例如:"lncRNA", "apoptosis", "WRKY"

EZH2 targeting reduces medulloblastoma growth through epigenetic reactivation of the BAI1/p53 tumor suppressor pathway.

Oncogene. 2020 Jan;39(5):1041-1048. Epub 2019 Oct 03
{{ author.authorName }}{{getOrganisationIndexOf(author)}} {{ author.authorName }}{{getOrganisationIndexOf(author)}}
{{ author.authorName }}{{getOrganisationIndexOf(author)}} {{ author.authorName }}{{getOrganisationIndexOf(author)}}
+ et al

[No authors listed]

Author information
  • {{index+1}} {{ organisation }}

摘要


Medulloblastoma (MB) is a malignant pediatric brain tumor for which new therapies are urgently needed. We demonstrate that treatment with EPZ-6438 (Tazemetostat), an enhancer of zeste homolog 2 (EZH2) inhibitor approved for clinical trials, blocks MB cell growth in vitro and in vivo, and prolongs survival in orthotopic xenograft models. We show that the therapeutic effect is dependent on epigenetic reactivation of adhesion G-protein-coupled receptor B1 (BAI1/ADGRB1), a tumor suppressor that controls p53 stability by blocking Mdm2. Histone 3 trimethylated on lysine 27 (H3K27me3), a marker of silent chromatin conformation is present at the ADGRB1 promoter, and inhibition of EZH2, the catalytic component of the Polycomb Repressive complex 2 (PRC2) that methylates H3K27, switches the gene into an active chromatin status and reactivates BAI1 expression. Mechanistically, targeting EZH2 promotes transition from H3K27me3 to H3K27ac at the promoter, recruits the C/EBPβ (CREB-binding protein) and CBP transcription factors and activates ADGRB1 gene transcription. Taken together, our results identify key molecular players that regulate ADGRB1 gene expression in MB, demonstrate that reactivation of BAI1 expression underlies EPZ-6438 antitumorigenic action, and provide preclinical proof-of-principle evidence for targeting EZH2 in patients with MB.

KEYWORDS: {{ getKeywords(articleDetailText.words) }}

基因功能


  • {{$index+1}}.{{ gene }}

图表


原始数据


 保存测序数据
Sample name
Organism Experiment title Sample type Library instrument Attributes
{{attr}}
{{ dataList.sampleTitle }}
{{ dataList.organism }} {{ dataList.expermentTitle }} {{ dataList.sampleType }} {{ dataList.libraryInstrument }} {{ showAttributeName(index,attr,dataList.attributes) }}

文献解读