hepatocytes were governed by Kdm3a. As a mechanism in Kdm3a-dependent AP-1 transcription, Kdm3a recruited c-Jun to the AP-1 binding sites of Cd44, Mmp7 and Pdgfrb without affecting c-Jun expression. Moreover, Brg1, a component of the SWI/SNF chromatin remodeling complex, interacted with c-Jun in a Kdm3a-dependent manner and was bound to the AP-1 binding site of these genes. Finally, KDM3A and c-JUN were co-expressed in 33% of human premalignant lesions with PI3K activation. Our data suggest a critical role for KDM3A in the PI3K/AP-1 oncogenic axis and propose a novel strategy for inhibition of KDM3A against liver tumor development under PI3K pathway activation."xsd:string |
| http://purl.uniprot.org/citations/28692045 | http://purl.org/dc/terms/identifier | "doi:10.1038/onc.2017.222"xsd:string |
| http://purl.uniprot.org/citations/28692045 | http://purl.uniprot.org/core/author | "Fujiwara H."xsd:string |
| http://purl.uniprot.org/citations/28692045 | http://purl.uniprot.org/core/author | "Kato M."xsd:string |
| http://purl.uniprot.org/citations/28692045 | http://purl.uniprot.org/core/author | "Kudo Y."xsd:string |
| http://purl.uniprot.org/citations/28692045 | http://purl.uniprot.org/core/author | "Nakagawa H."xsd:string |
| http://purl.uniprot.org/citations/28692045 | http://purl.uniprot.org/core/author | "Nakatsuka T."xsd:string |
| http://purl.uniprot.org/citations/28692045 | http://purl.uniprot.org/core/author | "Tanaka Y."xsd:string |
| http://purl.uniprot.org/citations/28692045 | http://purl.uniprot.org/core/author | "Takahashi R."xsd:string |
| http://purl.uniprot.org/citations/28692045 | http://purl.uniprot.org/core/author | "Yamamoto K."xsd:string |
| http://purl.uniprot.org/citations/28692045 | http://purl.uniprot.org/core/author | "Tachibana M."xsd:string |
| http://purl.uniprot.org/citations/28692045 | http://purl.uniprot.org/core/author | "Hirata Y."xsd:string |
| http://purl.uniprot.org/citations/28692045 | http://purl.uniprot.org/core/author | "Shinkai Y."xsd:string |
| http://purl.uniprot.org/citations/28692045 | http://purl.uniprot.org/core/author | "Sakai J."xsd:string |
| http://purl.uniprot.org/citations/28692045 | http://purl.uniprot.org/core/author | "Aburatani H."xsd:string |
| http://purl.uniprot.org/citations/28692045 | http://purl.uniprot.org/core/author | "Otsuka M."xsd:string |
| http://purl.uniprot.org/citations/28692045 | http://purl.uniprot.org/core/author | "Koike K."xsd:string |
| http://purl.uniprot.org/citations/28692045 | http://purl.uniprot.org/core/author | "Tateishi K."xsd:string |
| http://purl.uniprot.org/citations/28692045 | http://purl.uniprot.org/core/author | "Ijichi H."xsd:string |
| http://purl.uniprot.org/citations/28692045 | http://purl.uniprot.org/core/author | "Miyabayashi K."xsd:string |
| http://purl.uniprot.org/citations/28692045 | http://purl.uniprot.org/core/author | "Asaoka Y."xsd:string |
| http://purl.uniprot.org/citations/28692045 | http://purl.uniprot.org/core/date | "2017"xsd:gYear |
| http://purl.uniprot.org/citations/28692045 | http://purl.uniprot.org/core/name | "Oncogene"xsd:string |
| http://purl.uniprot.org/citations/28692045 | http://purl.uniprot.org/core/pages | "6262-6271"xsd:string |