Critical Role of lncEPAT in Coupling Dysregulated EGFR Pathway and Histone H2A Deubiquitination During Glioblastoma Tumorigenesis

Authors

Linlin Li
Aidong Zhou
Yanjun Wei
Feng Liu
Peng Li
Runping Fang
Li Ma
Sicong Zhang
Longqiang Wang
Jinze Liu
Hope T Richard
Yiwen Chen
Hengbin Wang
Suyun Huang

Publication Date

10-7-2022

Journal

Science Advances

Abstract

Histone 2A (H2A) monoubiquitination is a fundamental epigenetics mechanism of gene expression, which plays a critical role in regulating cell fate. However, it is unknown if H2A ubiquitination is involved in EGFR-driven tumorigenesis. In the current study, we have characterized a previously unidentified oncogenic lncRNA (lncEPAT) that mediates the integration of the dysregulated EGFR pathway with H2A deubiquitination in tumorigenesis. LncEPAT was induced by the EGFR pathway, and high-level lncEPAT expression positively correlated with the glioma grade and predicted poor survival of glioma patients. Mass spectrometry analyses revealed that lncEPAT specifically interacted with deubiquitinase USP16. LncEPAT inhibited USP16's recruitment to chromatin, thereby blocking USP16-mediated H2A deubiquitination and repressing target gene expression, including

Keywords

Carcinogenesis, Chromatin, Clusterin, ErbB Receptors, Glioblastoma, Histones, Humans, RNA, Long Noncoding, Ubiquitin Thiolesterase

DOI

10.1126/sciadv.abn2571

PMID

36197973

PMCID

PMC9534510

PubMedCentral® Posted Date

10-5-2022

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes